Trial summary

The purpose of this study is to determine whether or not treating patients with cisplatin and gemcitabine chemotherapy helps reduce the risk of cancer returning. 
Who is it for?
ACTICCA-1 is a clinical research study for people who have a cancer of the biliary tract (cancer of the gall bladder or bile duct, also known as cholangiocarcinoma in medical terms) which has been removed in an operation.
Study details
These drugs are being tested as they have been shown to be the most effective chemotherapy combination in more advanced cases of biliary tract cancer, where the disease is inoperable or has spread to other areas of the body.
This is an international investigator initiated study called ACTICCA-1, which is being led by the University Medical Centre Hamburg- Eppendorf in Germany and conducted in Australia by the Australasian Gastro-Intestinal Trials Group (AGITG) in collaboration with the National Health and Medical Research Centre Clinical Trials Centre (NHMRC CTC), University of Sydney.
The study involves randomly allocating participants to receive either chemotherapy with cisplatin and gemcitabine or the current standard of care (capecitabine). The drugs used in this study are approved in Australia to treat various cancers, however they do not have a specific listing by the Australian Therapeutics Goods Administration (TGA) for biliary tract cancer
The total duration of the study is 5 years. 
It is hoped that the findings of this study will provide details on whether giving cisplatin and gemcitabine chemotherapy following surgery for cancer of the biliary tract is a safe and effective treatment to reduce the chance of disease progression and increase survival time and quality of life.

Broad Health Conditioncholangiocarcinoma
muscle invasive gallbladder carcinoma

Specific Health ConditionCancer
Biliary tree (gall bladder and bile duct)

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,QLD,SA,WA

Hospital
Bankstown-Lidcombe Hospital - Bankstown

Hospital
Royal Brisbane & Womens Hospital - Herston

Hospital
Flinders Medical Centre - Bedford Park

Hospital
Nepean Hospital - Kingswood

Hospital
Calvary Mater Newcastle - Waratah

Hospital
The Townsville Hospital - Douglas

Hospital
Prince of Wales Hospital - Randwick

Hospital
Princess Alexandra Hospital - Woolloongabba

Hospital
Sir Charles Gairdner Hospital - Nedlands

Hospital
St John of God Hospital, Subiaco - Subiaco

Hospital
St George Hospital - Kogarah

Hospital
Fiona Stanley Hospital - Murdoch

Postcode
2747 - Kingswood

Postcode
2298 - Waratah

Postcode
4814 - Douglas

Postcode
2031 - Randwick

Postcode
4102 - Woolloongabba

Postcode
6009 - Nedlands

Postcode
6008 - Subiaco

Postcode
2217 - Kogarah

Postcode
6150 - Murdoch

Trial location outside Australia

Country
Germany

Country
Netherlands

Country
United Kingdom

Anticipated date of first participant enrolment1/12/2015

Anticipated date of last participant enrolment1/09/2020

Phase of TrialPhase 3

Has the study received ethics approval?Approved

Key inclusion criteria

* Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumour entities (HCC/CCA) are excluded)
* Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy
*ECOG 0-1
*Age greater than 18 years
* Adequate hematologic function: ANC greater than or equal to 1.5 x 10*9/L, platelets greater than or equal to 100 x 10*9/L, haemoglobin greater than or equal to 9 grams/dl or greater than or equal to 5.59 mmol/L
* Adequate liver function as measured by serum transaminases (AST and ALT) less than or equal to 5xULN and bilirubin less than or equal to 3xULN
*Adequate renal function, ie. serum creatinine less than or equal to 1.5xULN, glomerular filtration rate greater than or equal to 60mL/min (MDRD)
* No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy
* No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomisation
* Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women less than 1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7 day window be exceeded)
* Written informed consent

Minimum age18 Years

GenderBoth males and females

Can Healthy volunteers participate?No

Key exclusion criteria

* Prior chemotherapy for biliary tract cancer
* Previous malignancy within 3 years or concomitant malignancy, except: those with a 5 year overall survival rate of more than 90% e.g non-melanomatous skin cancer or adequately treated in-situ cervical cancer 
* Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia
* Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
* Serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial
* Fertile women (less than 1 year after last menstruation) and procreative men unwilling and unable to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
* Pregnancy or lactation

Trial summary

This is a multi-center, open-label, dose escalation study to determine the safety,
tolerability, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of
QBS10072S in patients with advanced or metastatic cancers with high LAT1 expression. The MTD
of QBS10072S will be confirmed in patients with relapsed or refractory grade 4 astrocytoma.

Broad Health ConditionPhase 1
Dose escalation
Metastatic
Brain metastasis
Brain metastases
GBM
Astrocytoma
Brain tumor
Cancer
Oncology
Glioblastoma
Glioblastoma multiforme
Brain
Neurology
Neuroscience
Headaches
Vomiting
Seizures
Drowsiness
Chemotherapy
Surgery
Radiation
Neuro-oncology
Blurred vision
Loss of appetite
Speech difficulty
Changes in ability to think and learn
Changes in mood and personality
Persistent headaches
Neuropathologist
Magnetic resonance spectroscopy (MRS)
Positron emission tomography (PET scan)
Intraoperative MRI
Tumor removal
Craniotomy
Standard external beam radiation therapy
Radiosurgery
Temozolomide
Bevacizumab
Avastin
Neurological exam
TMZ

Specific Health ConditionCancer
Astrocytoma
Brain Cancer
Brain Metastases
Bladder Cancer
Breast Cancer
Cervical Cancer
Cholangiocarcinoma
Colorectal Cancer
Esophagus Cancer
Gastric Cancer
Head and Neck Cancer
Kidney Cancer
Liver Cancer
Lung Cancer
Melanoma
Ovarian Cancer
Pancreatic Cancer
Pleural Mesothelioma
Prostate Cancer
Sarcoma
Tongue Cancer
Thymic Carcinoma
Urinary Tract Cancer

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,

Hospital
St George Private Hospital

Hospital
Sydney Southwest Private Hospital

Anticipated date of first participant enrolment1/07/2020

Phase of TrialPhase 1

Key inclusion criteria

Inclusion Criteria:

    1. Male or female participants aged =18 years at the time of informed consent.

    2. Adequate Bone Marrow Function

    3. Adequate renal function

    4. Adequate Liver Function

    5. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade =1
       except for AEs not constituting a safety risk by Investigator judgment.

    6. A histological or cytological diagnosis of a solid tumor that is advanced/metastatic,
       patients intolerant to standard treatment or, resistant to standard therapy* (per NCCN
       guidelines) or for which no curative therapy is available for the following tumor
       types:

       - Bladder, Brain, Breast, Cervical, Cholangiocarcinoma, Colorectal, Esophageal,
       Gastric, Head and Neck, Kidney, Liver, Lung, Melanoma, Ovarian, Pancreatic, Pleural
       mesothelioma, Prostate, Sarcoma, Tongue cancer, Thymic carcinomas, Urinary tract

    7. At least one measurable lesion (as defined by RECIST version 1.1) that has not been
       previously irradiated.

    8. An ECOG PS 0 to 2.

  Exclusion Criteria:

    1. Patients with tumor primarily localized to the brainstem or spinal cord. Presence of
       known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or
       leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or
       progressive growth.

    2. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of
       life-threatening complications in the short term (including patients with massive
       uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and
       over 50% liver involvement).

    3. Patients with any other active malignancy within 3 years prior to enrollment, except
       for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.

    4. Major surgery within 4 weeks prior to study entry.

    5. Radiation therapy within 4 weeks prior to receiving the first QBS10072S dose (bone
       lesions requiring radiation may be treated with limited radiation therapy during this
       period).

    6. Systemic anticancer therapy within 4 weeks prior to study entry

    7. Bleeding esophageal or gastric varices <2 months prior to the date of informed
       consent.

    8. Unmanageable ascites.

    9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may
       affect patient safety or interpretation of study results

   10. On therapeutic anticoagulation, except low molecular weight heparin, vitamin K
       antagonists or factor Xa inhibitors may be allowed following discussion with the
       Sponsor.

   11. Any of the following in the previous 6 months: myocardial infarction, congenital long
       QT syndrome, Torsade de Pointes, clinically significant arrhythmias (including
       sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior
       hemiblock, bifascicular block, unstable angina, coronary/peripheral artery bypass
       graft, symptomatic congestive heart failure (New York Heart Association class III or
       IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary
       embolism or other clinical significant episode of thromboembolic disease. Ongoing
       cardiac dysrhythmias of NCI CTCAE Grade =2, atrial fibrillation of any grade (Grade =2
       in the case of asymptomatic lone atrial fibrillation).

   12. Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal
       medical therapy) or requiring more than two medications for adequate control.

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

NuTide:121 compares NUC-1031 with gemcitabine, both in combination with cisplatin, in
patients with previously untreated advanced biliary tract cancer.

The primary hypotheses are:

  -  The combination of NUC-1031 plus cisplatin prolongs overall survival compared to the
     gemcitabine plus cisplatin standard of care

  -  The combination of NUC-1031 plus cisplatin increases overall response rate compared to
     the gemcitabine plus cisplatin standard of care

Broad Health ConditionAdenocarcinoma
Ampullary
Antineoplastic Agents
Biliary Tract Cancer
Chemotherapy
Cholangiocarcinoma
Cisplatin
Digestive System Neoplasms
Distal Bile Duct
Extrahepatic
First-line Chemotherapy
Gallbladder
Gastrointestinal
Gemcitabine
Hepatobiliary
Intrahepatic
Locally advanced
Metastatic
Neoplasm
NUC-1031
ProTides
Untreated

Specific Health ConditionCancer
Biliary Tract Cancer

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,QLD,VIC,WA,

Hospital
St George Hospital

Hospital
Newcastle Private Hospital

Hospital
Westmead Hospital

Hospital
The Alfred Hospital

Hospital
Fiona Stanley Hospital

Hospital
Sir Charles Gairdner Hospital

Phase of TrialPhase 3

Key inclusion criteria

Inclusion Criteria:

    1. Written informed consent and authorization to use and disclose health information.

    2. Ability to comprehend and willingness to comply with the requirements of this
       protocol, including the QoL questionnaires.

    3. Female or male patients aged =18 years.

    4. Histologically- or cytologically-confirmed adenocarcinoma of the biliary tract
       (including gallbladder, intra and extra-hepatic biliary ducts and ampullary cancers)
       that is locally advanced, unresectable or metastatic. Patients with measurable (as per
       RECIST v1.1 criteria) or non-measurable disease are permitted.

    5. Life expectancy =16 weeks.

    6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

    7. Adequate biliary drainage with no evidence of ongoing infection. If applicable,
       treatable and clinically-relevant biliary duct obstruction has been relieved by
       internal endoscopic drainage/stenting at least 2 weeks previously or by palliative
       bypass surgery or percutaneous drainage prior to study treatment, and the patient has
       no active or suspected uncontrolled infection. Patients fitted with a biliary stent
       should be clinically stable and free of signs of infection for =2 weeks prior to study
       treatment. Patients with improving biliary function who meet all other inclusion
       criteria may be re-tested during the screening window.

    8. Adequate bone marrow, hepatic, and renal function, as evidenced by:

         -  Absolute neutrophil count (ANC) =1,500/µL without colony-stimulating factor
            support

         -  Platelet count =100,000/µL

         -  Haemoglobin =10 g/dL without need for haematopoietic growth factor or transfusion
            support in prior 2 weeks

         -  Total bilirubin <2 × upper limit of normal (ULN); does not apply to patients with
            Gilbert's syndrome. Consistent with inclusion criterion 7, patients whose whole
            bilirubin and biliary function is recovering may be re-tested during the
            screening period.

         -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) <5 × ULN

         -  Creatinine clearance =45 mL/min actual or calculated by the Cockcroft-Gault
            method

         -  International normalized ratio (INR) <1.5 and partial thromboplastin time (PTT)
            <1.5 × ULN; does not apply to patients on an anti-coagulant with stable dose 28
            days prior to first dose.

    9. QTc interval <450 msec (males) or <470 msec (females), in the absence of bundle branch
       block. In the presence of bundle branch block with consequent QTc prolongation,
       patients may be enrolled based on a careful risk-benefit assessment.

   10. Human Immunodeficiency Virus-infected patients who are healthy and have a low risk of
       Acquired Immunodeficiency Syndrome-related outcomes may be included in this study.

   11. Female patients of child-bearing potential (i.e., all women except those who are
       post-menopausal for =1 year or who have a history of hysterectomy or surgical
       sterilization) must have a negative pregnancy test within 3 days prior to the first
       study drug administration. All patients of child-bearing potential must agree to
       practice true abstinence or to use two highly effective forms of contraception, one of
       which must be a barrier method of contraception, from the time of screening until 6
       months after the last dose of study medication.

   12. Male patients with a female partner must either have had a successful vasectomy or
       they and their female partner meet the criteria above (not of childbearing potential
       or practicing highly effective contraceptive methods).

  Exclusion Criteria:

    1. Combined or mixed hepatocellular/cholangiocarcinoma.

    2. Prior systemic therapy for advanced or metastatic biliary tract cancer. However, prior
       chemotherapy in the adjuvant setting or low-dose chemotherapy given in conjunction
       with radiotherapy in the adjuvant setting and completed at least 6 months prior to
       enrolment is permitted. The following prior interventions are allowed provided the
       patient has fully recovered:

         -  Surgery: non-curative resection with macroscopic residual disease or palliative
            bypass surgery. Patients who have previously undergone curative surgery must now
            have evidence of non-resectable disease requiring systemic chemotherapy.

         -  Radiotherapy: prior radiotherapy (with or without radio-sensitizing low-dose
            chemotherapy) for localized disease and there is now clear evidence of disease
            progression requiring systemic chemotherapy.

         -  Photodynamic therapy: prior photodynamic therapy for localized disease with no
            evidence of metastatic disease or for localized disease to relieve biliary
            obstruction in the presence of metastatic disease provided there is now clear
            evidence of disease progression requiring systemic chemotherapy.

         -  Palliative radiotherapy: palliative radiotherapy provided that all adverse events
            have resolved and the patient has measurable disease outside the field of
            radiation.

    3. Prior treatment with or known hypersensitivity to NUC-1031, gemcitabine, cisplatin or
       other platinum-based agents or history of allergic reactions attributed to the
       excipients contained in NUC-1031 or diluent solution (dimethylacetamide [DMA],
       Kolliphor ELP, Tween 80).

    4. Symptomatic central nervous system or leptomeningeal metastases.

    5. History of other malignancies, except adequately treated non-melanoma skin cancer,
       curatively treated in situ cancer of the cervix, low grade prostate cancer not
       requiring treatment or other solid tumours curatively treated with no evidence of
       disease for =3 years.

    6. Concurrent serious (as deemed by the Investigator) medical conditions, including, but
       not limited to, New York Heart Association class III or IV congestive heart failure,
       history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis
       B or C, or other co-morbid conditions that in the opinion of the Investigator would
       impair study participation or cooperation.

    7. Congenital or acquired immunodeficiency (e.g., serious active infection with HIV). As
       per inclusion criterion 10, patients with HIV who are healthy and have a low risk of
       AIDS related outcomes are eligible.

    8. Other acute or chronic medical, neurological, or psychiatric condition or laboratory
       abnormality that may increase the risk associated with study participation or
       investigational product administration or may interfere with the interpretation of
       study results and, in the judgment of the investigator, would make the patient
       inappropriate for entry into this study.

    9. Prior exposure to another investigational agent within 28 days prior to randomization.

   10. Major surgery within 28 days prior to randomization; patient must have completely
       recovered from any prior surgical or other procedures.

   11. Pregnant or breastfeeding.

   12. Residual toxicities from prior treatments or procedures which have not regressed to
       Grade =1 severity (CTCAE v5.0), except for alopecia or = Grade 2 peripheral
       neuropathy.

   13. Concomitant use of drugs at doses known to cause clinically relevant prolongation of
       QT/QTc interval.

   14. Administration of a live vaccination within 28 days prior to randomization.

   15. Ongoing or recent (=6 months) hepatorenal syndrome.

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

Study consists of an open-label, safety run-in part and a randomized, double-blind,
placebo-controlled Phase 2/3 part. In the Phase 2/3 part, the study will evaluate whether
bintrafusp alfa in combination with the current standard of care (SoC) (gemcitabine plus
cisplatin) improves overall survival (OS) in chemotherapy and immunotherapy-naïve
participants with locally advanced or metastatic BTC compared to placebo, gemcitabine and
cisplatin.

Broad Health ConditionMetastatic Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder Cancer
Ampullary cancer
M7824
Bintrafusp alfa
Transforming growth factor-beta
Programmed death-ligand 1
INTR@PID

Specific Health ConditionCancer
Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder Cancer

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,QLD,VIC,

Hospital
Blacktown Hospital - PARENT

Phase of TrialPhase 2/Phase 3

Key inclusion criteria

Inclusion Criteria:

    -  Are participants with histologically or cytologically confirmed locally advanced or
       metastatic BTC

    -  Participants must have available tumor tissue (primary or metastatic) (archival or
       fresh biopsies) before the first administration of study treatment

    -  At least 1 measurable lesion according to RECIST 1.1

    -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study
       entry and at Week 1, Day 1 prior to dosing

    -  Life expectancy of >= 12 weeks, as judged by the Investigator

    -  Adequate hematological function, hepatic function, renal function, coagulation
       function as defined in the protocol

    -  Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be
       treated and on a stable dose of antivirals

    -  Other protocol defined inclusion criteria could apply

  Exclusion Criteria:

    -  Previous and/or intercurrent cancers

    -  Receipt of any organ transplantation, including allogeneic stem-cell transplantation,
       but with the exception of transplants that do not require immunosuppression

    -  Participants with symptomatic central nervous system (CNS) metastases

    -  Significant acute or chronic infection including known history of positive test for
       human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary
       infection and active bacterial or fungal infection requiring systemic therapy

    -  Active autoimmune disease that might deteriorate when receiving an immunostimulatory
       agent

    -  History of or concurrent interstitial lung disease

    -  History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent
       (within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease

    -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
       requiring hospitalization or precluding study therapy within 30 days before
       randomization

    -  Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune
       checkpoints)

    -  Other protocol defined exclusion criteria could apply

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

Infigratinib is an oral drug which selectively binds to fibroblast growth factor receptor
(FGFR) 2 and is being developed to treat participants with FGFR2 mutated cholangiocarcinoma.
The purpose of the study is to evaluate the efficacy and safety of the investigational agent
oral infigratinib vs standard of care chemotherapy (gemcitabine plus cisplatin) in first-line
treatment of participants with unresectable locally advanced or metastatic cholangiocarcinoma
with FGFR2 gene fusions/translocations. Subjects will be randomized 2:1 to receive
infigratinib or gemcitabine plus cisplatin.

Broad Health Conditioncholangiocarcinoma
unresectable cholangiocarcinoma
metastatic cholangiocarcinoma
fibroblast growth factor receptor inhibitor
FGFR2
FGFR2 gene fusions/translocations
BGJ398

Specific Health ConditionCancer
Advanced Cholangiocarcinoma
FGFR2 Gene Mutation

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,SA,VIC,WA,

Hospital
Chris O'Brien Lifehouse Hospital

Hospital
Blacktown Hospital

Hospital
Royal Adelaide Hospital

Hospital
St John of God Hospital Subiaco

Phase of TrialPhase 3

Key inclusion criteria

Inclusion Criteria:

    -  Histologically or cytologically confirmed unresectable locally advanced or metastatic
       cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma
       are not eligible

    -  Documented FGFR2 gene fusions/translocations

    -  Have an archival tissue sample available with sufficient tumor for central FGFR2
       fusion/translocation molecular testing. However, if an archival tissue sample is not
       available, a newly obtained (before randomization) tumor biopsy may be submitted
       instead.

    -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

    -  Able to swallow and retain oral medication

    -  Willingness to avoid pregnancy or father children

  Exclusion Criteria:

    -  Received treatment with any systemic anti-cancer therapy for unresectable locally
       advanced or metastatic cholangiocarcinoma. Prior neoadjuvant or adjuvant therapy is
       permitted if completed > 6 months after the last dose of neoadjuvant or adjuvant
       therapy.

    -  History of a liver transplant

    -  Received previously or currently is receiving treatment with a mitogen activated
       protein kinase kinase (MEK) or selective FGFR inhibitor

    -  Have impairment of gastrointestinal (GI) function or GI disease that may significantly
       alter the absorption of oral infigratinib (such as, ulcerative diseases, uncontrolled
       nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).

    -  Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g.,
       parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis
       etc.

    -  History and/or current evidence of extensive tissue calcification including, but not
       limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung
       with the exception of calcified lymph nodes, minor pulmonary parenchymal
       calcifications, and asymptomatic coronary calcification

    -  Current evidence of corneal or retinal disorder/keratopathy

    -  Receiving and continued treatment or are planning to receive agents or consuming foods
       that are known strong inducers or inhibitors of CYP3A4 and medications which increase
       serum phosphorus and/or calcium concentration

    -  Clinically significant or uncontrolled cardiac disease

    -  Recent (= 3 months prior to first dose of study drug) transient ischemic attack or
       stroke

    -  Severe hearing loss

    -  Severe neuropathy

    -  History of another primary malignancy within 3 years except adequately treated in-situ
       carcinoma of the cervix or non-melanoma skin cancer or other curatively treated
       malignancy that is not expected to require treatment

    -  Pregnant or breastfeeding

    -  Have known microsatellite instability-high (MSI-H) disease and the decision is made by
       the treating investigator that an alternative, non-study therapy is warranted
       according to standard of care.

    -  Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents,
       infigratinib, or their excipients

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

This is an open-label, multicenter, global Phase 2 basket study of entrectinib (RXDX-101) for
the treatment of patients with solid tumors that harbor an NTRK1/2/3, ROS1, or ALK gene
fusion. Patients will be assigned to different baskets according to tumor type and gene
fusion.

Broad Health ConditionEntrectinib
RXDX-101
TrkA
TrkB
TrkC
NTRK1
NTRK2
NTRK3
ROS1
ALK
Trk Fusions
NTRK Gene Rearrangements
ROS1 Fusions
ROS1 Gene Rearrangements
ALK Fusions
ALK Gene Rearrangements
Basket study
Non-small cell lung cancer
Colorectal cancer
Salivary gland cancers
Primary brain tumors
Melanoma
Sarcomas
Papillary thyroid cancer
Renal cell cancer
Pancreatic cancer
Breast cancer
Cholangiocarcinoma
Head & Neck cancers
Ovarian cancer
Neuroendocrine tumors
Anaplastic Large Cell Lymphoma

Specific Health ConditionCancer
Breast Cancer
Cholangiocarcinoma
Colorectal Cancer
Head and Neck Neoplasms
Lymphoma, Large-Cell, Anaplastic
Melanoma
Neuroendocrine Tumors
Non-Small Cell Lung Cancer
Ovarian Cancer
Pancreatic Cancer
Papillary Thyroid Cancer
Primary Brain Tumors
Renal Cell Carcinoma
Sarcomas
Salivary Gland Cancers
Adult Solid Tumor

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,SA,VIC,

Hospital
Liverpool Hospital

Hospital
Newcastle Private Hospital

Hospital
Austin Hospital

Phase of TrialPhase 2

Key inclusion criteria

Inclusion Criteria:

    -  Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic
       solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement

       - Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene
       rearrangement of interest may be eligible provided they meet all other
       inclusion/exclusion criteria

    -  For patients enrolled via local molecular testing, an archival or fresh tumor tissue
       (unless medically contraindicated) is required to be submitted for independent central
       molecular testing at Ignyta's CLIA laboratory post-enrollment

    -  Measurable or evaluable disease

    -  Patients with CNS involvement, including leptomeningeal carcinomatosis, which is
       either asymptomatic or previously-treated and controlled, are allowed

    -  Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1,
       or ALK inhibitors in patients who have tumors that harbor those respective gene
       rearrangements)

       - Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged
       NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are
       prohibited.

    -  At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior
       chemotherapy or small molecule targeted therapy

    -  At least 4 weeks must have elapsed since completion of antibody-directed therapy

    -  Prior radiotherapy is allowed if more than 14 days have elapsed since the end of
       treatment

    -  Eastern Cooperative Oncology Group (ECOG) performance status = 2 and minimum life
       expectancy of 4 weeks

    -  Adequate organ function as defined per protocol

    -  Ability to swallow entrectinib intact

    -  Other protocol specified criteria

  Exclusion Criteria:

    -  Current participation in another therapeutic clinical trial

    -  Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in
       patients who have tumors that harbor those respective gene rearrangements

       - Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged
       NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are
       prohibited.

    -  History of other previous cancer that would interfere with the determination of safety
       or efficacy

    -  Incomplete recovery from any surgery

    -  History of recent (within the past 3 months) symptomatic congestive heart failure or
       ejection fraction =50% observed during screening for the study

    -  History of non-pharmacologically induced prolonged QTc interval

    -  History of additional risk factors for torsades de pointes

    -  Peripheral neuropathy Grade = 2

    -  Known active infections

    -  Active gastrointestinal disease or other malabsorption syndromes

    -  Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase
       inhibitor-induced pneumonitis

    -  Other protocol specified criteria

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

This is a multicentre, two stage, prospective, randomized, controlled phase III trial
designed to assess the clinical performance of gemcitabine with cisplatin and observation vs.
standard of care (capecitabine) and observation in patients after curative intent resection
of cholangiocarcinoma and muscle invasive gall bladder carcinoma.

Broad Health Conditionadjuvant chemotherapy
cholangiocarcinoma
muscle invasive gall bladder carcinoma
translational research
multidisciplinary
AIO, DGAV, DGVS

Specific Health ConditionCancer
Cholangiocarcinoma
Gall Bladder Carcinoma

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,QLD,SA,WA,

Hospital
Bankstown Hospital

Hospital
Nepean Hospital Cancer Care

Hospital
St. George Hospital

Hospital
Prince of Wales Hospital

Hospital
Townsville Hospital

Hospital
Royal Brisbane and Women's Hospital

Hospital
Princess Alexandra Hospital

Hospital
Fiona Stanley Hospital Perth

Hospital
Sir Charles Gairdner Hospital

Phase of TrialPhase 3

Key inclusion criteria

All enrolled patients will postoperatively be assessed for eligibility for the treatment
  phase. Additionally patients not previously enrolled into the trial for whatever reason
  (e.g. incidental finding during surgery) will be evaluated for eligibility.

    -  Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or
       extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after
       radical surgical therapy with macroscopically complete resection (mixed tumor entities
       (HCC/CCA) are excluded)

    -  Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start
       of chemotherapy

    -  ECOG 0-1

    -  Age =18 years

    -  Adequate hematologic function

    -  Adequate liver function

    -  Adequate renal function

    -  No active uncontrolled infection, except chronic viral hepatitis under antiviral
       therapy

    -  No concurrent treatment with other experimental drugs or other anti-cancer therapy,
       treatment in a clinical trial within 30 days prior to randomization

    -  Negative serum pregnancy test within 7 days of starting study treatment in
       pre-menopausal women and women <1 year after the onset of menopause (Note: a negative
       test has to be reconfirmed by a urine test, should the 7-day window be exceeded)

  Criteria for initial study enrolment

    -  Written informed consent

    -  No prior chemotherapy for cholangiocarcinoma

    -  No previous malignancy within 3 years or concomitant malignancy, except:
       non-melanomatous skin cancer or adequately treated in situ cervical cancer

    -  No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
       IV, unstable angina pectoris, history of myocardial infarction in the last 3 months,
       significant arrhythmia)

    -  Absence of psychiatric disorder precluding understanding of information of trial
       related topics and giving informed consent

    -  No serious underlying medical conditions (judged by the investigator), that could
       impair the ability of the patient to participate in the trial

    -  Fertile women (< 1 year after last menstruation) and procreative men willing and able
       to use effective means of contraception (oral contraceptives, intrauterine
       contraceptive device, barrier method of contraception in conjunction with spermicidal
       jelly or surgically sterile)

    -  No pregnancy or lactation

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No