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

The purpose of this study is to determine the safety and efficacy of combination therapy with
pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative
breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma
(GBM), or biliary tract cancers (BTC). Participants will be enrolled into initial
tumor-specific cohorts which will be expanded if adequate efficacy is determined.

Broad Health Conditionprogrammed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
programmed cell death ligand 2 (PD-L2, PDL2)
tyrosine kinase inhibitor (TKI)
multiple TKI
Vascular Endothelial Growth Factor Receptor (VEFG)
Fibroblast Growth Factor (FGF)
Platelet-Derived Growth Factor (PDGF)

Specific Health ConditionCancer
Advanced Solid Tumors
Triple Negative Breast Cancer
Ovarian Cancer
Gastric Cancer
Colorectal Cancer
Glioblastoma
Biliary Tract Cancers

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
QLD,VIC,

Hospital
Royal Brisbane and Women s Hospital ( Site 0901)

Phase of TrialPhase 2

Key inclusion criteria

Inclusion Criteria:

    -  Has a histologically or cytologically-documented, advanced (metastatic and/or
       unresectable) solid tumor that is incurable and for which prior standard systemic
       therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric
       Cancer, Colorectal Cancer: non-microsatellite instability-High/proficient mismatch
       repair (MSI-H/pMMR) tumor, GBM, BTC: intrahepatic, extrahepatic cholangiocarcinoma and
       gall bladder cancer; excludes Ampulla of Vater

    -  Must have progressed on or since the last treatment

    -  Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the
       local site investigator/radiology and confirmed by BICR

    -  Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or
       excisional biopsy of a tumor lesion not previously irradiated

    -  Male participants agree to use approved contraception during the treatment period for
       at least 30 days after the last dose of lenvatinib, or refrain from heterosexual
       intercourse during this period

    -  Female participants are not pregnant or breastfeeding, and are not a woman of
       childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during
       the treatment period (or 14 days prior to the initiation of study treatment for oral
       contraception) and for at least 120 days post pembrolizumab, or 30 days post
       lenvatinib, whichever occurs last

    -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7
       days of study treatment initiation

    -  Has adequate organ function

  For Triple Negative Breast Cancer Participants:

    -  Has received one or 2 prior lines of therapy

    -  Has Lactate Dehydrogenase (LDH) <2.0 x Upper Limit of Normal (ULN)

    -  Has locally determined results for estrogen receptor, progesterone receptor, and human
       epidermal growth factor receptor 2 tumor analyses

  For Ovarian Cancer Participants:

  - Has received 3 prior lines of therapy

  For Gastric Cancer Participants:

  - Has received 2 prior lines of therapy

  For Colorectal Cancer Participants:

    -  Has received 2 prior lines of therapy

    -  Has a locally determined non-MSI-H/pMMR tumor

  For GBM Participants:

    -  Has failed initial systemic therapy for newly diagnosed GBM

    -  Have the following time periods elapsed before the projected start of scheduled study
       treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from
       stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at
       least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent,
       5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at
       least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies
       and 1 week for cancer vaccines

    -  Be neurologically stable (e.g. without a progression of neurologic symptoms or
       requiring escalating doses of systemic steroid therapy within last 2 weeks) and
       clinically stable

    -  Has histologically confirmed World Health Organization (WHO) Grade IV GBM

  For Biliary Tract Cancer Participants:

    -  Has received 1 prior line of therapy

    -  Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6

  Exclusion Criteria:

    -  Has presence of gastrointestinal condition including malabsorption that might affect
       the absorption of lenvatinib

    -  Has radiographic evidence of major blood vessel invasion/infiltration

    -  Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the
       first dose of study treatment

    -  Has significant cardiovascular impairment within 12 months of the first dose of study
       treatment: such as history of congestive heart failure greater than New York Heart
       Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular
       accident (CVA), or cardiac arrhythmia associated with hemodynamic instability

    -  Has a history of arterial thromboembolism within 12 months of start of study treatment

    -  Has a known additional malignancy that is progressing or has required active treatment
       within the past 3 years

    -  Has had major surgery within 3 weeks prior to first dose of study interventions

    -  Serious nonhealing wound, ulcer or bone fracture

    -  Has biologic response modifiers (e.g. granulocyte colony-stimulating factor) within 4
       weeks before study entry

    -  Has preexisting =Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula

    -  Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2
       agent or with an agent directed to another stimulatory or co-inhibitory T-cell
       receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis
       factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor
       superfamily member 9 [CD137])

    -  Has received prior systemic anti-cancer therapy including investigational agents
       within 4 weeks or 5 times the half-life time, whichever is shorter prior to study
       treatment start

    -  If participant received major surgery, they must have recovered adequately from the
       toxicity and/or complications from the intervention prior to starting study treatment

    -  Has received prior radiotherapy within 2 weeks of start of study treatment.
       Participants must have recovered from all radiation-related toxicities, not require
       corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
       for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system
       (CNS) disease

    -  Has received a live vaccine within 30 days prior to the first dose of study treatment

    -  Has known intolerance to lenvatinib (and/or any of the excipients)

    -  Is currently participating in or has participated in a study of an investigational
       agent or has used an investigational device within 4 weeks prior to the first dose of
       study treatment

    -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
       (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
       immunosuppressive therapy within 7 days prior the first dose of study treatment

    -  Has known active CNS metastases and/or carcinomatous meningitis

    -  Has tumors involving the brain stem

    -  Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

    -  Has an active autoimmune disease that has required systemic treatment in past 2 years

    -  Has a history of (non-infectious) pneumonitis that required steroids or has current
       pneumonitis

    -  Has an active infection requiring systemic therapy

    -  Has a known history of human immunodeficiency virus (HIV) infection

    -  Has a known history of hepatitis B or known active hepatitis C virus infection

    -  Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

    -  Is pregnant or breastfeeding or expecting to conceive or father children within the
       projected duration of the study, starting with the screening visit through 120 days
       after the last dose of study treatment

    -  Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell
       transplant requiring chronic immunosuppressant therapy necessary to prevent graft
       rejection)

  For Colorectal Cancer Participants:

  - Has MSI-H/dMMR disease

  For GBM Participants:

    -  Has carcinomatous meningitis

    -  Has recurrent tumor greater than 6 cm in maximum diameter

    -  Has tumor primarily localized to the brainstem or spinal cord

    -  Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease

    -  Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance
       imaging (MRI) scan other than those that are grade = 1 and either post-operative or
       stable on at least 2 consecutive MRI scans

    -  Has received Optune® TTFields within 2 weeks of study intervention

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single
agent and in combination with other anti-cancer drugs in patients with advanced solid tumors
and gliomas.

The study is divided into two parts: single agent FT-2102 followed by combination therapy.

Part 1: A single agent, open-label study in up to five cohorts (glioma, hepatobiliary tumors,
chondrosarcoma, intrahepatic cholangiocarcinoma, and other IDH1 mutant solid tumors) that
will include a Phase 1 dose confirmation followed by a Phase 2 investigation of clinical
activity in up to 4 cohorts. During the dose confirmation, additional doses or altered dose
schedules may be explored.

Part 2: An open-label study of FT-2102 in combination with other anti-cancer agents. Patients
will be enrolled across 4 different disease cohorts, examining the effect of FT-2102 +
azacitidine (glioma and chondrosarcoma), FT-2102+nivolumab (hepatobiliary tumors) and
FT-2102+gemcitabine/cisplatin (intrahepatic cholangiocarcinoma). There will be a safety
lead-in followed by a Phase 2 evaluation in up to four cohorts of patients.

Broad Health Condition

Specific Health ConditionCancer
Cohort 1a and 1b: Glioma
Cohort 1a and 1b: Glioblastoma Multiforme
Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas)
Cohort 3a and 3b: Chondrosarcoma
Cohort 4a and 4b: Intrahepatic Cholangiocarcinoma
Cohort 5a: Other Solid Tumors With IDH1 Mutations

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
VIC,

Hospital
Austin Hospital

Phase of TrialPhase 1/Phase 2

Key inclusion criteria

Key Inclusion Criteria:

    -  Patients must have documented IDH1-R132 gene-mutated disease as evaluated by site

    -  Glioma: Advanced glioma that has recurred or progressed following standard therapy, or
       that has not responded to standard therapy.

    -  Hepatobiliary cancer that is relapsed/refractory or intolerant to approved
       standard-of-care therapy (included: hepatocellular carcinoma, bile duct carcinoma,
       intrahepatic cholangiocarcinoma or other hepatobiliary carcinomas)

    -  Chondrosarcoma that is relapsed or refractory and either locally advanced or
       metastatic and not amenable to complete surgical excision

    -  Intrahepatic cholangiocarcinoma that is advanced nonresectable or metastatic
       cholangiocarcinoma not eligible for curative resection or transplantation. Phase
       1b/Safety Lead-in of Phase 2: relapsed or refractory disease. Combination Phase 2
       (beyond Safety Lead-in): have received no more than 1 cycle of gemcitabine/cisplatin
       therapy

    -  Other solid tumors that have relapsed or refractory to standard-of-care therapy with
       no other available therapeutic options

    -  Good performance status

    -  Good kidney and liver function

  Key Exclusion Criteria:

    -  Prior solid organ or hematopoietic cell transplant

    -  Prior treatment with IDH1 inhibitor (Single agent cohorts only)

    -  Congestive heart failure (New York Heart Association Class III or IV) or unstable
       angina pectoris. Previous history of myocardial infarction within 1 year prior to
       study entry, uncontrolled hypertension or uncontrolled arrhythmias

    -  Unstable or severe, uncontrolled medical condition (e.g., unstable cardiac function,
       unstable pulmonary condition including pneumonitis and/or interstitial lung disease,
       uncontrolled diabetes)

    -  Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
       therapy

    -  PD-1 only: active autoimmune disease

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

Trial summary

This is an open-label, nonrandomized, Phase 1 dose-escalation, dose-expansion, and Phase 2
study targeting tumors with FGF/FGFR aberrations. The purpose of the study is to evaluate the
safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of TAS-120 in patients
with advanced solid tumors with and without FGF/FGFR-related abnormalities.

The study will be conducted in 3 parts, (1) Dose escalation to determine the MTD and/ or RP2D
of TAS-120 in which this part of the study has been completed; (2) Phase 1 expansion to
further evaluate the safety and efficacy of RP2D of TAS-120 in patients with tumors harboring
specific FGFR aberrations, specifically in patients with cholangiocarcinoma, gliomas ,
urothelial carcinomas and any other tumors with FGFR fusion or activating mutation or
amplification. Up to approximately 185 patients will be enrolled in the phase 1 expansion;
and (3) Phase 2 study to confirm ORR of TAS-120 in intra-hepatic CCA patients with tumors
harboring FGFR2 gene fusions. Approx. 100 patients will be enrolled in phase 2.

Broad Health ConditionBreast Cancer
Non Small Cell Lung Cancer
Gastric Cancer
FGF
FGFR
FGFR abnormality
TAS-120
Dose Escalation

Specific Health ConditionCancer
Cholangiocarcinoma
Brain Tumor
Urothelial Cancer
Other Tumor Types With FGFR2 Gene Fusions
Activating Mutations
FGFR2 Amplification

Trial FocusTreatment

Recruitment statusRecruiting

Phase of TrialPhase 1/Phase 2

Key inclusion criteria

Inclusion Criteria:

  Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting
  the following criteria:

  Phase 1 Expansion

    1. Patient has failed all standard therapies or standard therapy does not exist or is not
       tolerated.

    2. Patient has specific FGF/FGFR aberrations

         -  Intrahepatic or extrahepatic cholangiocarcinoma with FGFR2 gene fusions or other
            FGFR2 abnormalities, i.e., gene mutations (see Appendix A), rearrangements or
            amplifications

         -  Glioblastoma or grade III glioma (i.e., anaplastic astrocytoma or anaplastic
            oligodendroglioma) with FGFR gene fusions or activating mutations.

         -  Advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations

         -  All other tumor types harboring FGF9, FGF19 or FGFR2 amplifications (= 10
            copies), FGFR gene fusions, or FGFR activating mutations

  Phase 2

    1. Patient has histologically or cytologically confirmed, locally advanced, metastatic,
       unresectable iCCA harboring FGFR2 gene fusions based on results from a NGS assay by
       the Sponsor's designated central laboratory

    2. Patient has been treated with and failed at least one prior systemic gemcitabine and
       platinum-based chemotherapy for the advanced disease

    3. Must have documentation of radiographic progression of disease on prior systemic
       therapy

    4. Patient has measurable disease as defined by Response Evaluation Criteria in Solid
       Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO
       criteria (2010) for brain tumors.

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

    6. Adequate organ function

  Exclusion Criteria:

  A patient will be excluded from this study if any of the following criteria are met:

    1. History and/or current evidence of non-tumor related alteration of calcium-phosphorus
       homeostasis.

    2. History and/or current evidence of clinically significant ectopic
       mineralization/calcification.

    3. History and/or current evidence of clinically significant retinal disorder confirmed
       by retinal examination.

    4. A serious illness or medical condition(s)

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No