Clinical Trial Details

Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer

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Trial Information

Broad Health Condition Biliary Tract Cancer

Specific Health Condition

Trial FocusTreatment

Recruitment statusRecruiting

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

Hospital
St George Hospital
Newcastle Private Hospital
Westmead Hospital
The Alfred Hospital
Fiona Stanley Hospital
Sir Charles Gairdner Hospital

Phase of TrialPhase 3

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
Eligibility

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 (AJCC edition 8, 2018). 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 =9 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 activated partial thromboplastin
            time (aPTT) <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 any
       parenteral excipients (e.g. dimethylacetamide [DMA], Cremophor EL, Polysorbate 80,
       Solutol HS 15).

    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, surgically excised or potentially
       curatively treated ductal carcinoma in situ of the breast, or low grade prostate
       cancer or patients after prostatectomy not requiring treatment. Patients with previous
       invasive cancers are eligible if treatment was completed more than 3 years prior to
       initiating the current study treatment, and the patient has had no evidence of
       recurrence since then.

    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

Contact details and further information

Sponsor Primary Sponsor Type: Other
Primary Sponsor Name: NuCana plc

Trial websitehttps://clinicaltrials.gov/show/NCT04163900

Trial IDNCT04163900