Study of CX-4945 in Combination with Gemcitabine and Cisplatin for Frontline Treatment of Cholangiocarcinoma

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    I/II What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 14-000308
    • Jacksonville, Florida: 14-000308
    • Rochester, Minnesota: 14-000308
  • NCT ID:

    NCT02128282
  • Sponsor Protocol Number:

    S4-13-001

About this study

This study considers the safety and tolerability of increasing doses of CX-4945 in combination with gemcitabine plus cisplatin to determine the maximum tolerated dose (MTD), followed by a randomized study that compares antitumor activity in cholangiocarcinoma patients receiving the standard of care gemcitabine plus cisplatin versus CX-4945 at the combination MTD with gemcitabine plus cisplatin.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Presence of an unresectable liver mass consistent with cholangiocarcinoma, for which treatment with gemcitabine plus cisplatin is intended.
  • For patients enrolled in the Dose Escalation Phase, one or more tumors measurable on radiograph or CT scan, or evaluable disease defined as non-measurable lesions per RECIST v. 1.1 (e.g., malignant ascites). All patients enrolled to the Randomized Study Phase must have measurable disease only.
  • Laboratory data as specified below:
    • Hematology: Absolute neutrophil count (ANC) >1,500 cells/mm3, platelet count >100,000 cells/ mm.cu. and hemoglobin > 9 g/dL
    • Hepatic: bilirubin <1.5 X Upper Limit of Normal (ULN); alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN
    • Renal: serum creatinine within normal limits (WNL), defined as within 25% of the institution's stated reference range, or a calculated creatinine clearance >45 mL/min/1.73 m. sq. for patients with abnormal, increased, creatinine levels.
    • Coagulation: International Normalized Ratio (INR) < 1.5 times normal, activated Partial Thromboplastin Time (aPTT) < 1.5 times normal. Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible for the trial if INR and aPTT are within the acceptable therapeutic limits for the institution.
  • Estimated life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1.

Exclusion Criteria:

  • A history of prior systemic treatment with gemcitabine or cisplatin. At least six months must have elapsed if gemcitabine or cisplatin was administered in an adjuvant treatment setting.
  • Seizure disorders requiring anticonvulsant therapy.
  • Known brain metastases (unless previously treated and well controlled for a period of at least 3 months).
  • Major surgery other than diagnostic surgery, within 4 weeks prior to the first dose of test drug, minor surgery including diagnostic surgery within 2 weeks (14 days) excluding central IV port placements and needle aspirate/core biopsies. Radio frequency ablation or transcatheter arterial chemoembolization within 6 weeks prior to the first dose of test drug.
  • Treatment with radiation therapy or surgery within one month prior to study entry.
  • Treatment with chemotherapy or investigational drugs within 21 days prior to the screening visit. Acute toxicities from prior therapy must have resolved to Grade ≤ 1 above baseline.
  • Patients with a history of another malignancy within 3 years of the baseline visit. (Patients with cutaneous carcinomas or in-situ carcinomas will be considered for study entry on a case-by-case basis).
  • Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure).
  • Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis.
  • Difficulty with swallowing or an active malabsorption syndrome.
  • Chronic diarrhea (excess of 2-3 stools/day above normal frequency).
  • Gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
  • History of gastric or small bowel surgery involving any extent of gastric or small bowel resection.
  • Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis.
  • Patients who have exhibited allergic reactions to a similar structural compound or to a formulation component of CX-4945.
  • Concomitant use either of warfarin and/or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins).

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Contact us for the latest status

Cancer Center Clinical Trials Referral Office

855-776-0015