A Study to See the Effects That a New Combination of the Three Drugs, Nab-paclitaxel, Gemcitabine, and Cisplatin Has on Biliary Tract Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02632305
Recruitment Status : Recruiting
First Posted : December 16, 2015
Last Update Posted : March 14, 2018
Information provided by (Responsible Party):
AHS Cancer Control Alberta

Brief Summary:

You are being asked to take part in this study because you have a biliary cancer that is incurable and has spread to other organs. Chemotherapy is often used to help shrink the cancer temporarily and may improve survival. In Canada, the combination of gemcitabine and cisplatin is the chemotherapy combination used to treat biliary cancer that has spread. There is no other known treatment for biliary cancer that has spread to other organs. It is hoped that this new combination of drugs (nab-paclitaxel, gemcitabine, and cisplatin) will improve the tumor shrinkage rate.

This study is being done because we do not know whether 2 or 3 chemotherapy drugs is better to treat biliary cancers.

We hope to learn whether giving nab-paclitaxel, gemcitabine, and cisplatin together in patients with biliary cancer can increase tumor shrinkage without too many side effects.

The purpose of this study is to find out what effects (good and bad) nab-paclitaxel, gemcitabine, and cisplatin has on you and your biliary cancer.

Condition or disease Intervention/treatment Phase
Unresectable Biliary Tract Cancer Drug: nab-paclitaxel in combination with gemcitabine + cisplatin Phase 2

Detailed Description:

There is increasing evidence that there is a large degree of pathologic homology between the pancreas and biliary tract. Indeed, the biliary tract has been referred to as "an incomplete pancreas" and embryologically the two originate from the same structure. It is thus plausible that oncogenesis in the pancreas and biliary tract are related and that pancreas and biliary cancers have reciprocal effective treatment strategies.

To date, the only chemotherapeutic agents effective in advanced biliary tract tumors is the combination of gemcitabine and cisplatin. Known and approved therapies for advanced pancreas cancer include single agent gemcitabine, the four drug combination of FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan), the questionable limited benefit of inhibiting the epidermal growth factor receptor pathway, and most recently the combination of gemcitabine and nab-paclitaxel.

Based on promising results in pancreas cancer, investigators hypothesize nab-paclitaxel in combination with gemcitabine + cisplatin will be an effective cytotoxic combination in BTC treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentre, Open-label Phase II Study of Nab-paclitaxel in Combination With Gemcitabine + Cisplatin as First Line Treatment in Patients With Unresectable Biliary Tract Cancer
Actual Study Start Date : July 13, 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : June 2020

Arm Intervention/treatment
Experimental: Treatment

Eligible patients will receive nab-paclitaxel in combination with gemcitabine + cisplatin at the recommended phase II dose based on the phase I study completed in metastatic pancreas cancer patients.

The doses of study drugs will be as follows:

  • nab-Paclitaxel 100 mg/m2 day 1 and 8 every 21 days
  • Cisplatin 25 mg/m2 day 1 and 8 every 21 days
  • Gemcitabine 800 mg/m2 day 1 and 8 every 21 days

Nab-paclitaxel will be administered first followed by cisplatin and then gemcitabine on day 1 and 8 of each treatment cycle. Cycles will be 3 weeks in length (21 days).

Drug: nab-paclitaxel in combination with gemcitabine + cisplatin
Patients with unresectable BTC will be treated with the triple combination of nab-paclitaxel in combination with gemcitabine + cisplatin

Primary Outcome Measures :
  1. Overall response rates [ Time Frame: 1 year ]
    defined as the sum of complete response rates and partial response rates, of nab-paclitaxel in combination with gemcitabine + cisplatin in first line treatment of unresectable biliary tract cancer (BTC).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically documented locally advanced or metastatic BTC (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma) not previously treated with palliative systemic therapy or radiation
  2. Unresectable disease based on the presence of clinically and/or radiologically documented measurable disease based on RECIST 1.1. Patients must have measurable disease; evaluable only disease will not be permitted.
  3. ECOG performance status of 0 - 1.
  4. Age ≥ 18 years.
  5. Life expectancy of at least 3 months based on discretion of treating oncologist.
  6. Adequate hematologic function defined by the following laboratory parameters:

    • Hemoglobin ≥ 9 g/dL
    • Platelet count ≥ 100 x 109/L
    • Absolute granulocyte count ≥ 1.5 x 109/L
  7. Adequate hepatic and renal function defined by the following laboratory parameters:

    • AST and ALT and alkaline phosphatase ≤ 2.5 X upper limit of institutional normal (≤ 5 if liver metastases)
    • bilirubin ≤ 1.5 X upper limit of institutional normal
    • serum creatinine ≤ upper limit of institutional normal OR calculated creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault formula
  8. Patients may have received prior surgery if this surgery was ≥ 4 weeks before study entry and patients must have recovered from the toxic effects of this treatment.
  9. Prothrombin time- international normalized ratio (PT-INR) and partial thromboplastin time (PTT) must be within +/- 15% normal range.
  10. Patients who have treated brain metastasis (via local radiation standards or surgical resection or local ablative techniques) and who are either off steroids or on a stable dose of steroids for at least one month (30 days), AND who are off anticonvulsants, AND have radiological documented stability of lesions for at least 3 months may be eligible. Each case should be discussed with the study Chair.
  11. Patients must have the ability to read, understand, and sign an informed consent and must be willing to comply with study treatment and follow-up.
  12. Female subjects of childbearing potential, defined as a sexually mature woman who 1) has not undergone hysterectomy or bilateral oophorectomy OR 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time during the preceding 24 consecutive months) must:

    • either commit to true abstinence or agree to the use of a 2 physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive with spermicide; or vasectomized partner) while on clinical trial and for at least 3 months following the last does of study medication; and
    • has a negative serum pregnancy test (β-hCG) result at screening. Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for 6 months following study medication discontinuation, even if he has undergone a success vasectomy.

Exclusion Criteria:

  1. Patients who have received prior palliative chemotherapy for their advanced BTC.
  2. Prior curative or palliative radiation treatment to the pelvis or radiation therapy to ≥ 25% of bone marrow stores.
  3. History of bowel obstruction due to peritoneal metastases or clinically documented ascites requiring paracenteses.
  4. Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix or uterus or non-melanoma skin cancer or in-situ carcinoma of the prostate (Gleason score ≤ 7, with all treatment being completed 6 months prior to enrollment, unless at least 5 years have elapsed since last treatment and the patient is considered cured).
  5. Active bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
  6. Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the investigator, increase the risk of serious neutropenic complications.
  7. Any serious medical condition within 6 months prior to study entry such as myocardial infarction, uncontrolled congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, cerebrovascular diseases, uncontrolled hypertension, uncontrolled diabetes, uncontrolled psychiatric disorder, serious infection, active peptic ulcer disease, or other medical condition that may be aggravated by treatment.
  8. Pre-existing neuropathy ≥ grade 1 from any cause.
  9. Patients with unstable metastasis to the central nervous system (CNS). A CT scan or MRI is NOT required to rule out brain metastases unless there is clinical suspicion of CNS involvement.
  10. Pregnant or lactating women; women of child bearing potential must have a negative serum pregnancy test within 7 days of trial registration. Women or men of child bearing potential must use effective contraception (defined by the treating physician) which must be documented in study CRFs.
  11. History of allergic reaction to planned study medications.
  12. Patient has a ≥ 20% decrease in serum albumin level between baseline visit, if available, and within 72 hours prior to first study treatment dose.
  13. Patient is on coumadin.
  14. History of interstitial lung disease.
  15. History of connective tissue disorders (e.g. lupus, scleroderma, polyarteritis nodosa).
  16. Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures.
  17. Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in the study, places the subject at unacceptable risk if he/she were to participate in the study, or any condition that confounds the ability to interpret data from the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02632305

Contact: Jennifer Spratlin, MD FRCPC 780-432-8513
Contact: Michael Sawyer, MD FRCPC 780-432-8248

Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada
Contact: Jennifer Spratlin, MD FRCPC   
Sponsors and Collaborators
AHS Cancer Control Alberta
Principal Investigator: Jennifer Spratlin, MD FRCPC Alberta Health Services

Responsible Party: AHS Cancer Control Alberta Identifier: NCT02632305     History of Changes
Other Study ID Numbers: AX-CSARC-PI-0001
First Posted: December 16, 2015    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by AHS Cancer Control Alberta:
unresectable biliary tract cancer

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs