Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer

August 9, 2013 updated by: Washington University School of Medicine

A Phase II Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer

To determine the activity of gemcitabine combined with carboplatin in the treatment of patients with metastatic or recurrent cholangiocarcinoma or gallbladder cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Due to better non-hematologic toxicity profile, less need for pre- and post chemotherapy hydration, and tolerability as compared to cisplatin, we propose to combine gemcitabine with carboplatin in the treatment of patients with cholangiocarcinoma and gallbladder carcinoma. In lung cancer, available literature suggests that carboplatin is as efficacious as cisplatin.

Several Phase I, II and III studies using gemcitabine with carboplatin have already been done or are currently ongoing. Phase I studies determined the maximum tolerated doses (MTD) of gemcitabine at 800-1250 mg/m2 days 1 and 8 combined with at AUC of 4-5.5, day 1 of a 21-day cycle.

Initial Phase II studies using a 28-day schedule using gemcitabine on days 1,8 and 15 with carboplatin caused severe thrombocytopenia on day 15 precluding day 15 treatment in over 50% of courses. A Spanish Lung Cancer Group conducted a sequential Phase II trial wherein 52% and 30% of the first 33 patients with lung cancer treated using the 28-day schedule were noted to have Grade 4 thrombocytopenia and neutropenia, respectively. Subsequently, the next 56 patients were treated on the 21-day schedule, and despite a higher dose intensity, response rates were equal (45-48%) with less Grade 4 thrombocytopenia (21%) but similar rates of Grade 4 neutropenia (27%).

A randomized Italian Phase II studies have demonstrated that when gemcitabine was given at doses of 1 g/m2 with carboplatin at AUC of 5 mg/mL/min were tolerable and when compared to gemcitabine and cisplatin caused less non-hematologic toxicities. Current Phase III trials in lung cancer utilizes the 21-day schedule with gemcitabine at 1000 mg/m2 on days 1 and 8 and carboplatin at AUC of 5.5.

Therefore, our proposed schedule will be gemcitabine at 1000 mg/m2 IV over 30 minutes on days 1 and 8 with carboplatin dosed at an AUC of 5 on day 1 of a 21-day cycle.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  1. Patients must have biopsy-proven locally-advanced, metastatic or recurrent adenocarcinoma of the biliary ducts or gallbladder.
  2. Patients must have measurable disease.
  3. Patients must be 18 years or older.
  4. Patients must have a NCI CTC Performance Status of 0-2.
  5. Patients must have a life expectancy of >= 3 months.
  6. Patients must not have any prior chemotherapy for metastatic disease. Prior adjuvant radiation therapy and chemotherapy with 5FU and/or gemcitabine is allowed.
  7. At least 3 weeks should have elapsed since any surgery requiring general anesthesia.
  8. Patients must have no prior malignancies except for basal or squamous skin cancers, cervical carcinoma-in-situ.
  9. Pregnant patients are not eligible. Non-pregnant status will be determined in all women of childbearing potential. All patients will be required to use an effective means of contraception if sexually active during therapy.

  10. Initial Required Laboratory Values:

    • 1. Absolute neutrophil count >= 1,500/mm3, platelet count >= 100,000/mm3, and hemoglobin >= 9 g/dL.
    • 2. Serum creatinine should be <= 2 mg/dL.
    • 3. Serum bilirubin should be <= 3.0 mg/dL (biliary stents allowed).
    • 4. Serum transaminases should be <= 5-fold the institutional upper limits.
  11. Patients must not have any co-existing severe medical illnesses, such as unstable angina, uncontrolled diabetes mellitus, uncontrolled arrhythmia or uncontrolled infection.
  12. Patients must be able to sign an informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gemcitabine + Carboplatin

Gemcitabine 1000 mg/m2 IV for 30 minutes on days 1 and 8 of 21 day cycle. Maximum of 9 cycles.

Carboplatin AUC 5 IV for 1 hour on day 1 of 21 day cycle. Maximum of 9 cycles.
Drug: Gemcitabine
Other Names:
  • Gemzar
Drug: Carboplatin
Other Names:
  • Paraplatin
  • Paraplatin-AQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine the response rate and time to failure for patients treated with this regimen
Time Frame: Every 3 cycles for a maximum of 9 cycles
1 cycle = 21 days
Every 3 cycles for a maximum of 9 cycles

Secondary Outcome Measures

Outcome Measure
Time Frame
To describe the toxicities associated with gemcitabine and carboplatin in patients with cholangiocarcinoma or gallbladder cancer.
Time Frame: 30 days after last dose of study drug
30 days after last dose of study drug
To assess the clinical benefit, or lack thereof, of chemotherapy on patient's performance status and weight.
Time Frame: At the end of study treatment
At the end of study treatment
Time to progression
Time Frame: Every 3 months until progression
Every 3 months until progression
Survival times
Time Frame: Every 3 months until patient death
Every 3 months until patient death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2002

Primary Completion (Actual)

January 1, 2007

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

April 11, 2008

First Submitted That Met QC Criteria

April 16, 2008

First Posted (Estimate)

April 17, 2008

Study Record Updates

Last Update Posted (Estimate)

August 13, 2013

Last Update Submitted That Met QC Criteria

August 9, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01-0925

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe