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

Cholangiocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00660140
• Other study ID #: 01-0925
• Status: Completed
• Phase: Phase 2
• First received: April 11, 2008
• Last updated: August 9, 2013
• Start date: March 2002
• Est. completion date: April 2009

Study information

• Verified date: August 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 2009
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Gallbladder Cancer
• Gallbladder Neoplasms

Intervention

Drug:
• Gemcitabine

• Carboplatin

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the response rate and time to failure for patients treated with this regimen	1 cycle = 21 days	Every 3 cycles for a maximum of 9 cycles	No
Secondary	To describe the toxicities associated with gemcitabine and carboplatin in patients with cholangiocarcinoma or gallbladder cancer.		30 days after last dose of study drug	Yes
Secondary	To assess the clinical benefit, or lack thereof, of chemotherapy on patient's performance status and weight.		At the end of study treatment	No
Secondary	Time to progression		Every 3 months until progression	No
Secondary	Survival times		Every 3 months until patient death	No

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine