Bortezomib With or Without Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer

Stage IV Pancreatic Cancer Clinical Trial

Official title:

A Randomized Phase II Trial of PS-341 and Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00052689
• Other study ID #: NCI-2012-01799
• Secondary ID: NCI-2012-01799NC
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2003
• Last updated: October 7, 2013
• Start date: December 2002

Study information

• Verified date: October 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Randomized phase II trial to compare the effectiveness of bortezomib with or without gemcitabine in treating patients who have metastatic pancreatic cancer. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with gemcitabine may kill more tumor cells.

Description:

OBJECTIVES:

I. Compare the objective response rate in previously untreated patients with metastatic pancreatic adenocarcinoma treated with bortezomib with or without gemcitabine.

II. Compare the toxicity of these regimens in these patients. III. Compare the progression-free, 6-month, and overall survival of patients treated with these regimens.

IV. Compare the change in overall quality of life (QOL) and in subcomponents of QOL of patients after treatment with 2 consecutive courses of these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1of 2 treatment arms.

ARM I: Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Patients with progressive disease crossover to arm II.

ARM II: Patients receive bortezomib as in arm I and gemcitabine IV over 30 minutes on days 1 and 8.

Courses in both arms repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life (QOL) is assessed at baseline and before courses 2 and 4. Patients who crossover to arm II from arm I complete QOL questionnaires before the first 2 courses of arm II therapy.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed metastatic ductal or undifferentiated adenocarcinoma consistent with a pancreatic primary for which no standard curative measures exist

• No locally advanced disease only

• No islet cell, acinar cell, or cystadenocarcinomas

• Measurable disease

• At least one lesion whose longest diameter can be accurately measured as 2 cm or greater by conventional techniques OR 1 cm or greater by spiral CT scan

• A tumor lesion in a previously irradiated area allowed provided it is histologically confirmed disease with radiographic progression from a post-radiotherapy CT scan

• No CNS metastasis

• Performance status - ECOG 0-2

• At least 3 months

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 9.0 g/dL

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (stents allowed)

• AST no greater than 5 times ULN

• PT and PTT no greater than ULN*

• Creatinine no greater than 1.5 times ULN

• No other prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

• No neuropathy greater than grade 1

• No underlying disease state associated with active bleeding

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 6 months after study participation

• More than 4 weeks since prior biologic therapy or immunotherapy

• No concurrent immunotherapy

• No concurrent colony-stimulating factors during the first course of the study

• No prior gemcitabine (even as a radiosensitizing agent)

• No prior chemotherapy

• Radiosensitizing agent as adjuvant therapy or for locally advanced disease allowed

• No other concurrent chemotherapy

• See Disease Characteristics

• More than 4 weeks since prior radiotherapy

• No prior radiotherapy to 25% or more of the bone marrow

• No concurrent radiotherapy

• No prior bortezomib

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Duct Cell Adenocarcinoma of the Pancreas
• Pancreatic Neoplasms
• Stage IV Pancreatic Cancer

Intervention

Drug:
• bortezomib
Given IV
• gemcitabine hydrochloride
Given IV

Locations

Country	Name	City	State
United States	North Central Cancer Treatment Group	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed tumor response (CR, PR) rate in 2 consecutive courses within 6 months (Arm I)	An evaluable patient will be classified as a treatment 'success' if they have a confirmed tumor response (CR, PR). The proportion of successes will be estimated by the total number of evaluable patients. 95% confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.	Up to 6 months	No
Primary	Proportion of patients alive at 6 months (Arm II)	An evaluable patient will be classified a treatment 'success' if they are alive at 6 months. The proportion of successes will be estimated by the total number of evaluable patients. 95% confidence intervals for the true proportion will be calculated according to the approach of Duffy and Santner.	At 6 months	No
Secondary	Survival time	The distribution of survival time will be estimated using the method of Kaplan-Meier.	Time from randomization to death due to any cause, assessed up to 5 years	No
Secondary	Time to disease progression	The distribution of time to progression will be estimated using the method of Kaplan-Meier.	Time from randomization to documentation of disease progression, assessed up to 5 years	No
Secondary	Time to treatment failure		Time from the date of randomization to the date at which the patient is removed from the treatment due to progression, toxicity, or refusal, assessed up to 5 years	No