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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00052689
First received: January 24, 2003
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Duct Cell Adenocarcinoma of the Pancreas
Stage IV Pancreatic Cancer
Drug: bortezomib
Drug: gemcitabine hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of PS-341 and Gemcitabine in Patients With Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Confirmed tumor response (CR, PR) rate in 2 consecutive courses within 6 months (Arm I) [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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.

  • Proportion of patients alive at 6 months (Arm II) [ Time Frame: At 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Survival time [ Time Frame: Time from randomization to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.

  • Time to disease progression [ Time Frame: Time from randomization to documentation of disease progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of time to progression will be estimated using the method of Kaplan-Meier.

  • Time to treatment failure [ Time Frame: 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 88
Study Start Date: December 2002
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: bortezomib
Given IV
Experimental: Arm II
Patients receive bortezomib as in arm I and gemcitabine IV over 30 minutes on days 1 and 8.
Drug: bortezomib
Given IV
Drug: gemcitabine hydrochloride
Given IV

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052689

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Steven Alberts North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00052689     History of Changes
Other Study ID Numbers: NCI-2012-01799, NCI-2012-01799, NCCTG-N014C, CDR0000258670, N014C, N014C, U10CA025224
Study First Received: January 24, 2003
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Bortezomib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 14, 2014