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Bortezomib With or Without Irinotecan in Treating Patients With Cancer of the Gastroesophageal Junction or Stomach

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00061932
First received: June 5, 2003
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

This phase II trial is studying how well bortezomib with or without irinotecan works in treating patients with gastroesophageal junction or stomach cancer that can not be removed by surgery. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy such as irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with irinotecan may kill more tumor cells.


Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Diffuse Adenocarcinoma of the Stomach
Intestinal Adenocarcinoma of the Stomach
Mixed Adenocarcinoma of the Stomach
Recurrent Gastric Cancer
Stage IIIB Gastric Cancer
Stage IIIC Gastric Cancer
Stage IV Gastric Cancer
Drug: bortezomib
Drug: irinotecan hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of PS-341 Alone or in Combination With Irinotecan in Patients With Adenocarcinoma of the Gastroesophageal Junction (GEJ) or Stomach

Resource links provided by NLM:


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

Primary Outcome Measures:
  • True response rate evaluated for the combination of irinotecan and PS341 by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in patterns of gene expression pre- and post-treatment performed by GeneChip analysis [ Time Frame: Baseline to 6 years ] [ Designated as safety issue: No ]

Enrollment: 58
Study Start Date: April 2003
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stratum 1 (previously untreated patients)
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Other: laboratory biomarker analysis
Correlative studies
Experimental: Stratum 2 (previously treated patients)
(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the response rate for the combination of irinotecan and PS 341 in patients with previously untreated adenocarcinoma of the stomach or GEJ.

II. To determine the response rate for PS341 in patients with previously treated adenocarcinoma of the stomach or GEJ.

III. To determine the toxicities and recovery from toxicities for patients receiving PS 341 alone or in combination with irinotecan IV. To perform GeneChip analysis on biopsy specimens prior to and subsequent to treatment with PS341 to determine changes in patterns of gene expression

OUTLINE: Patients are stratified (stratum 2 closed to accrual as of 9/19/2006) according to prior chemotherapy for advanced disease (yes vs no).

STRATUM 1 (Previously untreated patients): Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV over 90 minutes on days 1 and 8.

STRATUM 2 (Previously treated patients) (closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1.

In both strata, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed adenocarcinoma of the GE junction or stomach, which is beyond the scope of surgical resection
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • Patients may have received adjuvant therapy for resected disease

    • Patients who have received no prior systemic therapy for advanced disease are eligible to receive PS341 + irinotecan
    • Patients are eligible for PS-341 as a single agent if they have received any number of prior regimens for gastric cancer
  • Life expectancy of greater than 6 weeks
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >=100,000/uL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits
  • When possible, patients will undergo an esophagogastroduodenscopy (EGD) with biopsy prior to therapy then at 24 hours after starting PS-341
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents, concurrent radiation therapy, or other chemotherapy; patients who have had photodynamic therapy either within 4 weeks of study entry or concurrently are ineligible, unless it was used to relieve esophageal obstruction that could not be treated with laser, stent or dilatation
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PS 341 or other agents used in the study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PS341
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
  • Patients with a concurrent malignancy are excluded (except for early stage squamous cell carcinoma of the skin or cervix which can be treated locally); patients with an advanced malignancy within the past five years are not eligible; patients with a prior malignancy who have been disease free for five years are eligible
  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: NCT00061932

Locations
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
Investigators
Principal Investigator: Allyson Ocean Montefiore Medical Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00061932     History of Changes
Other Study ID Numbers: NCI-2012-03015, 0103672, N01CM62204, N01CM62203
Study First Received: June 5, 2003
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Stomach Diseases
Bortezomib
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 19, 2014