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

Primary Purpose

Adenocarcinoma of the Gastroesophageal Junction, Diffuse Adenocarcinoma of the Stomach, Intestinal Adenocarcinoma of the Stomach

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
irinotecan
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Gastroesophageal Junction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 esophagogastroduodenoscopy (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

Sites / Locations

  • Montefiore Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Stratum 1 (previously untreated)

Stratum 2 (previously treated)

Arm Description

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.

(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1.

Outcomes

Primary Outcome Measures

True Response Rate Evaluated for the Combination of Irinotecan and PS341 by Response Evaluation Criteria in Solid Tumors (RECIST)
CT or MRI imaging scans of measurable lesions were obtained at baseline and every 8 weeks thereafter. Responses were classified according to RECIST criteria (version 1.0)

Secondary Outcome Measures

Change in Patterns of Gene Expression Pre- and Post-treatment Performed by GeneChip Analysis
Number of Participants with a Change in Gene Expression from Pre to Post Treatment

Full Information

First Posted
June 5, 2003
Last Updated
January 29, 2021
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00061932
Brief Title
Bortezomib With or Without Irinotecan in Treating Patients With Cancer of the Gastroesophageal Junction or Stomach
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stratum 1 (previously untreated)
Arm Type
Experimental
Arm Description
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.
Arm Title
Stratum 2 (previously treated)
Arm Type
Experimental
Arm Description
(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
LDP 341, MLN341, VELCADE
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
irinotecan
Other Intervention Name(s)
Campto, Camptosar, CPT-11, U-101440E
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
True Response Rate Evaluated for the Combination of Irinotecan and PS341 by Response Evaluation Criteria in Solid Tumors (RECIST)
Description
CT or MRI imaging scans of measurable lesions were obtained at baseline and every 8 weeks thereafter. Responses were classified according to RECIST criteria (version 1.0)
Time Frame
Up to 6 years
Secondary Outcome Measure Information:
Title
Change in Patterns of Gene Expression Pre- and Post-treatment Performed by GeneChip Analysis
Description
Number of Participants with a Change in Gene Expression from Pre to Post Treatment
Time Frame
Baseline to 6 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 esophagogastroduodenoscopy (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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allyson Ocean
Organizational Affiliation
Montefiore Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24526575
Citation
Ocean AJ, Christos P, Sparano JA, Shah MA, Yantiss RK, Cheng J, Lin J, Papetti M, Matulich D, Schnoll-Sussman F, Besanceney-Webler C, Xiang J, Ward M, Dilts KT, Keresztes R, Holloway S, Chen EX, Wright JJ, Lane ME. Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach. Invest New Drugs. 2014 Jun;32(3):542-8. doi: 10.1007/s10637-014-0070-0. Epub 2014 Feb 15.
Results Reference
result

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

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