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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00061932
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 127
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	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	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

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

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Study Start Date: Apr 1, 2003
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stratum 1 (previously untreated) 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; Given IV; Other Names: Campto Camptosar CPT-11 U-101440E
Experimental: Stratum 2 (previously treated) (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

Outcome Measures

Primary Outcome Measures

1. True Response Rate Evaluated for the Combination of Irinotecan and PS341 by Response Evaluation Criteria in Solid Tumors (RECIST) [Up to 6 years]

   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

1. Change in Patterns of Gene Expression Pre- and Post-treatment Performed by GeneChip Analysis [Baseline to 6 years]

   Number of Participants with a Change in Gene Expression from Pre to Post Treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center	Bronx	New York	United States	10467-2490

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Allyson Ocean, Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00061932
• Other Study ID Numbers: NCI-2012-03015; N01CM62204
• First Posted: Jun 6, 2003
• Last Update Posted: Feb 2, 2021
• Last Verified: Jan 1, 2021

• Additional relevant MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Irinotecan; Bortezomib

Study Results

Participant Flow

Recruitment Details	A total of 41 patients were enrolled from 6 institutions between April 2003 and September 2006

Arm/Group Title	Stratum 1 (Previously Untreated)	Stratum 2 (Previously Treated)
Arm/Group Description	Patients receive bortezomib IV 1.3 mg/m2 over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV 125 mg/m2 over 90 minutes on days 1 and 8. bortezomib: Given IV (1.3 mg/m2) irinotecan: Given IV (125 mg/m2)	(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1. bortezomib: Given IV irinotecan: Given IV
Period Title: Overall Study
STARTED	29	12
COMPLETED	16	8
NOT COMPLETED	13	4

Baseline Characteristics

Arm/Group Title	Stratum 1 (Previously Untreated)	Stratum 2 (Previously Treated)	Total
Arm/Group 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. bortezomib: Given IV irinotecan: Given IV	(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1. bortezomib: Given IV irinotecan: Given IV	Total of all reporting groups
Overall Participants	29	12	41
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58.5	54.5	56.5
Sex: Female, Male (Count of Participants)
Female	7 24.1%	7 58.3%	14 34.1%
Male	22 75.9%	5 41.7%	27 65.9%
Race/Ethnicity, Customized (participants) [Number]
White	24 82.8%	9 75%	33 80.5%
Asian	2 6.9%	2 16.7%	4 9.8%
Black	3 10.3%	0 0%	3 7.3%
Unknown	0 0%	1 8.3%	1 2.4%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stratum 1 (Previously Untreated)	Stratum 2 (Previously Treated)
Arm/Group 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. bortezomib: Given IV irinotecan: Given IV	(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1. bortezomib: Given IV irinotecan: Given IV
Measure Participants	29	12
Number (95% Confidence Interval) [participants]	3 10.3%	1 8.3%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stratum 1 (Previously Untreated)	Stratum 2 (Previously Treated)
Arm/Group Description	Patients receive bortezomib IV 1.3 mg/m2 over 3-5 seconds on days 1, 4, 8, and 11 and irinotecan IV 125 mg/m2 over 90 minutes on days 1 and 8. bortezomib: Given IV (1.3 mg/m2) irinotecan: Given IV (125 mg/m2)	(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1. bortezomib: Given IV irinotecan: Given IV
Measure Participants	10	2
Count of Participants [Participants]	2 6.9%	2 16.7%

Adverse Events

Arm/Group Title	Stratum 1 (Previously Untreated)		Stratum 2 (Previously Treated)
Arm/Group 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. bortezomib: Given IV irinotecan: Given IV		(closed to accrual as of 9/19/2006): Patients receive bortezomib as in stratum 1. bortezomib: Given IV irinotecan: Given IV
All Cause Mortality
	Stratum 1 (Previously Untreated)		Stratum 2 (Previously Treated)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Stratum 1 (Previously Untreated)		Stratum 2 (Previously Treated)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/29 (82.8%)		8/12 (66.7%)
Blood and lymphatic system disorders
Anemia	5/29 (17.2%)	5	1/12 (8.3%)	1
Febrile neutropenia	4/29 (13.8%)	4	0/12 (0%)	0
Cardiac disorders
Heart stoppage	1/29 (3.4%)	1	0/12 (0%)	0
Cardiac ischemia/infarction	1/29 (3.4%)	1	0/12 (0%)	0
Gastrointestinal disorders
Anorexia	1/29 (3.4%)	1	1/12 (8.3%)	1
Dehydration	5/29 (17.2%)	5	3/12 (25%)	3
Diarrhea	8/29 (27.6%)	8	0/12 (0%)	0
Abdominal distension	0/29 (0%)	0	1/12 (8.3%)	1
Malabsorption	0/29 (0%)	0	1/12 (8.3%)	1
Nausea	5/29 (17.2%)	5	1/12 (8.3%)	1
Obstruction: Small bowel NOS	4/29 (13.8%)	4	1/12 (8.3%)	1
Abdominal pain	3/29 (10.3%)	3	1/12 (8.3%)	1
Vomiting	6/29 (20.7%)	6	1/12 (8.3%)	1
General disorders
Edema: trunk/genital	0/29 (0%)	0	1/12 (8.3%)	1
Fatigue	5/29 (17.2%)	5	1/12 (8.3%)	1
Infections and infestations
Infection: Lung	0/29 (0%)	0	1/12 (8.3%)	1
Investigations
Leukocytopenia	8/29 (27.6%)	8	0/12 (0%)	0
Neutropenia	8/29 (27.6%)	8	0/12 (0%)	0
Thrombocytopenia	3/29 (10.3%)	3	2/12 (16.7%)	2
Metabolism and nutrition disorders
Hypoalbuminemia	4/29 (13.8%)	4	0/12 (0%)	0
Hypocalcemia	2/29 (6.9%)	2	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Pain: right hip	0/29 (0%)	0	1/12 (8.3%)	1
Renal and urinary disorders
Hemorrhage, GU: Urinary NOS	0/29 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/29 (0%)	0	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Rash: desquamation	2/29 (6.9%)	2	0/12 (0%)	0
Vascular disorders
Hypotension	2/29 (6.9%)	2	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Stratum 1 (Previously Untreated)		Stratum 2 (Previously Treated)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/29 (86.2%)		10/12 (83.3%)
Gastrointestinal disorders
Flatulence	4/29 (13.8%)	4	0/12 (0%)	0
Constipation	5/29 (17.2%)	5	5/12 (41.7%)	5
General disorders
Fever (in the absence of neutropenia)	3/29 (10.3%)	3	0/12 (0%)	0
Chills	4/29 (13.8%)	4	0/12 (0%)	0
Edema:limbs	4/29 (13.8%)	4	3/12 (25%)	3
Nervous system disorders
Neuropathy: Sensory	4/29 (13.8%)	4	0/12 (0%)	0
Psychiatric disorders
Insomnia	3/29 (10.3%)	3	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	3/29 (10.3%)	3	1/12 (8.3%)	1
Rash: desquamation	3/29 (10.3%)	3	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.