Interleukin-2 and Bryostatin 1 in Treating Patients With Advanced Kidney Cancer
Study Details
Study Description
Brief Summary
Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining bryostatin 1 with interleukin-2 may cause a stronger immune response and kill more tumor cells. Randomized phase II trial to study the effectiveness of combining interleukin-2 and bryostatin 1 in treating patients who have advanced kidney cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
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Determine the objective response rate in patients with advanced renal cell carcinoma treated with interleukin-2 (IL-2) and bryostatin 1.
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Compare the toxicity of 3 different doses of bryostatin 1 given in combination with a fixed dose of IL-2 in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of three dose levels of bryostatin 1.
ARM I: Patients receive interleukin-2 (IL-2) subcutaneously on days 1-4, 8-11, and 15-18. For the second and subsequent courses of IL-2, patients also receive lowest dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive IL-2 as in arm I and middle dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive IL-2 as in arm I and highest dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity.
Patients with stable or responding disease may receive 3 additional courses of therapy. An additional cohort of patients receives treatment as above at a higher dose to evaluate toxicity.
Patients are followed for 1 year.
PROJECTED ACCRUAL: A total of 24-65 patients (8-16 per bryostatin 1 dose level) will be accrued for this study within 14-27 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I (aldesleukin and lowest dose bryostatin 1) Patients receive IL-2 subcutaneously on days 1-4, 8-11, and 15-18. For the second and subsequent courses of IL-2, patients also receive lowest dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. |
Biological: aldesleukin
Given subcutaneously
Other Names:
Drug: bryostatin 1
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
| Experimental: Arm II (aldesleukin and middle dose bryostatin 1) Patients receive IL-2 subcutaneously on days 1-4, 8-11, and 15-18. For the second and subsequent courses of IL-2, patients also receive middle dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. |
Biological: aldesleukin
Given subcutaneously
Other Names:
Drug: bryostatin 1
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
| Experimental: Arm III (aldesleukin and highest dose bryostatin 1) Patients receive IL-2 subcutaneously on days 1-4, 8-11, and 15-18. For the second and subsequent courses of IL-2, patients also receive highest dose bryostatin 1 IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. |
Biological: aldesleukin
Given subcutaneously
Other Names:
Drug: bryostatin 1
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Overall response (CR and PR) [Up to 1 year]
Will be comparing using Fisher's exact test.
- Time to disease progression [From the date of registration to the date of progressive disease or death]
Kaplan-Meier estimates will be generated.
- Overall survival [Up to 1 year]
Kaplan-Meier estimates will be generated.
- Disease-free survival [Up to 1 year]
Will be compared using the logrank test.
Secondary Outcome Measures
- All observed toxicities assessed using CTC version 2.0 [Up to 1 year]
A chi-square test and one-way ANOVA will be used for categorical and continuous toxicity endpoints, respectively.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed renal cell carcinoma
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Recurrent or refractory advanced disease
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Newly diagnosed disease with no appropriate standard therapy available
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Measurable disease
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No active CNS metastases
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Single prior CNS metastasis allowed if all of the following are true:
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Previously resected and irradiated
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No evidence of progressive CNS disease for at least 8 weeks after completion of therapy
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No requirement for steroids or anti-seizure medications
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Performance status - ECOG 0-2
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More than 3 months
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WBC at least 3,000/mm^3
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Absolute neutrophil count at least 1,500/mm^3
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Platelet count at least 100,000/mm^3
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Bilirubin no greater than 1.5 times upper limit of normal (ULN)
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AST/ALT no greater than 2.5 times ULN
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Creatinine no greater than 2.0 mg/dL
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No symptomatic congestive heart failure
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No unstable angina pectoris
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No cardiac arrhythmia
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective barrier contraception during and for at least 2 weeks after study for female patients and for 3 months after study for male patients
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No concurrent uncontrolled illness
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No ongoing or active infection
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No psychiatric illness or social situation that would preclude study entry
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No prior interleukin-2
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See Disease Characteristics
-
See Disease Characteristics
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Prior radiotherapy to less than 50% of bone marrow allowed
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At least 4 weeks since prior radiotherapy
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See Disease Characteristics
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No other concurrent investigational agents
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No concurrent combination antiretroviral therapy for HIV-positive patients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637-1470 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Walter Stadler, University of Chicago Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-02460
- 11367
- N01CM17102
- CDR0000069267