Interleukin-2 and Bryostatin 1 in Treating Patients With Advanced Kidney Cancer

Study Overview
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Brief Summary
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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

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective response rate in patients with advanced renal cell carcinoma treated with interleukin-2 (IL-2) and bryostatin 1. II. 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.

Official Title
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A Randomized Phase II Study Of Interluekin-2 In Combination With Three Different Doses Of Bryostatin In Patients With Renal Cell Carcinoma

Conditions
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Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Biological: aldesleukin
* Drug: bryostatin 1
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed renal cell carcinoma Recurrent or refractory advanced disease Newly diagnosed disease with no appropriate standard therapy available Measurable disease No active CNS metastases Single prior CNS metastasis allowed if all of the following are true: Previously resected and irradiated No evidence of progressive CNS disease for at least 8 weeks after completion of therapy No requirement for steroids or anti-seizure medications Performance status - ECOG 0-2 More than 3 months WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST/ALT no greater than 2.5 times ULN Creatinine no greater than 2.0 mg/dL No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test 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 No concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study entry No prior interleukin-2 See Disease Characteristics See Disease Characteristics Prior radiotherapy to less than 50% of bone marrow allowed At least 4 weeks since prior radiotherapy See Disease Characteristics No other concurrent investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (aldesleukin and lowest dose bryostatin 1)<br>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<br>* Given subcutaneously<br>* Other names: recombinant interleukin-2;Drug: bryostatin 1<br>* Given IV<br>* Other names: Bryostatin;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm II (aldesleukin and middle dose bryostatin 1)<br>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<br>* Given subcutaneously<br>* Other names: recombinant interleukin-2;Drug: bryostatin 1<br>* Given IV<br>* Other names: Bryostatin;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm III (aldesleukin and highest dose bryostatin 1)<br>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<br>* Given subcutaneously<br>* Other names: recombinant interleukin-2;Drug: bryostatin 1<br>* Given IV<br>* Other names: Bryostatin;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response (CR and PR) | Will be comparing using Fisher's exact test. | Up to 1 year | 
| Time to disease progression | Kaplan-Meier estimates will be generated. | From the date of registration to the date of progressive disease or death | 
| Overall survival | Kaplan-Meier estimates will be generated. | Up to 1 year | 
| Disease-free survival | Will be compared using the logrank test. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All observed toxicities assessed using CTC version 2.0 | A chi-square test and one-way ANOVA will be used for categorical and continuous toxicity endpoints, respectively. | Up to 1 year |