A Randomized Phase II Study Of Interluekin-2 In Combination With Three Different Doses Of Bryostatin In Patients With Renal Cell Carcinoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Overall response (CR and PR)
Study Overview
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
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: aldesleukin (Biological)
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.
Intervention: bryostatin 1 (Drug)
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.
Intervention: laboratory biomarker analysis (Other)
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.
Intervention: aldesleukin (Biological)
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.
Intervention: bryostatin 1 (Drug)
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.
Intervention: laboratory biomarker analysis (Other)
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.
Intervention: aldesleukin (Biological)
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.
Intervention: bryostatin 1 (Drug)
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.
Intervention: laboratory biomarker analysis (Other)
Outcomes
Primary Outcomes
Overall response (CR and PR)
Time Frame: Up to 1 year
Will be comparing using Fisher's exact test.
Time to disease progression
Time Frame: From the date of registration to the date of progressive disease or death
Kaplan-Meier estimates will be generated.
Overall survival
Time Frame: Up to 1 year
Kaplan-Meier estimates will be generated.
Disease-free survival
Time Frame: Up to 1 year
Will be compared using the logrank test.
Secondary Outcomes
- All observed toxicities assessed using CTC version 2.0(Up to 1 year)