Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer
Conditions
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. 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.
Interventions
BIOLOGICALaldesleukin
Given subcutaneously
DRUGbryostatin 1
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed