Clinical trial NCT00032188: Interleukin-2 and Bryostatin 1 in Treating Patients With Advanced Kidney Cancer
Official title: A Randomized Phase II Study Of Interluekin-2 In Combination With Three Different Doses Of Bryostatin In Patients With Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall response (CR and PR)
timeFrame: Up to 1 year
measure: Time to disease progression
timeFrame: From the date of registration to the date of progressive disease or death
measure: Overall survival
timeFrame: Up to 1 year
measure: Disease-free survival
timeFrame: Up to 1 year
Secondary outcomes:
measure: All observed toxicities assessed using CTC version 2.0
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Walter Stadler
role: PRINCIPAL_INVESTIGATOR
References: