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

NCT ID: NCT00032188

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31

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.

Conditions

Recurrent Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

aldesleukin

Intervention Type: BIOLOGICAL

Given subcutaneously

bryostatin 1

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

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.

Group Type: EXPERIMENTAL

aldesleukin

Intervention Type: BIOLOGICAL

Given subcutaneously

bryostatin 1

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

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.

Group Type: EXPERIMENTAL

aldesleukin

Intervention Type: BIOLOGICAL

Given subcutaneously

bryostatin 1

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

aldesleukin

Given subcutaneously

Intervention Type: BIOLOGICAL

bryostatin 1

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

IL-2; Proleukin; recombinant human interleukin-2; recombinant interleukin-2; B705008K112; BRYO; Bryostatin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter Stadler

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

11367

Identifier Type: -

Identifier Source: secondary_id

N01CM17102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069267

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02460

Identifier Type: -

Identifier Source: org_study_id