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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

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

Treatments: Biological: aldesleukin; Other: laboratory biomarker analysis; Drug: bryostatin 1

Study type: Interventional

Funder types: NIH

Identifiers

NCT00032188

N01CM17102 (U.S. NIH Grant/Contract)

NCI-2012-02460

11367

CDR0000069267 (Registry Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 65 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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65 participants in 3 patient groups

Arm I (aldesleukin and lowest dose bryostatin 1)

Experimental group

Description:

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.

Treatment:

Drug: bryostatin 1

Biological: aldesleukin

Other: laboratory biomarker analysis

Arm II (aldesleukin and middle dose bryostatin 1)

Experimental group

Description:

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.

Treatment:

Drug: bryostatin 1

Biological: aldesleukin

Other: laboratory biomarker analysis

Arm III (aldesleukin and highest dose bryostatin 1)

Experimental group

Description:

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.

Treatment:

Drug: bryostatin 1

Biological: aldesleukin

Other: laboratory biomarker analysis