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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00032188
First received: March 8, 2002
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage III Renal Cell Cancer
Stage IV Renal Cell Cancer
Biological: aldesleukin
Drug: bryostatin 1
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study Of Interluekin-2 In Combination With Three Different Doses Of Bryostatin In Patients With Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response (CR and PR) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be generated.

  • Overall survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be generated.

  • Disease-free survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Will be compared using the logrank test.


Secondary Outcome Measures:
  • All observed toxicities assessed using CTC version 2.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
    A chi-square test and one-way ANOVA will be used for categorical and continuous toxicity endpoints, respectively.


Enrollment: 65
Study Start Date: January 2002
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: aldesleukin
Given subcutaneously
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin
Other: laboratory biomarker analysis
Correlative studies
Experimental: 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.
Biological: aldesleukin
Given subcutaneously
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin
Other: laboratory biomarker analysis
Correlative studies
Experimental: 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.
Biological: aldesleukin
Given subcutaneously
Other Names:
  • IL-2
  • Proleukin
  • recombinant human interleukin-2
  • recombinant interleukin-2
Drug: bryostatin 1
Given IV
Other Names:
  • B705008K112
  • BRYO
  • Bryostatin
Other: laboratory biomarker analysis
Correlative studies

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00032188

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
Investigators
Principal Investigator: Walter Stadler University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00032188     History of Changes
Other Study ID Numbers: NCI-2012-02460, 11367, N01CM17102, CDR0000069267
Study First Received: March 8, 2002
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bryostatin 1
Aldesleukin
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Adjuvants, Immunologic
Immunologic Factors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 17, 2014