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

Stage IV Renal Cell Cancer Clinical Trial

Official title:

A Randomized Phase II Study Of Interluekin-2 In Combination With Three Different Doses Of Bryostatin In Patients With Renal Cell Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00032188
• Other study ID #: NCI-2012-02460
• Secondary ID: 11367N01CM17102C
• Status: Completed
• Phase: Phase 2
• First received: March 8, 2002
• Last updated: January 23, 2013
• Start date: January 2002

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Recurrent Renal Cell Cancer
• Stage III Renal Cell Cancer
• Stage IV Renal Cell Cancer

Intervention

Biological:
• aldesleukin
Given subcutaneously

Drug:
• bryostatin 1
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response (CR and PR)	Will be comparing using Fisher's exact test.	Up to 1 year	No
Primary	Time to disease progression	Kaplan-Meier estimates will be generated.	From the date of registration to the date of progressive disease or death	No
Primary	Overall survival	Kaplan-Meier estimates will be generated.	Up to 1 year	No
Primary	Disease-free survival	Will be compared using the logrank test.	Up to 1 year	No
Secondary	All observed toxicities assessed using CTC version 2.0	A chi-square test and one-way ANOVA will be used for categorical and continuous toxicity endpoints, respectively.	Up to 1 year	Yes