PS-341 in Treating Patients With Metastatic Kidney Cancer

A Phase II Trial of PS-341 in Patients With Renal Cell Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which regimen of PS-341 is more effective in treating metastatic kidney cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of PS-341 in treating patients who have metastatic kidney cancer.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: PS-341; Procedure: Tumor Biopsy

Detailed Description

OBJECTIVES:

• Determine the objective response rate in patients with metastatic renal cell cancer treated with bortezomib.
• Determine the time to tumor progression and 1-year survival of patients treated with this drug.
• Determine the toxicity profile of this drug in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bortezomib IV over 3-5 seconds twice weekly on weeks 1 and 2. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo core biopsy.
• Arm II: Patients undergo core biopsy. Patients then receive bortezomib IV as in arm I.

Patients undergo radiologic re-evaluation of measurable lesions. Patients with stable disease or a partial or complete response continue to receive bortezomib in the absence of disease progression or unacceptable toxicity.

Patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 9-14 months.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois, S.C.
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • LaGrange, Illinois, United States, 60525
      • LaGrange Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61602
      • Oncology/Hematology Associates of Central Illinois, P.C.
  • Indiana
    • Fort Wayne, Indiana, United States, 46885-5099
      • Fort Wayne Medical Oncology and Hematology, Inc.
    • South Bend, Indiana, United States, 46617
      • Michiana Hematology/Oncology P.C.
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates, P.L.L.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic renal cell cancer

• Measurable disease

  • At least 2.0 cm in at least 1 dimension by physical exam OR at least 1.0 cm in at least 1 dimension by radiologic exam
  • Single measurable lesion must not be within prior radiotherapy portal

• Tumor lesion amenable to core biopsy

  • At least 1 cm of tumor obtainable

• No active CNS metastatic disease

  • Single previously resected CNS metastasis allowed provided no disease progression 8 weeks after therapy and no longer requiring steroids or antiseizure medications

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier-method contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior immunotherapy or biotherapy allowed

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to 25% or more of bone marrow (i.e., whole pelvis)

Surgery:

• See Disease Characteristics

Other:

• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-Treatment biopsy followed by PS-341 administration; Pre-treatment tumor biopsy followed by 3 cycles of PS-341 given by IV infusion. Each cycle will last 3 weeks. PS-341 will be given 2 times a week for 2 weeks followed by a 'rest' week with no drug. After the 3rd cycle, subjects can continue to receive another 3 cycles of the study drug if their disease has not worsened.	Drug: PS-341; Procedure: Tumor Biopsy
Experimental: PS-341 administration followed by biopsy; 3 cycles of PS-341 given by IV infusion. Each cycle will last 3 weeks. PS-341 will be given 2 times a week for 2 weeks followed by a 'rest' week with no drug. After the 3rd cycle, subjects will have a tumor biopsy and can continue to receive another 3 cycles of the study drug if their disease has not worsened.	Drug: PS-341; Procedure: Tumor Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response Rate of PS-341 in colon cancer	9 weeks

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: October 1, 2001
• Primary Completion (Actual): September 1, 2002
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: October 11, 2001
• First Submitted That Met QC Criteria: June 16, 2003
• First Posted (Estimate): June 17, 2003

Study Record Updates

• Last Update Posted (Estimate): September 5, 2013
• Last Update Submitted That Met QC Criteria: September 4, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: 11049A; UCCRC-11049A; NCI-3291