Gemcitabine, Cisplatin, and Lenalidomide for Bladder Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01441050
First received: September 24, 2011
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

Background:

- Gemcitabine and cisplatin are common drugs for bladder cancer. Lenalidomide is a drug that limits a tumor s ability to form new blood vessels. By limiting new blood vessel growth, lenalidomide may improve the other drugs ability to shrink tumors or stop their growth. Researchers are interested in seeing how safe and effective this new drug combination is in treating bladder cancer.

Objectives:

- To test the safety and effectiveness of lenalidomide, gemcitabine, and cisplatin for bladder cancer.

Eligibility:

- Individuals at least 18 years of age who have bladder cancer that has not been treated with chemotherapy (excluding chemotherapy given right before or right after surgery to remove the bladder).

Design:

  • Participants will be screened with a medical history, physical exam, blood and urine tests, and imaging studies.
  • This study has two separate parts. All participants will have frequent blood tests and imaging studies.
  • In the first part, participants will have gemcitabine, cisplatin, and different doses of lenalidomide to find the safest and most effective dose. The chemotherapy will be given in 21-day cycles of treatment, for up to six cycles of treatment.
  • After the end of six cycles, participants whose tumors respond to the drugs will have lenalidomide alone for 28-day cycles (21 days on the drug and 7 days off). Treatment will continue for as long as it is effective.
  • In the second part, participants will receive lenalidomide alone for one 21-day cycle and then all three drugs for up to six more 21-day cycles. This part will determine how well the drugs can shrink bladder cancers.

Condition Intervention Phase
Ureteral Neoplasms
Urinary Bladder Neoplasms
Urethral Neoplasms
Drug: Lenalidomide
Drug: Cisplatin
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-Center Phase 1B/II Trial of Gemcitabine, Cisplatin, Plus Lenalidomide as First Line Therapy for Patients With Metastatic Urothelial Carcinoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Determine optimal dose of gemcitabine, cisplatin, and lenalidomide. [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]
  • Determine the 1 year progression-free survival on combination. [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response rate by RECIST of gem, cis, lenalidomide combination; safety of combination per CTCAE; evaluate lenalidomide as maintenance treatment; treatment impact on peripheral immune cell subsets and circulating tumos cells. [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]
  • Safety of combination per CTCAE. [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]
  • Evaluate lenalidomide as maintenance treatment. [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]
  • Treatment impact on peripheral immune cell subsets and circulating tumos cells. [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: July 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Lenalidomide
    N/A
    Drug: Cisplatin
    N/A
    Drug: Gemcitabine
    N/A
  Hide Detailed Description

Detailed Description:

Background

  • Urothelial carcinoma of the urinary bladder is the second most common genitourinary malignancy. Each year in the United States, more than 60,000 patients will develop urothelial carcinoma and over 12,000 will die of their disease.
  • Gemcitabine plus cisplatin is standard first-line therapy in patients with metastatic urothelial carcinoma. While treatment of this patient population has been made more tolerable over the past 20 years, there have been no improvements in efficacy.
  • Lenalidomide has both anti-angiogenic and potent immunomodulatory properties, and has been safely coadministered with cytotoxic therapy in patients with solid tumors and non-clinical studies demonstrate possible synergy with gemcitabine.

Objectives

  • To determine the recommended phase II dose of gemcitabine, cisplatin, and lenalidomide.
  • To determine the 1 year progression-free survival in patients with advanced/metastatic urothelial carcinoma treated with gemcitabine, cisplatin, plus lenalidomide.

Eligibility

  • Patients greater than or equal to 18 years of age with histological or cytological confirmation of transitional cell carcinoma of the urothelial tract (urethra, bladder, ureters, or renal pelvis), who have measurable disease or unresectable disease (cT4b).
  • Must be registered with the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist .
  • Safety laboratory values and performance status must meet specified limits. Females of childbearing potential must have a negative serum or urine pregnancy test. Males and females must be will to use effective birth control measures (when applicable).
  • Must be able to take aspirin.
  • May not have had prior treatment with systemic chemotherapy for metastatic disease, prior lenalidomide, or surgery (within 30 days of starting study treatment).
  • HIPAA authorization for the release of personal health information is not required for subjects participating at NCI

Design

Phase Ib

-Patients will receive gemcitabine 1000 mg/m2 IV on days 1 + 8 and cisplatin 70 mg/m2 IV on day 1 of each 21 day cycle. Lenalidomide will be given orally on days 1-14 and the dose will be escalated in four successive cohorts (10 mg, 15 mg, 20 mg, 25 mg) to define the recommended phase II dose. Patients will continue gemcitabine, cisplatin, plus lenalidomide for up to 6 cycles, in the absence of disease progression or prohibitive toxicity. After completion of 6 cycles of therapy, patients who have achieved at least stable disease will proceed with maintenance lenalidomide given at patient's phase 1b dose level orally on days 1-21 of each 28-day cycle.

Phase II

  • During cycle 1 only of the phase II portion, subjects will have a lead-in period where lenalidomide will be administered orally as a single-agent at 10 mg once per day, the dose defined from the phase Ib portion of the study, for 14 consecutive days followed by 7 days of rest(for a total lead-in period of 21 days) prior to starting combination treatment.
  • Patients will receive gemcitabine 1000 mg/m2 IV on days 1 + 8 and cisplatin 70 mg/m(2) IV on day 1 of each 21 day cycle starting with cycle 2. Lenalidomide will be given orally on days 1-14 at 10 mg once per day, the dose defined from the phase Ib portion of the study. Patients will continue gemcitabine, cisplatin, plus lenalidomide for up to 6 cycles, in the absence of disease progression or prohibitive toxicity. After completion of 6 cycles of therapy, patients who have achieved at least stable disease will proceed with maintenance lenalidomide given orally at 10 mg once per day on days 1-21 of each 28-day cycle.
  • A CT scan of the chest, abdomen, and pelvis will be performed after every 2 cycles (or sooner if there is evidence of disease progression) while on combination therapy until disease progression. At the NCI site, subjects enrolled in phase Ib will be assessed after cycles 2, 4 and 6 while those enrolled in phase II, which features the cycle 1 lead in , will be assessed after cycles 3, 5, and 7. During the maintenance phase CT scans will be performed after every 3 cycles.
  • The phase II portion will be conducted using a single-stage, single-arm, design. The primary endpoint will be Progression Free Survival (PFS) at one year. Data indicate that patients treated with gemcitabine and cisplatin experience 28% PFS at 1-year. The goal is to see if the addition of lenalidomide will increase PFS by an absolute amount of 20%, i.e., from 28% to 48%.
  • Approximately 12-15 patients will be enrolled in the phase 1b portion and approximately 43 patients will be enrolled in the phase II portion for a total of 67 patients. Enrollment will proceed for approximately 36 months. 15 - 20 patients will be enrolled at the NCI, NIH.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION AND EXCLUSION CRITERIA:
  • Patients greater than or equal to 18 years of age with histological or cytological confirmation of transitional cell carcinoma of the urothelial tract (urethra, bladder, ureters, or renal pelvis), who have measurable disease or unresectable disease (cT4b).
  • Must be registered with the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist .
  • Safety laboratory values and performance status must meet specified limits.
  • Females of childbearing potential must have a negative serum or urine pregnancy test.
  • Males and females must be will to use effective birth control measures (when applicable).
  • Must be able to take aspirin.
  • May not have had prior treatment with systemic chemotherapy for metastatic disease, prior lenalidomide, or surgery (within 30 days of starting study treatment).
  • HIPAA authorization for the release of personal health information is not required for subjects participating at NCI
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441050

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Andrea B Apolo, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01441050     History of Changes
Other Study ID Numbers: 110227, 11-C-0227
Study First Received: September 24, 2011
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Bladder
Renal Pelvis
Ureter
Urethra
Transitional Cell Carcinoma
Bladder Cancer
Ureteral Cancer

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Ureteral Neoplasms
Urethral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Ureteral Diseases
Urethral Diseases
Gemcitabine
Lenalidomide
Cisplatin
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 17, 2014