Gemcitabine, Cisplatin, Plus Lenalidomide as First-line Therapy for Patients With Metastatic Urothelial Carcinoma

NCT01342172 | Terminated Phase 1 Results DMC

• 1 other identifier: GCO 10-1339
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objectives of this study are (Phase 1) to determine in subjects with unresectable or metastatic bladder cancer who have never had chemotherapy, the dose of lenalidomide that is well-tolerated when given in combination with gemcitabine plus cisplatin and (Phase 2) to study this recommended dose in subjects to evaluate progression-free survival at 1 year. The secondary objectives will be to determine the objective response rate to treatment, and the safety of combination therapy with gemcitabine, cisplatin and lenalidomide as well as to evaluate lenalidomide as maintenance treatment in subjects achieving objective response or stable disease.

Conditions

Urinary Bladder Neoplasms

Keywords

Bladder Cancer; Urothelial Cancer; Chemotherapy; First-line; Metastatic

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Lenalidomide

  MTD was determined by testing planned increasing doses up to 25 mg daily dose on days 1-14, starting at 10mg. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. DLTs were defined as any lenalidomide-related Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) Grade 3 or 4 adverse events

  after 1 cycle (each cycle is 21 days)

• Phase II: Progression-free Survival at 1 Year

  1 year

Secondary Outcomes (5)

• The Objective Response Rate to Treatment With Gemcitabine, Cisplatin, Plus Lenalidomide

  After 2 cycles (a cycle is 21 days)

• Number of Grade >=3 Adverse Events

  Day 1 and Day 8 of each treatment cycle; 21 days after the last dose of Lenalidomide

• Best Overall Response

  168 days

• To Determine the Impact of Treatment on Peripheral Blood Immune Cell Subsets

  Day 1 of Cycle 0 and Day 1 of Cycle 2 (each Cycle is 21 days)

• To Determine the Impact of Treatment on Circulating Tumor Cells

  Day 1 of Cycles 0, 1 and 2 (each Cycle is 21 days)

Study Arms (1)

Lenalidomide

EXPERIMENTAL

capsules for oral administration

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

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 successive cohorts during the phase Ib portion 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 orally on days 1-21 of each 28-day cycle. Treatment will continue, in the absence of prohibitive toxicity, until the time of disease progression.

Also known as: Revlimid

Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age \> 18 years at the time of consent.
• Karnofsky Performance Status of ≥ 70%.
• Histological or cytological proof of transitional cell carcinoma of the urothelial tract. The primary site may include: urethra, bladder, ureters, and renal pelvis. Patients with mixed histologies may be enrolled provided that transitional cell carcinoma is the predominant histology.
• Measurable disease according to RECIST or unresectable disease (cT4b).
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
• Females of childbearing potential (FCBP)\* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
• Adequate organ function as determined by the following laboratory values:
• Hemoglobin (Hgb) \> 9 g/dL
• Platelets \> 100 x 1,000,000,000/L
• Absolute neutrophil count (ANC) \> 1.5 x 1,000,000,000/L
• Calculated creatinine clearance of \> 60 cc/min using the Cockcroft-Gault formula
• Bilirubin \< 1.5 x ULN
• Aspartate aminotransferase (AST, SGOT) \< 1.5 X ULN (\< 5 X ULN if patient has hepatic metastases)

You may not qualify if:

• Has had prior treatment with systemic chemotherapy for metastatic disease (prior intravesical therapy is permitted; prior neoadjuvant/adjuvant chemotherapy permitted if completed ≥ 1 year from study entry)
• Has received prior lenalidomide.
• Has had major surgery within 30 days of starting the study treatment
• Has had any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
• Has active CNS metastases. Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
• Has a history of a prior malignancy
• Has received anticancer therapy, radiation, or any investigational agent within 30 days prior to being registered for protocol therapy.
• Pregnant or breastfeeding.
• Has a clinically significant infection as judged by the treating investigator.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Celgene: collaborator

Study Sites (3)

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Agarwal N, Apolo AB, Tsao CK, Lee KM, Godbold JH, Soto R, Poole A, Gimpel-Tetra K, Lowe N, Oh WK, Galsky MD. Phase Ib/II trial of gemcitabine, cisplatin, and lenalidomide as first-line therapy in patients with metastatic urothelial carcinoma. Oncologist. 2014 Sep;19(9):915-6. doi: 10.1634/theoncologist.2014-0153. Epub 2014 Jul 22.

  PMID: 25052451 RESULT

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplasm Metastasis

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

The trial was terminated because the regimen was deemed poorly tolerated for chronic administration because of the need for repeated dose delays and reductions coupled with slow accrual.

Results Point of Contact

• Title: Dr. Matthew Galsky
• Organization: Icahn School of Medicine at Mount Sinai

matthew.galsky@mssme.edu

212-241-8816

Study Officials

• Matthew Galsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 21, 2011
• First Posted: April 27, 2011
• Study Start: March 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: April 23, 2019
• Results First Posted: November 26, 2014

Record last verified: 2019-04

Locations

US (3)