Gemcitabine, Carboplatin, and Lenalidomide for Treatment of Advanced/Metastatic Urothelial Cancer and Other Solid Tumors

NCT01352962 | Completed Phase 1 FDA Drug

• 2 other identifiers: 11014011-C-0140
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Gemcitabine and carboplatin are chemotherapy drugs used to treat several types of cancer, including cancer of the pancreas, bladder, ovaries, and lung. Lenalidomide, a drug that prevents the growth of new blood vessels in tumors, has been approved for treatment of certain blood cancers, but it has not yet been approved for use in combination with gemcitabine and carboplatin. Researchers are interested in determining the safest and most effective dose of this combined form of chemotherapy for solid tumors, particularly for urothelial cancer (tumors of the bladder, urethra, ureter, or renal pelvis). Objectives:

• To evaluate the safety and effectiveness of combined lenalidomide, gemcitabine, and carboplatin as a treatment for solid tumor cancers.
• To evaluate the safety and effectiveness of combined lenalidomide, gemcitabine, and carboplatin as a treatment for urothelial (bladder) cancer. Eligibility:
• Individuals at least 18 years of age who have been diagnosed with solid tumors that have not responded to standard treatments.
• Individuals at least 18 years of age who have been diagnosed with urothelial cancer that has not responded to standard treatments. Design:
• Participants will be screened with a physical examination, medical history, blood tests, and tumor imaging studies.
• Participants with urothelial cancer will receive lenalidomide alone for the first 14 days of a 21-day cycle before starting the first full treatment cycle.
• All participants will receive gemcitabine on days 1 and 8, and carboplatin on day 1 only, of every 21-day treatment cycle. Lenalidomide will be taken daily at home for the first 14 days of each cycle. Participants will be asked to take aspirin or other medications to prevent the possibility of blood clots.
• Participants may receive up to six cycles of treatment with this combination. If after six cycles the cancer has not grown or has shrunk, participants may continue to take lenalidomide alone for an additional 6 months (total of 12 months of therapy) or until the cancer recurs.
• Participants will be monitored with blood samples, physical examinations, and tumor imaging studies through the cycles of treatment.
• After the end of the last treatment cycle, participants will have followup visits every 3 months for the next 18 months, then every 6 months for another 18 months, and then yearly.

Conditions

Urethral Neoplasms; Neoplasms, Urethral; Cancer of the Urethra; Urethral Cancer

Keywords

Dose Limiting Toxicity; Urethra Cancer; Carcinoma of the Bladder; Cancer of the Renal Pelvis; Ureter Cancer; Urethral Cancer; Solid Tumor; Pancreatic Cancer; Ovarian Cancer; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• dose limiting toxicity (DLT)

  any grade 3 or 4 toxicity with exceptions listed in protocol; MTD is one dose level below the dose that induces DLT in more than 1/6 patients

  Maximum Tolerated Dose (MTD)

Secondary Outcomes (4)

• response rate

  every 3 months for the first 18 months, every 6 months for the subsequent 18 months, then yearly

• progression free survival

  every 3 months for the first 18 months, every 6 months for the subsequent 18 months, then yearly

• overall survival

  every 3 months for the first 18 months, every 6 months for the subsequent 18 months, then yearly

• effects of treatment on Treg, sIL-2R, VEGF, CTC and CEC

  baseline, lead-in day 8, lead-in day 14 and C1D8

Study Arms (2)

Arm 1

EXPERIMENTAL

Standard of Care plus escalating doses of Lenalidomide

Drug: Gemcitabine; Drug: Carboplatin; Drug: Lenalidomide

Arm 2

EXPERIMENTAL

Lenalidomide Lead for 14 days + standard of care + lenalidomide MTD

Drug: Gemcitabine; Drug: Carboplatin; Drug: Lenalidomide

Interventions

Gemcitabine DRUG

1,000mg/m2 IVPB over 30 min x 1

Arm 1; Arm 2

Carboplatin DRUG

AUC 5\*\* IVPB over 30 min x 1

Arm 1; Arm 2

Lenalidomide DRUG

Escalating Doses starting at 2.5 po daily up to 25 mg po daily until MTD is reached.

Arm 1; Arm 2

Eligibility Criteria

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

You may qualify if:

• Dose Escalation cohort only
• \- Adult patients with histologic documentation of an advanced solid tumor for whom gemcitabine and carboplatin would be appropriate first line therapy, including but not limited to urothelial cancer, non-small cell lung cancer, pancreatic and ovarian carcinoma.
• Expansion cohort only
• Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. Confirmation may be obtained from any CLIA certified lab.
• Patient must have a histologically confirmed diagnosis of non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis including but not limited to squamous cell, neuroendocrine, adenocarcinoma including urachal and sarcomatoid. Confirmation may be obtained from any CLIA certified lab.
• All patients
• Unresectable or metastatic disease
• Urothelial cancer patients should be ineligible for cisplatin based on one or more of the following:
• Calculated creatinine clearance of \< 60 mL/min (but greater than or equal to 30 mL/min)
• Solitary kidney
• Karnofsky Performance Status \< 80%
• Age greater than or equal to 18 years of age; UC is not a common cancer in children and without proven benefit, this combination of chemotherapy agents presents too great a risk for conducting as a phase I study in children.
• Karnofsky Performance Status greater than or equal to 60%
• Required Initial Laboratory Values:
• Absolute neutrophil count greater than or equal to 1.2 x 10(9)/L

You may not qualify if:

• For urothelial cancer patients, no prior combination systemic chemotherapy for metastatic disease, except:
• Single-agent radiosensitizing chemotherapy is not considered prior systemic therapy
• Prior neoadjuvant or adjuvant systemic chemotherapy (including cisplatin-based) is allowed provided it was completed greater than or equal to 6 months prior to the diagnosis of metastatic disease
• Prior intravesical therapy is permitted
• For non-urothelial cancer patients, no more than 1 prior line of combination systemic chemotherapy for metastatic disease is allowed
• Less than or equal to 2 weeks since radiation therapy
• Unstable angina
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction within 6 months
• History of stroke within 6 months
• Clinically significant peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy. Patients that are on anticoagulation therapy for DVT will be allowed to enroll and continue on the treatment dose of enoxaparin or other anticoagulation such a warfarin.
• Patients with contraindications to anticoagulation therapy for deep venous thrombosis such as:
• Patients on full treatment dose of anticoagulation such as those patients being treated for a deep vein thrombosis or pulmonary embolus.
• Presence of central nervous system or brain metastases

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Dredge K, Horsfall R, Robinson SP, Zhang LH, Lu L, Tang Y, Shirley MA, Muller G, Schafer P, Stirling D, Dalgleish AG, Bartlett JB. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res. 2005 Jan;69(1-2):56-63. doi: 10.1016/j.mvr.2005.01.002.

  PMID: 15797261 BACKGROUND

• Corral LG, Haslett PA, Muller GW, Chen R, Wong LM, Ocampo CJ, Patterson RT, Stirling DI, Kaplan G. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol. 1999 Jul 1;163(1):380-6.

  PMID: 10384139 BACKGROUND

• Schafer PH, Gandhi AK, Loveland MA, Chen RS, Man HW, Schnetkamp PP, Wolbring G, Govinda S, Corral LG, Payvandi F, Muller GW, Stirling DI. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003 Jun;305(3):1222-32. doi: 10.1124/jpet.102.048496. Epub 2003 Mar 20.

  PMID: 12649301 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Urethral Neoplasms; Urinary Bladder Neoplasms; Ureteral Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Gemcitabine; Carboplatin; Lenalidomide

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urethral Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Ureteral Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2011
• First Posted: May 12, 2011
• Study Start: September 26, 2011
• Primary Completion: February 7, 2017
• Study Completion: July 6, 2018
• Last Updated: April 14, 2026

Record last verified: 2025-09-15

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI

Locations

US (1)