Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urethral Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urethral Diseases

Urologic Diseases

Male Urogenital Diseases

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Carboplatin

Lenalidomide

Antimetabolites

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Standard of Care plus escalating doses of Lenalidomide

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

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

Andrea B Apolo, M.D.

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.

BACKGROUND:

* Gemcitabine plus carboplatin is an accepted first-line therapy in patients unfit for cisplatin chemotherapy with metastatic urothelial carcinoma or other solid tumor malignancies.
* Both non-clinical and clinical data support targeting angiogenesis in urothelial carcinoma and other solid tumors.
* Both non-clinical and clinical data support targeting the immune system in urothelial carcinoma and other solid tumors.
* Lenalidomide has both anti-angiogenic and potent immunomodulatory properties.
* Lenalidomide has been safely coadministered with cytotoxic therapy in patients with solid tumors and non-clinical studies demonstrate possible synergy with gemcitabine.

OBJECTIVES:

Primary

- To establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of lenalidomide which can be safely combined with gemcitabine and carboplatin in patients with advanced/metastatic UC and other solid tumors that are unfit for cisplatin.

Secondary

* To preliminarily evaluate the progression free survival, response rate and overall survival in patients with advanced/metastatic UC and other solid tumors treated with the combination of lenalidomide, gemcitabine, and carboplatin.
* To determine the effects of treatment on a set of 4 laboratory parameters (including Treg, sIL-2R, VEGF and CTC.) in the expansion cohort of patients with bladder cancer treated at the MTD.

ELIGIBILITY:

* Adult patients with histologic documentation of an advanced solid tumor with 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%
* No prior combination systemic chemotherapy for metastatic disease allowed for patients with UC, except single agent radiosensitizing chemotherapy (not considered prior systemic therapy), or prior neoadjuvant or adjuvant systemic chemotherapy (including cisplatin-based) is allowed provided if it was completed (Bullet) 6 months prior to diagnosis of metastatic disease; or prior intravesical therapy is permitted. Up to 1 line of chemotherapy in the metastatic setting is permitted for non UC patients.
* Laboratory evaluation must meet safety requirements, including a creatinine clearance greater than 30 using the Cockroft-Gault formula; may not be pregnant or breast-feeding.

DESIGN:

* This is a single-institution phase I study of gemcitabine (1000 mg/m2 on days 1 and 8) and carboplatin (AUC 5 on day 1) plus escalating doses of lenalidomide (GCL) in patients with advanced/metastatic UC and other solid tumors ineligible for cisplatin therapy. Lenalidomide will be administered once daily on days 1 through 14 every 21 days at escalating dose. An expansion cohort at the MTD of an additional 15 patients with bladder cancer will be enrolled in order to determine whether there are differences between pre-treatment and post-treatment levels of the following parameters: Treg, sIL- 2R, VEGF and CTC.
* Patients will receive a total of 6 cycles of gemcitabine and carboplatin in combination with lenalidomide unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles will be eligible to continue lenalidomide alone at the same dose and schedule until disease progression. Restaging evaluations will occur after every 3 cycles of treatment (approximately 9 weeks).
* Based on a standard 3+3 design with 4 dose levels per cohort, a maximum of 24 patients, with the potential for an additional 3 patients with CrCl\>60 mL/min, may need to be evaluated to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of lenalidomide in this combination therapy. With an expansion cohort of 15 patients at MTD, a total of 42 subjects may be enrolled over 1.5 -3 years.

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

A Phase I Study of Gemcitabine, Carboplatin and Lenalidomide (GCL) for Treatment of Patients With Advanced/Metastatic Urothelial Carcinoma (UC) and Other Solid Tumors

.All IPD recorded in the medical record will be shared with intramural investigators upon request

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

Percentage of patients whose cancer shrinks or disappears after treatment

time during which a patient shows no signs or symptoms of the growth or the spreading of a tumor

The length of time from the start of treatment that patients are still alive

determine the effects of treatment on a set of 5 laboratory parameters (including Treg, sIL-2R, VEGF, CTC and CEC in the expansion cohort of patients with bladder cancer treated at the MTD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Gemcitabine, Carboplatin, and Lenalidomide for Treatment of Advanced/Metastatic Urothelial Cancer and Other Solid Tumors	NCT01352962	Urethral Neopla... Neoplasms, Uret... Cancer of the U... Urethral Cancer	Gemcitabine Carboplatin Lenalidomide	18 Years -	National Institutes of Health Clinical Center (CC)
Gemcitabine, Carboplatin, and Lenalidomide for Treatment of Advanced/Metastatic Urothelial Cancer and Other Solid Tumors	NCT01352962	Urethral Neopla... Neoplasms, Uret... Cancer of the U... Urethral Cancer	Gemcitabine Carboplatin Lenalidomide	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for cancer of the urethra