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

This is an interventional treatment trial for Urethral Neoplasms focused on measuring 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 Read More

• INCLUSION CRITERIA:

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.

OR

-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
• Platelets greater than or equal to 100 x 10(9)/L
• Bilirubin less than or equal to 1.5 times the upper limit of normal for the institution or less than or equal to 3 mg/dl in a subject with Gilbert Syndrome
• Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 3 times the ULN for the institution (less than or equal to 5 times the ULN is acceptable if liver has tumor involvement).
• Serum creatinine < 2 or calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min
• Ability to understand and willingness to sign the written informed consent document.
• Patients must be able to swallow whole capsules. Capsules must not be crushed or chewed; capsules must not be opened.

EXCLUSION CRITERIA:

• 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
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1
• Anticipation of need for major surgical procedure during the course of the study

Those patients that develop DVTs during the study will be treated with anticoagulants and in certain cases, will continue on the protocol.

• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide. Further, they must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP, even if they have had a successful vasectomy. A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
• Inability to comply with study and/or follow-up procedures
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide, gemcitabine or carboplatin, or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Due to the possibility of infection reactivation, patients who are known seropositive for or who have active viral infection with human immunodeficiency virus (HIV) are NOT eligible.

INCLUSION OF WOMEN AND MINORITIES:

Both men and women of all races and ethnic groups are eligible for this trial.