Pemetrexed Plus Gemcitabine in Renal Cell Cancer
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma, Renal Cell
Intervention: Pemetrexed; Gemcitabine
Intervention description: 500 mg/m^2 IV Over 10 Minutes on Day 1.; 1500 mg/m^2 IV Over 30 Minutes on Day 1, Immediately After Infusion of Pemetrexed.
Intervention MeSH terms: Gemcitabine; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Healthy volunteers: No
Keywords: Renal Cell Carcinoma; Non-Clear Cell; Pemetrexed; Gemcitabine; LY231514; Alimta; MTA; Multitargeted Antifolate; NSC-698037; Gemcitabine Hydrochloride; Gemzar; RCC

Summary:

      Primary Objective:

        -  To determine the clinical activity of Pemetrexed + Gemcitabine in non-clear cell renal
           cell cancer (RCC). Clinical activity will take into account response rate and
           progression free survival (PFS).

      Secondary Objectives:

        -  To determine the toxicity of Pemetrexed + Gemcitabine in non-clear cell RCC.

        -  To estimate the survival rate of patients with non-clear cell RCC treated with this
           combination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed advanced non-clear cell
             RCC. Patients with locally recurrent disease are eligible. Patients with locally
             advanced unresectable RCC should have measurable metastatic disease to be eligible for
             the protocol. Patients with bilateral renal cancer are eligible as long as both
             cancers are of non-clear cell type and patients have metastatic disease.

          -  Patients must have measurable disease.

          -  Patients with previously treated or untreated, non-threatening brain metastasis are
             eligible. For previously treated patients, prior whole brain radiation therapy or
             stereotactic radiosurgery must be > 3 months from initiation of current therapy and
             there can be no plans for concurrent radiation while on this study. Patients who had
             surgical resection for brain metastasis are eligible to enroll after they recover from
             surgery.

          -  Life expectancy > 8 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Patients must have adequate organ and marrow function as defined below: (1) Hemoglobin
             >/= 9g/dl; (2) absolute neutrophil count >/= 1,500/microL; (3) platelets
             >/=100,000/microL; (4) total bilirubin </= 1.5 mg/dl; (5) aspartate aminotransferase
             (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) (SGPT) </= 2.5 *
             institutional upper limits of normal (uln), or </= 5 * uln if liver metastasis exists;
             (6) creatinine clearance (calculated by the Cockcroft-Gault formula) >/= 45 mL/min

          -  Patients must have recovered from any effects of surgery and/or radiation therapy and
             be free of significant detectable infection.

          -  Female patients of childbearing potential must have a normal plasma beta human
             chorionic gonadotropin (bHCG) within 24 hours prior to enrolling in the study.
             Patients with an elevated bHCG will undergo appropriate evaluation to rule out
             pregnancy (ie referral to OB-Gyn service, ultrasound) and if pregnancy is ruled out
             and elevated bHCG is determined to be of tumor origin, patients will be permitted to
             proceed on study.

          -  Patients of child fathering or childbearing potential must agree to practice a form of
             medically acceptable birth control while on study

          -  Patients must give written consent prior to initiation of therapy, in keeping with the
             policies of the institution. Patients with a history of major psychiatric illness must
             be judged able to fully understand the investigational nature of the study and the
             risks associated with the therapy. The only approved consent is attached to this
             protocol.

        Exclusion Criteria:

          -  Pregnant or lactating women.

          -  No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma
             of any site, or other cancers for which the patient has been adequately treated and
             disease free for 2 years.

          -  Patients must not have received more than 2 prior systemic therapies for RCC, but
             patients should not have received any prior chemotherapy for RCC. Chemotherapy given
             for other types of cancer more than 2 years prior to enrollment on this protocol is
             permitted.

          -  Patients must not be scheduled to receive any experimental drug for MRCC while on
             study. Patients are permitted to be on concomitant bisphosphonates or megestrol
             acetate. Patients are permitted to receive hematopoietic growth factors according to
             American Society of Clinical Oncology (ASCO) guidelines.

          -  Patients must not have had prior radiotherapy to areas of measurable disease, unless
             they have clearly progressive disease in this site, or there is measurable disease
             outside the area of prior radiation. Radiotherapy, if needed for palliation, must have
             been completed prior to enrollment on this study.

          -  Patients must not have any significant medical disease (other than the malignancy)
             that, in the opinion of the investigator, would significantly increase the risk for
             participation in this trial. Examples of exclusion: unstable angina pectoris, New York
             Heart Association (NYHA) Grade II or greater congestive heart failure, unstable
             symptomatic cardiac arrhythmias requiring medication (subjects with controlled chronic
             atrial fibrillation are eligible), myocardial infarction within the last 6 months,
             uncontrolled hypertension (blood pressure >160/110 on therapy) or uncontrolled
             diabetes mellitus.

          -  Patients must not have history of other diseases, metabolic dysfunction, physical
             examination finding, or clinical laboratory finding giving reasonable suspicion of a
             disease or condition that contraindicates the use of an investigational drug or that
             might affect the interpretation of the results of the study or render the subject at
             high risk from treatment complications.

          -  Patients unwilling to participate or unable to comply with the protocol for the
             duration of the study.

          -  Inability or unwillingness to take corticosteroid, folic acid or vitamin B12
             supplementation.

          -  Inability to interrupt aspirin or other non-steroidal anti-inflammatory agents for a 5
             day period (for short acting NSAIDs) or 8-day period (for long-lasting NSAIDs, such as
             piroxicam)