Phase II Clinical Trial of Gemcitabine and Doxil® for Metastatic Renal Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the hypothesis that the combination of gemcitabine and doxil will have clinical activity in patients with metastatic renal cell carcinoma.

Detailed Description
-----------------
Patients with metastatic renal cell carcinoma who have received prior therapy with sorafenib, sunitinib or temsirolimus and have progressive disease may participate in this study if all eligibility criteria are met. Doxil will be administered on day 1 and gemcitabine on day 1 and 8 of a 21 day cycle. Tumor responses will be evaluated by RECIST. Up to six cycles of study treatment may be administered. Cardiac ejection fraction will be monitored.

Official Title
-----------------
Phase II Clinical Trial of Gemcitabine and Doxil® for Metastatic Renal Cell Carcinoma

Conditions
-----------------
Metastatic Renal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Gemcitabine
* Drug: Doxil


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with renal cell carcinoma who have had disease progression through sorafenib, sunitinib, or temsirolimus (within 6 months of treatment). Diagnosis of RCC has been confirmed by pathological or cytological examination of tissue obtained from the primary tumor or a metastatic site. Clear cell and non-clear cell histological variants are permitted. With the exception of prior gemcitabine or any anthracycline (e.g., doxorubicin, epirubicin, DOXIL), any number of prior therapies with are permitted. Prior nephrectomy is permitted but not required for eligibility. Patients who have received palliative radiation therapy (XRT) to any area other than the brain (see below) may begin therapy immediately after completion of XRT as long as the irradiated lesion(s) is/are not used for clinical response assessment. Brain metastases: Patients requiring XRT or gamma-knife (or similar) therapy to the brain must wait at least 4 weeks after the completion of irradiation before starting therapy. Only patients with either stable or regressing brain metastases after irradiation, as determined by CT or MRI, are eligible for therapy. No systemic therapy within 28 days prior to enrollment except as below: No sorafenib, sunitinib, temsirolimus therapy within 14 days prior to enrollment. Toxicities from prior therapy must have resolved to ≤Grade I. Survival: anticipated survival of at least three months. Renal function: creatinine ≥ 2.0 mg/dL. Patients must have a MUGA scan or 2-D echocardiogram indicating an ejection fraction of ≥50% within 42 days prior to the first dose of study drug. The method used at baseline must be used for later monitoring. Prior to each new cycle of therapy: hepatic function: AST, ALT ≥ 3X the upper limit of normal, unless the liver is involved by tumor, in which case the transaminases must be ≥ 5X the upper limit of normal. Total bilirubin must be ≥ 1.5 mg/dL. Prior to each new cycle of therapy: bone marrow function: absolute neutrophil count (ANC) ≥ 1,500; platelet count ≥ 100,000; hemoglobin ≥ 10 g/dL. Performance status: ECOG 0 or 1. Age: ≥ 18 years. Signed informed consent must be obtained from participating individuals. Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide, or surgical sterilization) during treatment and for three months after completing treatment. If a patient becomes pregnant while on study, the patient will be removed from the study and all drug treatment discontinued. Exclusion Criteria: Patients who have received prior therapy with gemcitabine or an anthracycline drug (e.g., doxorubicin, epirubicin, DOXIL). Patients with untreated central nervous system metastases. Patients with active bacterial or fungal infections. Patients with psychiatric disorders that would interfere with consent, compliance with protocol requirements, or follow-up. Patients with a history of prior malignancy other than RCC, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years. Patients with any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for the entry into the study. Pregnant or lactating women. History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the component of DOXIL, History of cardiac disease with New York Heart Association Class II or greater cardiac function or clinical evidence of congestive heart failure.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients will receive 3 cycles of therapy as an outpatient. Each 21-day cycle of therapy will comprise: Gemcitabine: IV on days 1 and 8. Doxil: on day 1. Patients with either responding or stable disease will continue to receive additional 3 cycles of therapy with gemcitabine and Doxil until there is radiological evidence of disease progression or they are unable or unwilling to continue treatment. | Drug: Gemcitabine<br>* 800 mg IV day 1 and 8<br>* Other names: Gemzar;Drug: Doxil<br>* 24 mg/m2 every 21 days IV<br>* Other names: adriamycin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Number of participants that experienced response/total number of participants per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan. Response was defined as Complete Response (CR), the disappearance of all target lesions; Partial Response (PR), a 30% or greater decrease in the sum of the longest diameter of target lesions. | Up to 18 weeks for individual; Up to 40 months for cohort | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Up to 40 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Doxil, Renal cell carcinoma, Kidney Cancer, Gemcitabine, Chemotherapy