Study of Hydroxychloroquine and Aldesleukin in Renal Cell Carcinoma Patients (RCC)
The main goal of the research study is to determine whether treating renal cell cancer patients with the study drug, hydroxychloroquine, along with IL-2, a standard treatment of kidney cancer that has spread to other parts of the body, can make the cancer easier to kill and eliminate. Another goal is to see how the study drug affects the body's immune cells which fight cancer cells.
Metastatic Renal Cell Carcinoma
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Inhibiting the Systemic Autophagic Syndrome - A Phase I/II Study of Hydroxychloroquine and Aldesleukin in Renal Cell Carcinoma Patients (RCC). A Cytokine Working Group (CWG) Study|
- Proportion of patients with metastatic RCC treated with IL-2 + HCQ at 1200mg/d who experience a clinical complete response. [ Time Frame: up to 3 years to accrue and assess outcome ] [ Designated as safety issue: No ]
Evaluation of target lesions:
-Complete Response (CR): Disappearance of all target lesions
Evaluation of non-target lesions
-Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level
- Complete response (CR), overall survival (OS) and time to progression (TTP) of patients with metastatic RCC treated with IL-2 + HCQ to the historical data of patients treated with high dose IL-2 alone in the CWG data base. [ Time Frame: up to 3 years to accrue and assess outcome ] [ Designated as safety issue: No ]
CR (target lesions): Disappearance of all target lesions CR (non-target lesions): Disappearance of all non-target lesions and normalization of tumor marker level
Survival: date of first protocol treatment to the date of death, or censored at date of last contact.
TTP: time from the date of first protocol treatment until the date disease progression criteria are met (in responding patients progression criteria uses the reference of the smallest measurements recorded since the treatment started) or is censored at date of last disease assessment for those who have not progressed.
- Safety/toxicity of IL-2 + HCQ compared to CWG database of metastatic RCC patients treated with IL-2 alone: # doses IL-2 during 1st course; toxicity after scheduled 9th dose IL-2; frequency grade III and IV or unexpected or rare toxicities [ Time Frame: up to 3 years to accrue and assess outcome ] [ Designated as safety issue: Yes ]Number of doses of IL-2 administered during the first course of therapy; toxicity after the scheduled 9th dose of IL-2; frequency of grade III and IV or unexpected or rare toxicities
- Baseline laboratory parameters outlined under "description" (to be correlated with toxicity, response, and survival). [ Time Frame: up to 3 years to accrue and assess outcome ] [ Designated as safety issue: Yes ]Baseline laboratory parameters include: miRNAs pre- and post-IL-2; KIR genotyping; T and NK cell enumeration and activation in the peripheral blood; circulating mDC and pDC frequency and DC function, TCR-zeta chain expression in T and NK cells, arginase or arginine levels; circulating cytokines, chemokines, growth factors and angiogenesis mediators
- Known prognostic criteria for RCC patients (Motzer criteria, performance status, prior nephrectomy, presence of liver and/or bone metastases categories) on clinical outcome. [ Time Frame: up to 3 years to accrue and assess outcome ] [ Designated as safety issue: No ]
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: Hydroxychloroquine + IL-2
One course of treatment (84 days) will consist of high dose (600,000 IU/kg) bolus IL-2 administered intravenously every 8 hours on days 1-5 and 15-19 (maximum 14 doses/5 days of administration) and hydroxychloroquine (HCQ) orally started two weeks prior to IL-2 infusions and continued while able to take oral medication for up to 3 courses.
Continuous oral administration (at 600 mg/d or 1200 mg/d) will be initiated prior to the first dose (day -14) given 14 days prior to initiation of the first dose of IL-2 and then daily or twice a day throughout all three treatment courses.
Other Name: PlaquenilDrug: IL-2
600,000 IU/kg IV bolus q 8 hrs x days 1-5 and 15-19 (maximum 28 doses - 14 per 5 day cycle) of each 84-day course
Other Name: Aldesleukin
The rationale for combining the high dose bolus aldesleukin with hydroxychloroquine includes potential positive interactions on the immune regulatory side, non-overlapping toxicities, and potential for prolongation and increased number of responses based on murine studies conducted at the University of Pittsburgh. This study is a multi-center phase II study designed to estimate the efficacy of combination therapy of standard high dose bolus IL-2 and various doses of hydroxychloroquine therapy in metastatic RCC patients.
|Contact: Michael T. Lotze, MDfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute/UPMC Cancer Centers||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15221|
|Contact: Michael T. Lotze, MD 412-623-6790 email@example.com|
|Principal Investigator:||Michael T. Lotze, MD||University of Pittsburgh|