Clinical Trials Logo

Clinical Trial Summary

This is an open labeled phase I dose escalation study of hydroxychloroquine (HCQ) and RAD001 in patients with advanced renal cell carcinoma followed by a Phase II trial of RAD001 with HCQ. The target population are patients with one to three prior treatments for advanced renal cell carcinoma. In the phase I portion a traditional 3+3 design will be used to determine the maximal tolerated dose and/or recommended phase II dose for HCQ in combination with RAD001 po 10 mg/day.


Clinical Trial Description

This protocol describes a multicenter phase I/II trial of RAD001 in combination with hydroxychloroquine (HCQ) (phase I anticipated n=6-12) with a 35 patient phase II trial in patients with previously treated (1-3 prior regimens) advanced renal cell carcinoma. The preclinical rationale for this combination is extensive, the safety of HCQ combination strategies has been established, and effective autophagy pharmacodynamics (PD), and pharmacokinetics (PK) assays are available to guide development. The practical advantage of combination with HCQ is that this drug is off patent, commercially available, and is investigational new drug (IND) exempt. The institutions involved have combined 11 clinical protocols open for accrual involving HCQ, so regulatory approval will be rapid. There are no competing HCQ protocols for advanced renal cell carcinoma. As described in the sample size justification we are setting a high threshold to consider RAD001 + HCQ active since there are many competitors and other potential rational combinations. The 35 patient sample size is designed as a 2 stage phase II trial that will guide the go/no-go decision regarding the conduct of a followup randomized study to definitively prove efficacy. The primary (6 month PFS) and secondary outcomes (response rate, toxicity rates, correlative endpoints) will be analyzed for the entire group, and for patient populations stratified by number of prior therapies. The phase I portion of this trial is anticipated to be short, based on our experience from other HCQ trials. As a safety measure we have included intermediate dose levels which will only be used if there are Dose Limiting Toxicities (DLTs). Since we have seen responses at lower doses of HCQ in other trials, and because frequently over months HCQ dose is lowered from Maximum Tolerated Dose (MTD) doses in many trials because of nausea and anorexia, we would like to have some data on renal cell patients treated at the lower dose levels. If there is activity demonstrated at lower doses, this would be informative for dose modification decisions in patients treated on the dose expansion. The patient population for this trial, including the phase I dose escalation portion is advanced renal cell carcinoma with 1-3 prior treatments. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01510119
Study type Interventional
Source Abramson Cancer Center of the University of Pennsylvania
Contact
Status Completed
Phase Phase 1/Phase 2
Start date September 2011
Completion date January 5, 2017

See also
  Status Clinical Trial Phase
Completed NCT01896271 - High Dose IL-2 and Stereotactic Ablative Body Radiation Therapy for Metastatic Renal Cancer Phase 2
Recruiting NCT06059014 - Phase I/II Study Evaluating PSMA Targeted Radionuclide Therapy in Adult Patients With Metastatic Clear Cell Renal Cancer Phase 1/Phase 2
Active, not recruiting NCT05122546 - CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer Phase 1
Active, not recruiting NCT04904302 - Sitravatinib and Nivolumab for the Treatment of Metastatic or Advanced Clear Cell Renal Cell Cancer Phase 2
Recruiting NCT04510597 - Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial Phase 3
Terminated NCT02781506 - Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma Phase 2
Recruiting NCT06399419 - CBM588 Capsules in Combination With Nivolumab and Ipilimumab for the Treatment of Advanced Stage Kidney Cancer Phase 1
Not yet recruiting NCT06361810 - PSMA Therapy and Immunotherapy in Kidney Cancer Phase 1/Phase 2
Recruiting NCT06428708 - [18F] PSMA-1007 PET/CT in Metastatic Clear Cell Renal Cell Carcinoma Early Phase 1
Recruiting NCT04370509 - Pembrolizumab With or Without Axitinib for Treatment of Locally Advanced or Metastatic Clear Cell Kidney Cancer in Patients Undergoing Surgery Phase 2
Recruiting NCT05012371 - Lenvatinib With Everolimus Versus Cabozantinib for Second-Line or Third-Line Treatment of Metastatic Renal Cell Cancer Phase 2
Terminated NCT03334409 - Pazopanib Hydrochloride With or Without Ascorbic Acid in Treating Patients With Kidney Cancer That Is Metastatic or Cannot Be Removed by Surgery Phase 2
Completed NCT02848768 - Validation of a Predictive Nomogram of Response or Resistance to Targeted Therapies in Metastatic Clear Cell Renal Cell Carcinoma N/A
Recruiting NCT05361720 - Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study Phase 2
Terminated NCT03260504 - Aldesleukin and Pembrolizumab in Treating Patients With Advanced or Metastatic Kidney Cancer Phase 1
Terminated NCT01391130 - A Study of LY2510924 and Sunitinib in Patients With Metastatic Renal Cell Carcinoma Phase 2
Completed NCT02002312 - Phase II Study of Lutetium-177 Labeled Girentuximab in Patients With Advanced Renal Cancer Phase 2
Recruiting NCT04388852 - DS3201 and Ipilimumab for the Treatment of Metastatic Prostate, Urothelial and Renal Cell Cancers Phase 1
Recruiting NCT05879471 - 68Ga-NY104 PET/CT in Patients With Metastatic Clear Cell Renal Cell Carcinoma Phase 2
Recruiting NCT06349642 - Predicting Response to Immune Checkpoint Inhibitors Across Solid Tumors Using a Live Tumor Diagnostic Platform