A Phase I Study of SUNITINIB and Rapamycin in Advanced Non-Small Cell Lung Cancer (NSCLC) (SU/Rapamycin)
To define the optimal dose of sunitinib when given in combination with rapamycin 2mg.
To determine the maximum tolerated dosage of sunitinib and rapamycin given in this fashion.
To determine the how many times and how severe other toxicities of this combination therapy.
To determine how quickly the patient(s) will respond the the drug, overall survival and time to progression for this combination therapy.
|Non-Small Cell Lung Cancer||Drug: sunitinib and rapamycin (Drug will be held)||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Study of SUNITINIB and Rapamycin in Advanced Non-Small Cell Lung Cancer (NSCLC)|
- To define the optimal dose of sunitinib when given in combination with rapamycin 2mg daily. [ Time Frame: 6 weeks ]
- Determine the dose limiting toxicity of sunitinib and rapamycin [ Time Frame: 6 weeks ]
- Incidence and severity of other toxicities [ Time Frame: 30 days after the end of treatment ]Cycles are 6 weeks long and can have as many as 9 cycles
- Response rates [ Time Frame: 30 days after end of treatment ]
- Overall survival [ Time Frame: 12 months from date of first treatment ]
|Study Start Date:||November 2007|
|Study Completion Date:||December 2012|
|Primary Completion Date:||February 2010 (Final data collection date for primary outcome measure)|
Patients will be instructed to take sunitinib and rapamycin every morning for 4 weeks, then to take 2 weeks off. The sunitinib dose will be 25mg in the first cohort and the rapamycin dose will be 2 mg.
Drug: sunitinib and rapamycin (Drug will be held)
Any toxicity causing a total of 14 days delay of therapy will be considered dose limiting.
We propose to conduct a phase I study of sunitinib and rapamycin administered daily for weeks 1-4)in a 6-week cycle. The rationale for this study includes:
- Sunitinib is a tyrosine kinase inhibitor that targets multiple receptor pathways critical for cell growth. It has both antiangiogenic and direct antitumor activities.
- Resistance to receptor tyrosine kinase inhibitors is well-documented. The mammalian target of rapamycin (mTOR) pathway may play a critical role in imatinib-refractory GIST. Rapamycin and other agents that inhibit mTOR demonstrate antiangiogenic and antitumor properties by decreasing VEGF production and decreasing responsiveness to VEGF.
- Sunitinib is approved and well-tolerated at doses as high as 75mg daily. The typical dose in most Phase II and III trials has been 50mg/day, given on a four weeks on/two weeks off schedule. There are, however, recent trials looking at a lower dosage, 37.5 mg, in NSCLC.
- Rapamycin at doses greater than 2 mg daily is documented to be well-tolerated in renal transplant patients. In renal transplant patients, 2mg daily is the typical starting dose. This dose was used in one of the phase I studies of rapamycin in glioblastoma.
- The administration of two oral medications, taken once daily, may be more convenient to patients than iv administration of chemotherapy at an infusion center every 1-3 weeks.
- Based on these data, initial dosing of sunitinib beginning at 37.5 mg orally everyday for 4 weeks, followed by 2 weeks off, in combination with rapamycin 2 mg/day orally for 6 weeks during a 6 week cycle should be well tolerated and allow for dose-finding escalation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00555256
|United States, Missouri|
|Washington University School of medicine|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Ramaswamy Govindan, M.D.||Washington University School of Medicine|