A Phase II Study of Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory or -Ineligible, Advanced, Squamous Cell Carcinoma of the Head and Neck
Overview
- Phase
- Phase 2
- Intervention
- Erlotinib
- Conditions
- Squamous Cell Carcinoma
- Sponsor
- New Mexico Cancer Care Alliance
- Enrollment
- 13
- Locations
- 2
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Terminated
- Last Updated
- 10 years ago
Overview
Brief Summary
The primary hypothesis of this study is that the addition of mammalian target of rapamycin (mTOR) blockade to conventional epidermal growth factor receptor (EGFR) blockade will result in synergistic clinical activity in Squamous Cell Carcinoma of the Head and Neck (SCCHN), consistent with preclinical xenograft data. Patients will be treated with the combination of temsirolimus and erlotinib, at the previously established Maximal Tolerated Dose (MTD). The primary signal of efficacy will be progression free survival (PFS), anticipating that PFS will be prolonged compared to historical PFS in SCCHN patients treated with erlotinib or cetuximab monotherapy.
Detailed Description
This is a phase II, multicenter, single arm, open-label study. Thirty-seven patients with advanced, platinum-refractory or platinum-ineligible squamous cell carcinoma of the head and neck will be sequentially enrolled to a single treatment arm. Patients will be treated with continuous, 28-day cycles of 150 mg of erlotinib by mouth daily and 15 mg of temsirolimus intervenously weekly. In the absence of grade 3 or higher toxicity in the first cycle, a single, intra-patient dose increase to 20 mg temsirolimus will be permitted.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, from any primary site. Nasopharyngeal carcinoma, World Health Organization (WHO) Grade I, will be included.
- •Advanced disease, fulfilling one of the criteria defined below:
- •Incurable disease as assessed by surgical or radiation oncology
- •Metastatic (M1) disease
- •Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity
- •Platinum-refractory or platinum-ineligible, fulfilling one of the criteria defined below:
- •disease progression during or after 4-6 cycles of platinum-containing therapy in the advanced setting
- •disease progression within 6 months of curative-intent treatment, which included platinum-based chemotherapy
- •ineligible for platinum-containing therapy, in the opinion of the medical oncologist, due to medical comorbidities or unacceptable risk for toxicity
- •patient refuses platinum-containing therapy
Exclusion Criteria
- •Nasopharyngeal primary site, if WHO grade II or III
- •Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced disease setting
- •Prior treatment blocking EGFR in the curative-intent setting, if delivered in the previous 6 months
- •Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR)
- •Sensitivity to temsirolimus or erlotinib
- •Uncontrolled metastatic disease of the central nervous system
- •Radiotherapy within the 2 weeks before Cycle 1' Day 1
- •Surgery within the 2 weeks before Cycle 1' Day 1
- •Pregnant or lactating females
- •Myocardial infarction or ischemia within the 6 months preceding study treatment
Arms & Interventions
Temsirolimus and Erlotinib
Erlotinib (Tarceva) at 150 mg by mouth daily + Temsirolimus (Torisel) at 15 mg intravenously weekly. Each cycle is comprised of 28 days
Intervention: Erlotinib
Temsirolimus and Erlotinib
Erlotinib (Tarceva) at 150 mg by mouth daily + Temsirolimus (Torisel) at 15 mg intravenously weekly. Each cycle is comprised of 28 days
Intervention: Temsirolimus
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: 3 years
The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or unequivocal progression of existing non-target lesion, the appearance of new lesions, death due to disease without prior objective documentation of progression, or global deterioration in health status attributable to disease requiring a change in therapy without objective evidence of progression.
Secondary Outcomes
- Toxicity Profile(3 years)
- Overall Response Rate (ORR)(3 years)
- Overall Survival (OS)(3 years)