Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

Study Overview
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Brief Summary
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The purpose of this study is to find out the good and bad effects that occur when temsirolimus is added to standard chemotherapy with carboplatin and paclitaxel.

Official Title
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A Phase I/II Study of Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

Conditions
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Squamous Cell Cancer, Head and Neck Cancer

Intervention / Treatment
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* Drug: Temsirolimus + Weekly Paclitaxel + Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have microscopically confirmed head and neck squamous cell carcinoma (HNSCC), recurrent and/or metastatic. Confirmation of HNSCC may be obtained from the primary site or metastatic disease. Patients must be at least 18 years of age. Karnofsky Performance status must be ≥ 70%. Disease must be measurable by RECIST criteria. At least 6 weeks must have elapsed from previous radiation therapy. Patient must have recovered from the acute toxic effects of treatment prior to study enrollment. Adequate organ function, as follows: Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥ 100 X 109/L, and hemoglobin ≥ 9 g/dL. Hepatic: total bilirubin within normal limits (≤ 1.0 mg/dL); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 X ULN (upper limit of normal) Renal: Serum creatinine ≤ 1.3 mg/dL. Patients with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) ≥ 45 mL/min based on the standard Cockroft and Gault formula. Patients of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Patients must agree to use a reliable method of birth control during and for 3 months following the last dose of study drug. Patients must sign an informed consent document. Exclusion Criteria: Previous exposure to temsirolimus or other mTOR inhibitors More than 2 prior cytotoxic regimens in the recurrent/metastatic disease setting History of any brain metastases Patients who require concomitant medications that are metabolized by hepatic CYP3A4, due to potential drug-drug interaction with temsirolimus Patients with known active interstitial pneumonitis Active infection or serious underlying medical condition that would impair the patient's ability to receive protocol treatment. Women who are pregnant or lactating Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis Diagnosis of Nasopharyngeal cancer is excluded. Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living) Therapeutic anticoagulation with Coumadin (warfarin) Hypertriglyceridemia ≥ grade 2 (CTCAE version 3.0). Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry. If O2 saturation is ≤ 88% at rest, further pulmonary function tests (PFTs) should be ordered to confirm normal pulmonary function and eligibility.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temsirolimus + Weekly Paclitaxel + Carboplatin<br>In Part 1 (Phase I) of the study, the primary endpoint is to establish the phase II recommended dose for the combination of temsirolimus + weekly paclitaxel + carboplatinPart 1 (Phase I) features a standard 3 + 3 phase I dose escalation design. Up to 3 dose levels are planned in the Phase I portion of the study. In Part 2 (Phase II) of the study, the primary endpoint is to determine the objective response rate (CR or PR) after two cycles (approximately 6 weeks) of treatment with the combination of temsirolimus + weekly paclitaxel + carboplatin as palliative therapy for recurrent or metastatic HNSCC. A two-stage design will be employed. | Drug: Temsirolimus + Weekly Paclitaxel + Carboplatin<br>* Temsirolimus Per dose escalation scheme Level 1 (15 mg) 2 (20 mg) Level 3 (25 mg) IVPB 30 minutes weekly (3 weeks on, 1 week off) days 1 and 8. Paclitaxel 80 mg/m2 IVPB 1 hour weekly (2 weeks on, 1 week off) days 1 and 8. Carboplatin AUC 1.5 IVPB 30 minutes days 1 and 8. On Day 15 of each cycle, patients begin the rest week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II Recommended Dose for the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin. |  | 2 years | 
| To Determine the Objective Response Rate (CR or PR) After Two Cycles of Treatment With the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin as Palliative Therapy for Recurrent or Metastatic HNSCC | Evaluation of target lesions: Complete Response - disappearance of all target lesions Partial Response - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Progressive Disease - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, or the appearance of one of more new lesions Stable Disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Adverse Events | Safety will be assessed in terms of AEs according to CTCAE version 3.0 | 2 years | 
| Median Overall Survival |  | 2 years | 
| Number of Participants With Potential Molecular Markers of Resistance to mTOR Inhibition |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paclitaxel, Carboplatin, Temsirolimus, Head and Neck, recurrent and/or metastatic, 09-131