Overview

This trial is active, not recruiting.

Conditions squamous cell cancer, head and neck cancer
Treatment temsirolimus + weekly paclitaxel + carboplatin
Phase phase 1/phase 2
Sponsor Memorial Sloan Kettering Cancer Center
Collaborator NATL COMP CA NETWORK
Start date November 2009
End date November 2017
Trial size 48 participants
Trial identifier NCT01016769, 09-131

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
temsirolimus + weekly paclitaxel + carboplatin
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.

Primary Outcomes

Measure
To establish the phase II recommended dose for the combination of temsirolimus + weekly paclitaxel + carboplatin.
time frame: 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
time frame: 6 weeks

Secondary Outcomes

Measure
To establish the safety of temsirolimus + weekly paclitaxel + carboplatin
time frame: 2 years
To estimate median overall survival
time frame: 2 years
To identify potential molecular markers of resistance to mTOR inhibition in tumor specimens obtained as part of routine clinical care
time frame: 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title A Phase I/II Study of Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)
Principal investigator David Pfister, MD
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center.