Clinical trial NCT01016769: Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)
Official title: A Phase I/II Study of Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Squamous Cell Cancer
Head and Neck Cancer
Keywords: Paclitaxel
Carboplatin
Temsirolimus
Head and Neck
recurrent and/or metastatic
09-131
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: NATL COMP CA NETWORK
name: Pfizer
First posted: 2009-11-19
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase II Recommended Dose for the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin.
timeFrame: 2 years
measure: 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
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of Participants Who Experienced Adverse Events
timeFrame: 2 years
measure: Median Overall Survival
timeFrame: 2 years
measure: Number of Participants With Potential Molecular Markers of Resistance to mTOR Inhibition
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center at Basking Ridge
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering at Mercy Medical Center
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: David Pfister, MD
role: PRINCIPAL_INVESTIGATOR
References: