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

• ClinicalTrials.gov Identifier: NCT01016769
• Recruitment Status: Completed
• First Posted: November 19, 2009
• Results First Posted: June 26, 2019
• Last Update Posted: June 26, 2019
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: NATL COMP CA NETWORK; Pfizer
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: November 18, 2009
• First Posted Date: November 19, 2009
• Results First Submitted Date: October 9, 2018
• Results First Posted Date: June 26, 2019
• Last Update Posted Date: June 26, 2019
• Actual Study Start Date: November 2009
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 3, 2019)

• 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 ]
  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

Original Primary Outcome Measures (submitted: November 18, 2009)

• 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: 8 weeks ]

Current Secondary Outcome Measures (submitted: June 3, 2019)

• Number of Participants Who Experienced Adverse Events [ Time Frame: 2 years ]
  Safety will be assessed in terms of AEs according to CTCAE version 3.0
• Median Overall Survival [ Time Frame: 2 years ]
• Number of Participants With Potential Molecular Markers of Resistance to mTOR Inhibition [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: November 18, 2009)

• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Squamous Cell Cancer
• Head and Neck Cancer

Intervention

Drug: 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.

Study Arms

Experimental: Temsirolimus + Weekly Paclitaxel + Carboplatin

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.

Intervention: Drug: Temsirolimus + Weekly Paclitaxel + Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 18, 2009): 48
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 2018
• Actual Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01016769
• Other Study ID Numbers: 09-131
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Memorial Sloan Kettering Cancer Center
• Study Sponsor: Memorial Sloan Kettering Cancer Center

Collaborators

• NATL COMP CA NETWORK
• Pfizer

Investigators

• Principal Investigator: David Pfister, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: June 2018