Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory/Ineligible, Advanced, Squamous Cell Carcinoma

July 14, 2015 updated by: New Mexico Cancer Care Alliance

A Phase II Study of Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory or -Ineligible, Advanced, Squamous Cell Carcinoma of the Head and Neck

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center @ Lovelace Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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.

  2. 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

  3. 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

  4. Measurable disease based on response evaluation criteria in solid tumors (RECIST)

    - disease in previously irradiated sites is considered measurable if there has been unequivocal progression of the lesion after radiotherapy, or the lesion contains residual carcinoma by biopsy more than 6 weeks after completion of radiotherapy

  5. Easter Cooperative Oncology Group (ECOG) performance status 0-2 at time of informed consent

  6. Adequate hematologic reserve and organ function

    • Absolute neutrophil count > 1200/µl
    • Platelet count > 100,000/µl
    • Renal function: Serum Creatinine ≤ 1.5x upper limit of normal (ULN)
    • Liver function: Total bilirubin ≤ 1.5x ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN
  7. Able to provide written, voluntary consent
  8. Patients with reproductive potential must use an effective contraceptive method.
  9. Male or female, age ≥ 18 years
  10. Life expectancy ≥ 12 weeks

Exclusion Criteria:

  1. Nasopharyngeal primary site, if WHO grade II or III
  2. Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced disease setting
  3. Prior treatment blocking EGFR in the curative-intent setting, if delivered in the previous 6 months
  4. Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR)
  5. Sensitivity to temsirolimus or erlotinib
  6. Uncontrolled metastatic disease of the central nervous system
  7. Radiotherapy within the 2 weeks before Cycle 1' Day 1
  8. Surgery within the 2 weeks before Cycle 1' Day 1
  9. Pregnant or lactating females
  10. Myocardial infarction or ischemia within the 6 months preceding study treatment
  11. Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications
  12. No other concurrent, investigational anti-neoplastic agent will be permitted
  13. History of prior malignancy within the prior five years, with the exception of non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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
Drug: Erlotinib
Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.
Other Names:
  • Tarceva
  • OSI-774
Drug: Temsirolimus
In the absence of Grade 3 or higher toxicity, a single, intra-patient dose increase of temsirolims to 20 mg intravenously weekly is permitted after the first 28 day cycle. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.
Other Names:
  • Torisel
  • CCI-779

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity Profile
Time Frame: 3 years
Toxicities (i.e. Adverse Events) are evaluated prior to each treatment and during any clinical visit. Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The number of patients affected by adverse events of grade 3 or higher will be reported.
3 years
Overall Response Rate (ORR)
Time Frame: 3 years
Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI:) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall response rate (ORR) is the sum of the percentages of patients achieving complete and partial responses
3 years
Overall Survival (OS)
Time Frame: 3 years
The time from treatment initiation to death by any cause
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New Mexico Cancer Care Alliance

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Homan Fekrazad, MD, University of New Mexico Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (ACTUAL)

September 1, 2012

Study Completion (ACTUAL)

December 1, 2012

Study Registration Dates

First Submitted

November 5, 2009

First Submitted That Met QC Criteria

November 5, 2009

First Posted (ESTIMATE)

November 6, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

August 10, 2015

Last Update Submitted That Met QC Criteria

July 14, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INST OSI4641s
  • OSI4641s (OTHER: Genentech, Inc)
  • NCI-2011-02948 (REGISTRY: NCI Clinical Trials Reporting Program)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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