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

This study has been terminated.
(High patient withdrawal rate)
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier:
NCT01009203
First received: November 5, 2009
Last updated: July 14, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Squamous Cell Carcinoma
Drug: Erlotinib
Drug: Temsirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory or -Ineligible, Advanced, Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by New Mexico Cancer Care Alliance:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Toxicity Profile [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    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.

  • Overall Response Rate (ORR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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

  • Overall Survival (OS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The time from treatment initiation to death by any cause


Enrollment: 13
Study Start Date: December 2009
Study Completion Date: December 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01009203

Locations
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87106
University of New Mexico Cancer Center @ Lovelace Medical Center
Albuquerque, New Mexico, United States, 87102
Sponsors and Collaborators
New Mexico Cancer Care Alliance
Genentech, Inc.
Investigators
Principal Investigator: Homan Fekrazad, MD University of New Mexico Cancer Center
  More Information

Publications:
Responsible Party: New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier: NCT01009203     History of Changes
Other Study ID Numbers: INST OSI4641s, OSI4641s, NCI-2011-02948
Study First Received: November 5, 2009
Results First Received: June 15, 2015
Last Updated: July 14, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by New Mexico Cancer Care Alliance:
squamous cell carcinoma
head
neck
aerodigestive

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Erlotinib
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015