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

Primary Purpose

Squamous Cell Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Erlotinib
Temsirolimus
Sponsored by
New Mexico Cancer Care Alliance
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma focused on measuring squamous cell carcinoma, head, neck, aerodigestive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of New Mexico Cancer Center @ Lovelace Medical Center
  • University of New Mexico Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temsirolimus and Erlotinib

Arm Description

Erlotinib (Tarceva) at 150 mg by mouth daily + Temsirolimus (Torisel) at 15 mg intravenously weekly. Each cycle is comprised of 28 days

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
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
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)
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)
The time from treatment initiation to death by any cause

Full Information

First Posted
November 5, 2009
Last Updated
July 14, 2015
Sponsor
New Mexico Cancer Care Alliance
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01009203
Brief Title
Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory/Ineligible, Advanced, Squamous Cell Carcinoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Terminated
Why Stopped
High patient withdrawal rate
Study Start Date
December 2009 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New Mexico Cancer Care Alliance
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma
Keywords
squamous cell carcinoma, head, neck, aerodigestive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temsirolimus and Erlotinib
Arm Type
Experimental
Arm Description
Erlotinib (Tarceva) at 150 mg by mouth daily + Temsirolimus (Torisel) at 15 mg intravenously weekly. Each cycle is comprised of 28 days
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Other Intervention Name(s)
Tarceva, OSI-774
Intervention Description
Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.
Intervention Type
Drug
Intervention Name(s)
Temsirolimus
Other Intervention Name(s)
Torisel, CCI-779
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Toxicity Profile
Description
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.
Time Frame
3 years
Title
Overall Response Rate (ORR)
Description
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
Time Frame
3 years
Title
Overall Survival (OS)
Description
The time from treatment initiation to death by any cause
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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 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 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 Easter Cooperative Oncology Group (ECOG) performance status 0-2 at time of informed consent 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 Able to provide written, voluntary consent Patients with reproductive potential must use an effective contraceptive method. Male or female, age ≥ 18 years Life expectancy ≥ 12 weeks Exclusion Criteria: Nasopharyngeal primary site, if WHO grade II or III Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced disease setting Prior treatment blocking EGFR in the curative-intent setting, if delivered in the previous 6 months Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR) Sensitivity to temsirolimus or erlotinib Uncontrolled metastatic disease of the central nervous system Radiotherapy within the 2 weeks before Cycle 1' Day 1 Surgery within the 2 weeks before Cycle 1' Day 1 Pregnant or lactating females Myocardial infarction or ischemia within the 6 months preceding study treatment Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications No other concurrent, investigational anti-neoplastic agent will be permitted 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Homan Fekrazad, MD
Organizational Affiliation
University of New Mexico Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of New Mexico Cancer Center @ Lovelace Medical Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23384718
Citation
Bauman JE, Arias-Pulido H, Lee SJ, Fekrazad MH, Ozawa H, Fertig E, Howard J, Bishop J, Wang H, Olson GT, Spafford MJ, Jones DV, Chung CH. A phase II study of temsirolimus and erlotinib in patients with recurrent and/or metastatic, platinum-refractory head and neck squamous cell carcinoma. Oral Oncol. 2013 May;49(5):461-7. doi: 10.1016/j.oraloncology.2012.12.016. Epub 2013 Feb 4.
Results Reference
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Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory/Ineligible, Advanced, Squamous Cell Carcinoma

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