Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy (MAESTRO HN)

February 23, 2017 updated by: National Cancer Institute (NCI)

A T1 Translational Multicenter Randomized Phase II Study of Temsirolimus Versus Cetuximab Plus Temsirolimus in Patients With Recurrent / Metastatic Head and Neck Cancer, Who Failed Prior EGFR Based Therapy

This phase II trial studies how well giving temsirolimus together with cetuximab works compared to temsirolimus alone in treating patients with recurrent and/or metastatic head and neck cancer who did not respond to previous therapy. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving temsirolimus together with cetuximab is more effective than giving temsirolimus alone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Primary endpoint is progression free survival (PFS) of cetuximab/temsirolimus combination cohort (Arm A) compared to temsirolimus alone (Arm B).

SECONDARY OBJECTIVES:

I. Progression-free survival (PFS) of cetuximab/temsirolimus combination group (Arm A) and temsirolimus control group (Arm B) compared to a historic control cohort.

II. Subgroup analysis of myofibroblast (+) cohort (PFS). III. Overall survival (OS). IV. Toxicities. V. Response (Response Evaluation Criteria in Solid Tumors [RECIST])/absolute tumor shrinkage (waterfall plot analysis).

VI. Activity of combination therapy (temsirolimus/cetuximab) after failure (progressive disease [PD]) of temsirolimus monotherapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive temsirolimus intravenously (IV) over 30-60 minutes and cetuximab IV over 1-2 hours once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive temsirolimus as in Arm A. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may cross over to Arm A.

After completion of study therapy, patients are followed up for a minimum of 8 weeks and then once a year for 5 years.

Study Type

Interventional

Enrollment (Actual)

86

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

  • China
    • Hong Kong
      • Shatin, Hong Kong, China, OX1 3UJ
        • Chinese University of Hong Kong-Prince of Wales Hospital
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic in Arizona
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Mayo Clinic in Florida
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Harvey, Illinois, United States, 60426
        • Ingalls Memorial Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61615
        • Illinois CancerCare-Peoria
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Central Illinois Hematology Oncology Center
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Fort Wayne Medical Oncology and Hematology Inc-Parkview
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, United States, 21201
        • University of Maryland/Greenebaum Cancer Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro Minnesota Community Oncology Research Consortium
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Hospital and Clinics

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:

  • Histologically/cytologically confirmed diagnosis of squamous cell carcinoma of head and neck origin not amenable to curative intent therapy; information on prior exposure to cetuximab (duration, single agent/combined with chemotherapy/combined with radiation, best response, interval prior to study entry) will be collected
  • Progressive disease by RECIST criteria (or unequivocal clinical progression) on a cetuximab based therapy in any line of therapy for recurrent/metastatic disease; prior use of cetuximab for recurrent/metastatic disease is defined as palliative intent use either alone or in combination with chemotherapy with a minimum of 2 weeks of uninterrupted treatment with cetuximab; treatment with cetuximab during radiotherapy or chemoradiotherapy is not sufficient
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1
  • Presence of measurable lesions by RECIST: patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
  • Knowledge of the anatomic site of the original tumor (oropharynx versus non-oropharynx) or alternatively human papilloma virus (HPV) status; the trial will stratify patients by oropharynx versus non-oropharynx origin; HPV(+) tumors will be counted in the oropharynx cohort, HPV(-) tumors in the non-oropharynx cohort; at a later point all patients will undergo HPV testing as part of this trial; any widely used form of HPV testing is acceptable (including but not limited to HPV in situ hybridization [ISH], p16 testing [immunohistochemistry (IHC)], HPV16 testing, polymerase chain reaction [PCR], hybrid capture, etc)

  • Availability of formalin-fixed, paraffin-embedded (FFPE) tissue and blood

    • FFPE: >=14 slides containing tumor, 18 recommended

      • 7-10 slides 5 um thick, AND 7-10 slides 10 um thick, and cut with a clean blade (use new blade if possible or clean vigorously to avoid RNA/DNA, RNase contamination)
    • Blood: two 10 cc ethylenediaminetetraacetic acid (EDTA) purple top tubes (blood); two 2 ml cryovials (serum)
  • Patients with human immunodeficiency virus (HIV), not requiring highly active antiretroviral treatment (HAART) therapy are eligible
  • Life expectancy of greater than 8 weeks
  • Leukocytes >= 2,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits (unless proven Gilbert's disease, which after principal investigator [PI] approval patient may be included)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Creatinine within 1.5 X normal institutional limits
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • Ability to understand and the willingness to sign a written informed consent document
  • Fasting glucose of =< 120 mg/dl and glycosylated hemoglobin (HbA1c) =< 7.5%

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
  • Patients may not be receiving any other investigational agents
  • Patients with known, active brain metastases should be excluded from this clinical trial; patients with treated brain metastases stable for >= 12 weeks are eligible
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus or cetuximab
  • Concurrent life-threatening diseases: patients with diseases which with reasonable certainty do not limit life expectancy to 12 months or less are eligible; assessment of such concurrent illnesses should be by the principal investigator
  • Use of strong inhibitors/inducers of CYP3A4 is not permitted
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study
  • Breastfeeding should be discontinued if the mother is treated with temsirolimus
  • HIV-positive patients with normal immune function (CD4 count > 200) are eligible if there are no drug interactions with temsirolimus or cetuximab; patients with impaired immune function are ineligible due to the risk of additional immunosuppression from temsirolimus therapy
  • Concurrent administration of temsirolimus with vaccinations is to be avoided and a 14-day window from administration of the vaccine is advised; in emergent situations this policy may be revisited by the PI if deemed important for the patient's health
  • Poorly controlled hyperglycemia (HbA1C > 7.5%) or hyperlipidemia are exclusion criteria; hyperglycemia or hyperlipidemia need to be appropriately managed and controlled
  • Concurrent use of warfarin is allowed, but requires close monitoring of prothrombin time (PT)/international normalized ratio (INR)
  • Patients with clinically significant pneumonitis/pulmonary infiltrates unless there is a known and treatable cause for the condition

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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm A (cetuximab and temsirolimus)
Patients receive temsirolimus IV over 30-60 minutes and cetuximab IV over 1-2 hours once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Temsirolimus
Given IV
Other Names:
  • Torisel
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779
Biological: Cetuximab
Given IV
Other Names:
  • Erbitux
  • IMC-C225
  • Chimeric Anti-EGFR Monoclonal Antibody
  • Chimeric MoAb C225
  • Chimeric Monoclonal Antibody C225
EXPERIMENTAL: Arm B (temsirolimus)
Patients receive temsirolimus as in Arm A. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may cross over to Arm A.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Temsirolimus
Given IV
Other Names:
  • Torisel
  • CCI-779
  • CCI-779 Rapamycin Analog
  • Cell Cycle Inhibitor 779
  • Rapamycin Analog
  • Rapamycin Analog CCI-779

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: From start of treatment to time of progression or death from any cause, assessed up to 5 years
Progression determined using RECIST criteria: >=20% increase in the sum of the longest diameters of target lesions from nadir, occurrence of new lesions, or progression of non-target lesions.
From start of treatment to time of progression or death from any cause, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to 5 years
Time from randomization until death from any cause
Up to 5 years
Overall Response Rates (OR)
Time Frame: Up to 5 years
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Statistics reported are for Overall Response (OR) = CR + PR.
Up to 5 years
PFS vs. Historical Control Cohort
Time Frame: From start of treatment to time of progression or death of any cause, assessed at 4 months
PFS at 4 months in Arm A and Arm B will each be compared with a 4-month historical control rate of 21.4%. The historical data appears in two publications, an ASCO abstract: Abidoye, ASCO Annual Meeting 2006: 5568 and de Souza, Davis, et al, Clin Cancer Res 2012; 18(8):2336-2343.
From start of treatment to time of progression or death of any cause, assessed at 4 months
Grade 3 or Higher Hematological Toxicity
Time Frame: Up to 5 years
Incidence of hematological toxicities at least possibly related to study drug, graded based on Common Terminology Criteria for Adverse Events version 4
Up to 5 years
Percentage of Responses After Crossover From Control Arm to the Combination Arm, Assessed According to RECIST
Time Frame: Up to 5 years
Percentage of responses (if any) after crossover from the control arm to the combination arm will be evaluated qualitatively. This is includes complete and partial responses, and is different from Outcome Measure 8 below, which includes complete and partial responses as well as stable disease.
Up to 5 years
PFS of Myofibroblast (+) Cohort
Time Frame: From start of treatment to time of progression or death of any cause, assessed up to 5 years
From start of treatment to time of progression or death of any cause, assessed up to 5 years
Percentage of Responses/Disease Stabilization for Patients Crossing Over to the Combination Therapy After Progressing on Arm B.
Time Frame: Up to 5 years
Assessed according to RECIST. This is includes complete and partial responses as well as stable disease, and is different from Outcome Measure 6 above, which includes only complete and partial responses.
Up to 5 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Tanguy Seiwert, University of Chicago Comprehensive Cancer Center P2C

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

November 1, 2010

Primary Completion (ACTUAL)

December 1, 2013

Study Completion (ACTUAL)

December 1, 2013

Study Registration Dates

First Submitted

December 7, 2010

First Submitted That Met QC Criteria

December 7, 2010

First Posted (ESTIMATE)

December 8, 2010

Study Record Updates

Last Update Posted (ACTUAL)

March 27, 2017

Last Update Submitted That Met QC Criteria

February 23, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2011-02596 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • N01CM62201 (U.S. NIH Grant/Contract)
  • P30CA014599 (U.S. NIH Grant/Contract)
  • N01CM00071 (U.S. NIH Grant/Contract)
  • N01CM00099 (U.S. NIH Grant/Contract)
  • CDR0000689896
  • UCCRC-10-428-B
  • 10-428-B (OTHER: University of Chicago Comprehensive Cancer Center P2C)
  • 8692 (OTHER: CTEP)

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.

Clinical Trials on Recurrent Hypopharyngeal Squamous Cell Carcinoma

Clinical Trials on Laboratory Biomarker Analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bosnia & Herzegovina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe