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

NCT ID: NCT01256385

Last Updated: 2017-03-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2013-12-31

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Laryngeal Verrucous Carcinoma Recurrent Lip and Oral Cavity Squamous Cell Carcinoma Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma Recurrent Oral Cavity Verrucous Carcinoma Recurrent Oropharyngeal Squamous Cell Carcinoma Recurrent Salivary Gland Carcinoma Salivary Gland Squamous Cell Carcinoma Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary Stage IV Hypopharyngeal Squamous Cell Carcinoma Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma Stage IVA Laryngeal Squamous Cell Carcinoma Stage IVA Laryngeal Verrucous Carcinoma Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma Stage IVA Major Salivary Gland Carcinoma Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma Stage IVA Oral Cavity Verrucous Carcinoma Stage IVA Oropharyngeal Squamous Cell Carcinoma Stage IVB Laryngeal Squamous Cell Carcinoma Stage IVB Laryngeal Verrucous Carcinoma Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma Stage IVB Major Salivary Gland Carcinoma Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma Stage IVB Oral Cavity Verrucous Carcinoma Stage IVB Oropharyngeal Squamous Cell Carcinoma Stage IVC Laryngeal Squamous Cell Carcinoma Stage IVC Laryngeal Verrucous Carcinoma Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma Stage IVC Major Salivary Gland Carcinoma Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma Stage IVC Oral Cavity Verrucous Carcinoma Stage IVC Oropharyngeal Squamous Cell Carcinoma Tongue Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Temsirolimus

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Temsirolimus

Intervention Type DRUG

Given IV

Interventions

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Cetuximab

Given IV

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Temsirolimus

Given IV

Intervention Type DRUG

Other Intervention Names

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Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 CCI-779 CCI-779 Rapamycin Analog Cell Cycle Inhibitor 779 Rapamycin Analog Rapamycin Analog CCI-779 Torisel

Eligibility Criteria

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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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tanguy Seiwert

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center P2C

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Site Status

Ingalls Memorial Hospital

Harvey, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Central Illinois Hematology Oncology Center

Springfield, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Chinese University of Hong Kong-Prince of Wales Hospital

Shatin, Hong Kong, China

Site Status

Countries

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United States China

Other Identifiers

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NCI-2011-02596

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000689896

Identifier Type: -

Identifier Source: secondary_id

UCCRC-10-428-B

Identifier Type: -

Identifier Source: secondary_id

10-428-B

Identifier Type: -

Identifier Source: secondary_id

10-428-B

Identifier Type: OTHER

Identifier Source: secondary_id

8692

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00099

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02596

Identifier Type: -

Identifier Source: org_study_id

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