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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01256385
First received: December 7, 2010
Last updated: November 25, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
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 to 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 to 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
Biological: Cetuximab
Drug: Temsirolimus
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • PFS, evaluated using by RECIST [ Time Frame: From start of treatment to time of progression or death of any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    PFS of patients treated using temsirolimus with (Arm A) or without (Arm B) cetuximab will be compared.


Secondary Outcome Measures:
  • PFS of historic control cohort, evaluated using RECIST [ Time Frame: From start of treatment to time of progression or death of any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    PFS in Arm A and Arm B will be compared with historical controls using a one-sample binomial hypothesis test.

  • PFS of myofibroblast (+) cohort [ Time Frame: From start of treatment to time of progression or death of any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Proportion of responses/disease stabilization for patients crossing over to the combination therapy after progressing on Arm B [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • OS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Response rates [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Response rates will be compared between both treatment groups using a t-test.

  • Incidence of toxicities , graded based on Common Terminology Criteria for Adverse Events version 4 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    Analysis will be descriptive.

  • Number of responses after crossover from control arm to the combination arm, assessed according to RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Number of responses (if any) after crossover from the control arm to the combination arm will be evaluated qualitatively.


Estimated Enrollment: 80
Study Start Date: November 2010
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: Cetuximab
Given IV
Other Names:
  • Chimeric MoAb C225
  • Erbitux
  • IMC-C225
Drug: Temsirolimus
Given IV
Other Names:
  • CCI-779
  • Torisel
Other: Laboratory Biomarker Analysis
Correlative studies
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.
Drug: Temsirolimus
Given IV
Other Names:
  • CCI-779
  • Torisel
Other: Laboratory Biomarker Analysis
Correlative studies

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.

  Eligibility

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

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
  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: NCT01256385

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Northwestern University
Chicago, Illinois, United States, 60611
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 62702
Southern Illinois University
Springfield, Illinois, United States, 62702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, United States, 46845
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Metro-Minnesota CCOP
Saint Louis Park, Minnesota, United States, 55416
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
China, Hong Kong
Chinese University of Hong Kong-Prince of Wales Hospital
Shatin, Hong Kong, China, OX1 3UJ
Sponsors and Collaborators
Investigators
Principal Investigator: Tanguy Seiwert University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01256385     History of Changes
Other Study ID Numbers: NCI-2011-02596, NCI-2011-02596, CDR0000689896, UCCRC-10-428-B, 10-428-B, 8692, N01CM00099, P30CA014599, N01CM00071
Study First Received: December 7, 2010
Last Updated: November 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Verrucous
Head and Neck Neoplasms
Neoplasms, Unknown Primary
Salivary Gland Neoplasms
Mouth Diseases
Mouth Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Neoplastic Processes
Pathologic Processes
Salivary Gland Diseases
Stomatognathic Diseases
Cetuximab
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 27, 2014