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



Status:Completed
Conditions:Skin Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:November 2010
End Date:December 2013

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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.

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.

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
We found this trial at
24
sites
13001 E. 17th Pl.
Aurora, Colorado 80045
303-724-5000
University of Colorado Cancer Center - Anschutz Cancer Pavilion The University of Colorado Denver |...
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1500 East Medical Center Drive
Ann Arbor, Michigan 48109
800-865-1125
University of Michigan Comprehensive Cancer Center The U-M Comprehensive Cancer Center's mission is the conquest...
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22 South Greene Street
Baltimore, Maryland 21201
410-328-7904
University of Maryland Greenebaum Cancer Center The University of Maryland Marlene and Stewart Greenebaum Cancer...
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Baltimore, MD
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401 North Broadway
Baltimore, Maryland 21287
410-955-5000
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
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5841 S Maryland Ave
Chicago, Illinois 60637
1-773-702-6180
University of Chicago Comprehensive Cancer Center The University of Chicago Comprehensive Cancer Center (UCCCC) is...
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303 East Superior Street
Chicago, Illinois 60611
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2300 N Edward St
Decatur, Illinois 62526
(217) 876-8121
Decatur Memorial Hospital An American flag bearing only 48 stars waved above Decatur Memorial Hospital...
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1 Ingalls Dr
Harvey, Illinois 60426
(708) 333-2300
Ingalls Memorial Hospital As the area's only independent not-for-profit healthcare system, Ingalls has the ability...
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Harvey, IL
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535 Barnhill Dr
Indianapolis, Indiana 46202
(888) 600-4822
Indiana University Melvin and Bren Simon Cancer Center At the IU Simon Cancer Center, more...
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Iowa City, IA
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4500 San Pablo Rd S
Jacksonville, Florida 32224
(904) 953-2000
Mayo Clinic Florida Thousands of people come to Mayo Clinic in Jacksonville, Fla., annually for...
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600 Highland Ave
Madison, Wisconsin 53792
(608) 263-6400
University of Wisconsin Hospital and Clinics UW Health strives to meet the health needs of...
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2160 South 1st Avenue
Maywood, Illinois 60153
(888) 584-7888
Loyola University Medical Center Loyola University Health System is committed to excellence in patient care...
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8940 Wood Sage Rd
Peoria, Illinois 61615
(309) 243-3000
Illinois CancerCare-Peoria Illinois CancerCare, P.C. is a comprehensive practice treating patients withcancer andblood diseases. Our...
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Rochester, Minnesota 55905
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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Saint Louis, Missouri 63141
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Saint Louis Park, Minnesota 55416
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13400 E. Shea Blvd.
Scottsdale, Arizona 85259
480-301-8000
Mayo Clinic Arizona Mayo Clinic in Arizona provides medical care for thousands of people from...
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30 Ngan Shing Street
Shatin, Hong Kong
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Springfield, Illinois 62701
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801 N Rutledge St
Springfield, Illinois 62702
(217) 545-8000
Southern Illinois University School of Medicine At SIU School of Medicine, research includes biologically oriented...
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