Clinical trial NCT01256385: Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-12-08
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From start of treatment to time of progression or death from any cause, assessed up to 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Overall Response Rates (OR)
timeFrame: Up to 5 years
measure: PFS vs. Historical Control Cohort
timeFrame: From start of treatment to time of progression or death of any cause, assessed at 4 months
measure: Grade 3 or Higher Hematological Toxicity
timeFrame: Up to 5 years
measure: Percentage of Responses After Crossover From Control Arm to the Combination Arm, Assessed According to RECIST
timeFrame: Up to 5 years
measure: PFS of Myofibroblast (+) Cohort
timeFrame: From start of treatment to time of progression or death of any cause, assessed up to 5 years
measure: Percentage of Responses/Disease Stabilization for Patients Crossing Over to the Combination Therapy After Progressing on Arm B.
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Cancer Pavilion
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro Minnesota Community Oncology Research Consortium
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Shatin
country: China
facility: Chinese University of Hong Kong-Prince of Wales Hospital
state: Hong Kong
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center P2C
name: Tanguy Seiwert
role: PRINCIPAL_INVESTIGATOR
References: