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

Salivary Gland Squamous Cell Carcinoma Clinical Trial

— MAESTRO HN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01256385
• Other study ID #: NCI-2011-02596
• Secondary ID: NCI-2011-02596CD
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2010
• Last updated: December 22, 2015
• Start date: November 2010
• Est. completion date: December 2013

Study information

• Verified date: December 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• 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 Neoplasms
• 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

Intervention

Biological:
• Cetuximab
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Temsirolimus
Given IV

Locations

Country	Name	City	State
China	Chinese University of Hong Kong-Prince of Wales Hospital	Shatin	Hong Kong
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Mayo Clinic	Rochester	Minnesota
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS, evaluated using by RECIST	PFS of patients treated using temsirolimus with (Arm A) or without (Arm B) cetuximab will be compared.	From start of treatment to time of progression or death of any cause, assessed up to 5 years	No
Secondary	Incidence of toxicities , graded based on Common Terminology Criteria for Adverse Events version 4	Analysis will be descriptive.	Up to 30 days post-treatment	Yes
Secondary	Number of responses after crossover from control arm to the combination arm, assessed according to RECIST	Number of responses (if any) after crossover from the control arm to the combination arm will be evaluated qualitatively.	Up to 5 years	No
Secondary	OS		Up to 5 years	No
Secondary	PFS of historic control cohort, evaluated using RECIST	PFS in Arm A and Arm B will be compared with historical controls using a one-sample binomial hypothesis test.	From start of treatment to time of progression or death of any cause, assessed up to 5 years	No
Secondary	PFS of myofibroblast (+) cohort		From start of treatment to time of progression or death of any cause, assessed up to 5 years	No
Secondary	Proportion of responses/disease stabilization for patients crossing over to the combination therapy after progressing on Arm B		Up to 5 years	No
Secondary	Response rates	Response rates will be compared between both treatment groups using a t-test.	Up to 5 years	No