Symptoms and General Pathology

All Conditions

Neoplasms

Mouth and Tooth Diseases

Rare Diseases

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Carcinoma, Verrucous

Squamous Cell Carcinoma of Head and Neck

Salivary Gland Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Mouth Neoplasms

Mouth Diseases

Stomatognathic Diseases

Salivary Gland Diseases

Oral Squamous Cell Carcinoma

Tongue Cancer

Oral Cancer

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Cetuximab

Sirolimus

Immunoglobulins

Temsirolimus

MTOR Inhibitors

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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.

Laboratory Biomarker Analysis

Tanguy Seiwert

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.

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

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

Progression determined using RECIST criteria: \>=20% increase in the sum of the longest diameters of target lesions from nadir, occurrence of new lesions, or progression of non-target lesions.

Time from randomization until death from any cause

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Statistics reported are for Overall Response (OR) = CR + PR.

PFS at 4 months in Arm A and Arm B will each be compared with a 4-month historical control rate of 21.4%. The historical data appears in two publications, an ASCO abstract: Abidoye, ASCO Annual Meeting 2006: 5568 and de Souza, Davis, et al, Clin Cancer Res 2012; 18(8):2336-2343.

Incidence of hematological toxicities at least possibly related to study drug, graded based on Common Terminology Criteria for Adverse Events version 4

Percentage of responses (if any) after crossover from the control arm to the combination arm will be evaluated qualitatively. This is includes complete and partial responses, and is different from Outcome Measure 8 below, which includes complete and partial responses as well as stable disease.

Assessed according to RECIST. This is includes complete and partial responses as well as stable disease, and is different from Outcome Measure 6 above, which includes only complete and partial responses.

National Cancer Institute (NCI)

Arm A (Cetuximab and Temsirolimus)

Arm B (Temsirolimus)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Three patients from each treatment arm did not start treatment and are considered non-evaluable.

Dr. Tanguy Seiwert

Progression-free Survival (PFS)

Overall Survival (OS)

Overall Response Rates (OR)

PFS at 4 months in Arm A was compared with a 4-month historical control rate of 21.4%, using a one-sided test at the 0.05 significant level. The historical data appear in two publications, an ASCO abstract: Abidoye, ASCO Annual Meeting 2006: 5568, and de Souza, Davis, et al, Clin Cancer Res 2012; 18(8):2336-2343 (see Figure 1).

PFS at 4 months in Arm B was compared with a 4-month historical control rate of 21.4%, using a one-sided test at the 0.05 significant level. The historical data appear in two publications, an ASCO abstract: Abidoye, ASCO Annual Meeting 2006: 5568, and de Souza, Davis, et al, Clin Cancer Res 2012; 18(8):2336-2343 (see Figure 1).

Note: Each arm is separately compared to an historical rate of 21.4%, based on a one-sided test at the 0.05 significant level. Since the 90% CIs each exclude 21.4%, the 4-month PFS rate in both arms exceeds the fixed historical control rate.

PFS vs. Historical Control Cohort

Grade 3 or Higher Hematological Toxicity

Percentage of Responses After Crossover From Control Arm to the Combination Arm, Assessed According to RECIST

Myofibroblast status was not determined. Concerns about the validity/technical feasibility as well as availability of the assay led us to decide to not perform the assay. We do not intend to perform this assay anymore.

PFS of Myofibroblast (+) Cohort

Percentage of Responses/Disease Stabilization for Patients Crossing Over to the Combination Therapy After Progressing on Arm B.

Overall Study

Spots Global Cancer Trial Database for stage ivb oral cavity verrucous carcinoma