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

Herbal and Botanical

Soy Bean

Patients receive soy isoflavones PO for approximately 14 days before undergoing surgery.

Soy Isoflavones

Survey Administration

Greg Wolf

This phase II clinical trial studies how well soy isoflavones work in preventing head and neck cancer in patients with stage I-IV head and neck cancer undergoing surgery. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of soy isoflavones may prevent head and neck cancer recurrence.

PRIMARY OBJECTIVES:

I. To determine if short term, preoperative (300 mg/day x 14 treatment days) soy isoflavone supplementation modulates p16 methylation (% CpG sites methylated) and expression of p16, cyclooxygenase 2 \[COX-2\], vascular endothelial growth factor receptor \[VEGF\], epidermal growth factor receptor \[EGFR\], interleukin-6 \[IL6\], p53 and B-cell lymphoma-extra large \[Bcl-xL\] in tumor and non-tumor adjacent mucosa of patients with head and neck squamous carcinoma undergoing curative tumor resection.

II. To estimate correlations of tumor p16 methylation (% CpG sites methylated) with expression of p16 and levels of, IL6, VEGF, and 15-F2t-isoprostane in serum and saliva.

SECONDARY OBJECTIVES:

I. Describe the toxicity of short-term, preoperative treatment with soy isoflavone.

II. To determine overall and relapse-free survival.

OUTLINE:

Patients receive soy isoflavones orally (PO) for approximately 14 days before undergoing surgery.

After completion of treatment, patients are followed up, within the routine cancer management schedule, at 3, 6, 12, and 24 months.

Soy Isoflavones in Preventing Head and Neck Cancer Recurrence in Patients With Stage I-IV Head and Neck Cancer Undergoing Surgery

A Phase II Trial of Preoperative Soy Isoflavone Supplementation and Molecular Markers in the Prevention of Head and Neck Squamous Carcinoma

The change in methylation will be analyzed in parallel using a linear repeated measures model. The fixed effects will be time (pre-treatment versus post-treatment), current smoking status (yes or no), their interaction, and tissue type (tumor or not). Satterthwaite's adjustment to the degrees of freedom will be applied to account for heteroscedasticity. The differential effect of soy isoflavone on tumor and non-tumor tissues between smokers and non-smokers will be assessed using linear contrasts.

Each of the tumor and mucosal markers will be dependent variables in repeated measures models that include serum and saliva markers as predictors. Graphical analyses will be used to characterize possible nonlinear relationships between variables. Linear or nonlinear regression, as appropriate, will be used to characterize the relationship between the putative predictors and outcomes. Subset analyses, considering, for example, differences in relationships between tumor markers and serum and saliva markers between smokers and non-smokers will be performed by means of indicator variables.

Overall survival at last follow-up will be determined.

Relapse-free survival will be determined at the last follow-up visit.

55 patients were enrolled. 3 patients did not undergo treatment. Only 52 patients were evaluable for toxicity.

Treatment (Soy Isoflavones)

55 patients were enrolled. 3 patients did not undergo treatment. 13 patients had insufficient tissue and were therefore not evaluable. Only the 39 evaluable patients were included in the analysis.

Gregory T. Wolf, M.D.

Mean Percent Change in p16 Methylation (% CpG Sites Methylated) in Tumor Tissue After Soy Isoflavone

We are seeking additional funding to hire the personnel to perform the serum/saliva markers. Until further notice markers will be unable to be analyzed.

Correlations of Tumor p16 Methylation Status With Serum/Saliva Markers of p16, IL6, and VEGF

The Number of Participants Alive at Follow-up

The Number of Participants Alive Without Relapse at Last Follow-up

Patients receive soy isoflavones PO for approximately 14 days before undergoing surgery.

55 patients were enrolled. 3 of these patients did not receive treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy	NCT01256385	Recurrent Hypop... Recurrent Laryn... Recurrent Laryn... Recurrent Lip a... Recurrent Metas... Recurrent Nasal... Recurrent Nasop... Recurrent Oral ... Recurrent Oroph... Recurrent Saliv... Salivary Gland ... Squamous Cell C... Stage IV Hypoph... Stage IV Nasoph... Stage IVA Laryn... Stage IVA Laryn... Stage IVA Lip a... Stage IVA Major... Stage IVA Nasal... Stage IVA Oral ... Stage IVA Oroph... Stage IVB Laryn... Stage IVB Laryn... Stage IVB Lip a... Stage IVB Major... Stage IVB Nasal... Stage IVB Oral ... Stage IVB Oroph... Stage IVC Laryn... Stage IVC Laryn... Stage IVC Lip a... Stage IVC Major... Stage IVC Nasal... Stage IVC Oral ... Stage IVC Oroph... Tongue Carcinom...	Cetuximab Laboratory Biom... Temsirolimus	18 Years -	National Cancer Institute (NCI)
Soy Isoflavones in Preventing Head and Neck Cancer Recurrence in Patients With Stage I-IV Head and Neck Cancer Undergoing Surgery	NCT02007200	Recurrent Hypop... Recurrent Laryn... Recurrent Laryn... Recurrent Lip a... Recurrent Oral ... Recurrent Oroph... Stage I Hypopha... Stage I Larynge... Stage I Larynge... Stage I Lip and... Stage I Oral Ca... Stage I Orophar... Stage II Hypoph... Stage II Laryng... Stage II Laryng... Stage II Lip an... Stage II Oral C... Stage II Oropha... Stage III Hypop... Stage III Laryn... Stage III Laryn... Stage III Lip a... Stage III Oral ... Stage III Oroph... Stage IV Hypoph... Stage IVA Laryn... Stage IVA Laryn... Stage IVA Lip a... Stage IVA Oral ... Stage IVA Oroph... Tongue Carcinom...	Laboratory Biom... Soy Isoflavones Survey Administ...	19 Years - 79 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iva laryngeal verrucous carcinoma