Neoplasms

All Conditions

Symptoms and General Pathology

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Nasopharyngeal Carcinoma

Squamous Cell Carcinoma of Head and Neck

Salivary Gland Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Mouth Neoplasms

Mouth Diseases

Salivary Gland Diseases

Oral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Vorinostat

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Patients receive vorinostat PO QD or via PEG on days 1-5 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Cristina Rodriguez

This phase I/II trial studies the side effects of pembrolizumab and vorinostat in treating patients with squamous cell head and neck cancer or salivary gland cancer that has come back, has spread to other places in the body and/or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab together with vorinostat may be a better treatment for head and neck cancer or salivary gland cancer.

OUTLINE:

Patients receive vorinostat orally (PO) once daily (QD) or via percutaneous endoscopic gastrostomy (PEG) on days 1-5 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 8-12 weeks thereafter.

Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery

A Single Arm Phase I/II Study of MK-3475 Combined With Vorinostat for Recurrent Unresectable and/or Metastatic Squamous Cell Head and Neck Cancer and Recurrent Unresectable and/or Metastatic Salivary Gland Malignancies

Toxicities will be summarized as the number and percentage of patients with each type of toxicity, per Criteria for Adverse Events version 4.0

Radiologic assessments of measurable disease will be performed using radiographic imaging. RECIST 1.1 and immune response criteria will be used to assess response to therapy. Responses will be summarized as frequencies and percentages.

The Kaplan Meier methods will be used to estimate overall survival.

The Kaplan Meier methods will be used to estimate progression free survival.

National Cancer Institute (NCI)

University of Washington

Adverse events are collected from the first dose of Mk-3475 or Vorinostat, and are collected through 30 days post the last dose of therapy.

MK-3475 combined with vorinostat in HNSCC patients

Head and Neck Squamous Cell Carcinoma

MK-3475 combined with vorinostat in SGC patients

Salivary Gland Carcinoma

Head and Neck Squamous Cell Carcinoma patients

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

RMHNSCC with the following primary sites:nasopharynx, paranasal sinus, nasal cavity, skin/cutaneous sites. Pts with unknown HN primary sites will be enrolled. Patients with biopsy proven RMSGC be eligible as well

Adrenal insufficiency

ALT increase

Anorexia

Arthiritis

AST increase

Cough

Increased Creatinine

Dermatitis

Diarrhea

Fever with leukocytosis

Fatigue

Hyponatremia

Hypothyroidism

Colitis and Ileitis

Malaise

Nausea

Nephritis

Pneumonitis

Neuritis

Tracheitis/Epiglottitis

Vomiting

AEs experienced with MK-3475 combined with vorinostat in HNSCC patients

AEs experienced with MK-3475 combined with vorinostat in salivary gland carcinoma patients

Only G3 toxicities and toxicities requiring dose hold/reduction recorded.

Incidence of Toxicity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

partial response

stable disease

progressive disease

Head and Neck Squamous Cell

6 patients were not evaluated as they did not have at least 1 set of follow up scans while on study, (N=2 salivary patients, N=4 SCC patients)

Objective Response Rate

Overall Survival

Progression Free Survival

MK-3475 combined with vorinostat,HNSCC patients

MK-3475 combined with votinostat, SGC patients

Overall Study

Carcinoma, Verrucous

Oral Squamous Cell Carcinoma

Tongue Cancer

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Cetuximab

Sirolimus

Immunoglobulins

Temsirolimus

MTOR Inhibitors

Immunoglobulins, Intravenous

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Protein Kinase 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.

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.

Arm A (Cetuximab and Temsirolimus)

Arm B (Temsirolimus)

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery	NCT02538510	Head and Neck S... Recurrent Nasal... Recurrent Nasop... Recurrent Saliv... Squamous Cell C... Stage III Major... Stage III Nasal... Stage III Nasop... Stage IV Nasoph... Stage IVA Major... Stage IVA Nasal... Stage IVB Major... Stage IVB Nasal... Stage IVC Major... Stage IVC Nasal...	Laboratory Biom... Pembrolizumab Vorinostat	18 Years -	University of Washington
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)

Spots Global Cancer Trial Database for stage ivc major salivary gland carcinoma