Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Cisplatin

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* MK-3475 will be given intravenously once approximately 2-3 weeks prior to standard of care surgery.
* Adjuvant therapy will be dictated by surgical pathology and occurs after standard of care surgery and will consist of:

  * risk-based intensity modulated radiation therapy consisting of 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions)once-daily fraction size (total of 30 fractions)
  * optional image-guided radiation therapy
  * risk-based cisplatin administered intravenously on Days 1, 22, and 43 of treatment course
  * MK-3475 will be given intravenously once every 3 weeks for a maximum of 6 doses if participant is considered high-risk based surgical pathology from standard of care surgery. These doses of MK-3475 will be given after surgery and after all acute toxicities of post-operative standard of care chemotherapy and radiation have resolved to grade 1 or less.

-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery)

MK-3475 (neoadjuvant)

Surgery

Intensity modulated radiation therapy

Image-guided radiation therapy

MK-3475 (adjuvant)

-Baseline, time of surgery (between day 14-24 inclusive), 3 months post surgery, 6 months post surgery, 9 months post surgery, 12 months post surgery

Peripheral blood

Douglas R Adkins, M.D.

The goal of this trial is to test the ability of MK-3475 (pembrolizumab) to improve locoregional recurrence and distant metastatic rates in high-risk patients with locally advanced head and neck squamous cell carcinomas (HNSCCs) that are treated with current standard of care surgical approaches.

Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

Immunotherapy With MK-3475 in Locoregionally Advanced, Surgically Resectable Head and Neck Squamous Cell Carcinoma

-The percentage of participants who developed local-regional recurrence within one year of surgery

-The percentage of participants who developed distant failure within one year of surgery. Distant disease is cancer that is found in another part of the body that is far away from where the original (primary) tumor first formed.

* Major pathologic treatment effect=pathologic tumor response (pTR).
* pTR was defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor): pTR-0 (\>10%), pTR-1 (10-49%), and pTR-2 (≥50%).

Reportable adverse events will be tracked for 30 days following the last day of study treatment. For the purposes of this protocol, reportable adverse events are events thought to be possibly, probably, or definitely related to MK-3475. Events thought to be probably or definitely related to surgery, adjuvant chemotherapy, or radiotherapy need not be recorded.

Merck Sharp & Dohme LLC

Washington University School of Medicine

The participant not assigned to an arm due to withdrawing before receiving any treatment was not followed for all-cause mortality, serious adverse events, or adverse events.

Cohort 1: Neoadjuvant MK-3475 and Adjuvant MK-3475

-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery).

Cohort 2: Neoadjuvant MK-3475

-Participants who did not receive any treatment and were not assigned to an arm (cohort).

Not Assigned to an Arm (Cohort)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

After enrollment of 20 patients, an interim analysis was performed to assess the feasibility to achieve the primary endpoint. The trial was amended to: a) close enrollment to cohort 1 b) addition of pTR-2 after neoadjuvant pembrolizumab in all patients as a co-primary endpoint, and c) addition of cohort 2.

Douglas R. Adkins, M.D.

-MK-3475 will be given once intravenously and then given again 21 days after dose 1 (14-24 days before standard of care surgery

Evaluable Cohort 1 participants for this outcome measure were those who had a high-risk pathology in the surgical specimen after one dose of neoadjuvant MK-3475 (pembrolizumab).

Locoregional Recurrence Rates in Cohorts 1 and 2

-Evaluable Cohort 1 participants for this outcome measure were those who had a high-risk pathology in the surgical specimen after one dose of neoadjuvant MK-3475 (pembrolizumab).

Distant Failure Rate in Cohorts 1 and 2

pTR-0

pTR-1

pTR-2

Only those participants enrolled in Cohort 1 were evaluable for this outcome measure.

Rate of Major Pathologic Treatment Effect in Cohort 1

Only those participants enrolled in Cohort 2 were evaluable for this outcome measure. One participant in Cohort 2 not evaluable for this outcome measure because the participant did not have surgery. One participant in Cohort 2 not evaluable because the data was missing.

Rate of Major Pathologic Treatment Effect in Cohort 2

Grades 1-2 fatigue (neoadjuvant period)

Grades 1-2 fever (neoadjuvant period)

Grades 1-2 tumor flare (neoadjuvant period)

Grades 1-2 AST increase (neoadjuvant period)

Grades 1-2 ALT increase (neoadjuvant period)

Grades 1-2 fatigue (adjuvant period)

Grades 1-2 hypothyroidism (adjuvant period)

Grades 3-4 hypothyroidism (adjuvant period)

Grades 1-2 AST increase (adjuvant period)

Grades 1-2 ALT increase (adjuvant period)

Grades 1-2 alkaline phosphatase increase (adjuvant period)

Grades 1-2 diarrhea (adjuvant period)

Only 12 participants in Cohort 1 received adjuvant MK-3475.

Number of Participants in Cohort 1 and 2 Who Experienced Reportable Adverse Events

One participant in Cohort 2 is not evaluable for the outcome measure because the participant did not have surgery.

Number of Surgical Complications and/or Delays in Cohorts 1 and 2

Rate of Distant Metastases (DM) in Cohorts 1 and 2

Overall Study

Symptoms and General Pathology

Recurrence

Pharmaceutical Solutions

Amino Acids

Antibodies

Cetuximab

Immunoglobulins

Arginine

Histidine

Ficlatuzumab will be administered as an IV infusion over 30-60 minutes, once every 2 weeks. Ficlatuzumab will be administered 30-60 minutes after the completion of the cetuximab infusion.

Cetuximab will be administered as an IV infusion once every 2 weeks. The first dose will be administered over 120 minutes (± 15 minutes). Subsequent doses may be infused over 60 minutes (± 15 minutes). The starting dose of cetuximab (dose tier 1) will be 500 mg/m2. Cetuximab will be administered prior to ficlatuzumab.

Ficlatuzumab Concentrate for Injection, 20 mg/mL, is formulated in 10 mM histidine buffer pH 5.8. The formulation also includes 142 mM arginine (for isotonicity) and 0.01% polysorbate 80. The product is sterile filtered and aseptically filled into washed and depyrogenated 5 mL glass vials.The product is a clear to slightly opalescent, colorless to slightly yellow, solution.

Ficlatuzumab Concentrate for Injection is to be administered by IV infusion as an admixture with normal saline solution. The admixture solution in an IV bag is connected to an infusion set containing a 0.22 µm low protein-binding in line filter. The filtered admixture solution is clear to slightly opalescent.

Ficlatuzumab is to be stored under refrigerated conditions (2o C- 8oC)

Ficlatuzumab

Cetuximab is supplied as a 50-mL, single-use vial containing 100 mg of cetuximab at a concentration of 2 mg/mL in phosphate buffered saline. The solution should be clear and colorless and may contain a small amount of easily visible white amorphous cetuximab particulates. Cetuximab can be administered via infusion pump or syringe pump, it must not be administered as an IV push or bolus. Cetuximab must be administered with the use of a low protein binding 0.22-micrometer in-line filter. Maximum infusion rate should not exceed 5 mL/min.

Store vials under refrigeration at 2C to 8C (36F to 46F). DO NOT FREEZE. Following the cetuximab infusion, a one-hour observation period is recommended.

James Ohr, DO

The epidermal growth factor receptor (EGFR) is both oncogene and prognostic biomarker in head and neck squamous cell carcinoma (HNSCC). EGFR's functional importance in HNSCC resulted in development of the first molecularly targeted strategy, the anti-EGFR monoclonal antibody cetuximab. Given the lack of therapeutic options for patients with recurrent/metastatic HNSCC after failure of cetuximab, there is strong scientific interest in understanding resistance in order to identify new therapies for this population. A possible resistance mechanism to anti-EGFR therapy in HNSCC is primary or compensatory activation of alternate growth factor receptors including c-Met. The MET oncogene encodes c-Met, an RTK bound exclusively by the ligand, hepatocyte growth factor (HGF). The HGF/c-Met signaling pathway converges with the EGFR network at both the PI3K/Akt and MAPK nodes. Laboratory data suggest the ability for reciprocal compensation between EGFR and c-Met. We hypothesize that HGF/c-Met pathway inhibition may overcome resistance to cetuximab in patients with HNSCC, such as those with clinical cetuximab resistance.

Ficlatuzumab (AV-299) is a humanized HGF-inhibitory immunoglobulin G1 (IgG1) monoclonal antibody. The primary objective of this phase 1b study is to find the recommended phase II dose (RP2D) of the combination of ficlatuzumab and cetuximab in patients with recurrent/metastaticHNSCC. The dose-finding study design will follow a Narayana k-in-a-row design with k set to 2 to target a 33% rate of dose-limiting toxicity (DLT). In the dose-finding phase, a total of 8 patients will be treated if no DLTs are observed or 14 patients if at least one DLT occurs. An expansion cohort will then proceed at RP2D until 12 patients have been treated at that dose level with the combination of ficlatuzumab and cetuximab. We will evaluate biomarkers of HGF/cMet pathway activation in baseline tissue, plasma and immune cells for a preliminary relationship with clinical activity.

This is a phase 1b, single arm, open-labeled study of ficlatuzumab and cetuximab in recurrent/metastatic HNSCC with biomarker correlatives. The primary objective of this study is to establish the recommended-for-phase II dose (RP2D) of the combination of ficlatuzumab and Cetuximab. In the absence of treatment delays due to adverse event(s), treatment may continue until disease progression or until one of the following criteria applies:

* Disease progression,
* Intercurrent illness that prevents further administration of treatment,
* Unacceptable adverse event(s),
* Patient decides to withdraw from the study, or
* General or specific changes in the patients condition render the patient unacceptable for further treatment in the judgment of the investigator.

After progressive disease, subjects will be followed for survival every 3 months for 2 years.

Cetuximab and ficlatuzumab are administered every other week on day 1 and 15 of a 28-day cycle. Ficlatuzumab will be administered as an IV infusion, over 30-60 minutes,10 mg/kg every 2 weeks, on the same day as the first dose of cetuximab. Ficlatuzumab will be administered 30-60 minutes after the completion of the cetuximab infusion. Cetuximab will be administered prior to ficlatuzumab as an IV infusion. The first dose will be administered over 120 minutes (± 15 minutes). Subsequent doses may be infused over 60 minutes (± 15 minutes).The starting dose of cetuximab (dose tier 1) will be 500 mg/m2 every 2 weeks.

Subjects will be monitored for adverse events and toxicity during study treatment and for 30 days after last dose of ficlatuzumab. Blood will be drawn for correlative studies at baseline, and at the end of every even cycle. Prior to initiation of protocol treatment, patients will undergo a mandatory research biopsy.

Ficlatuzumab and Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

A Phase 1b Study of Ficlatuzumab and Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma With Biomarker Correlatives

A dose escalation/de-escalation plan will be conducted according to an adaptive Narayana k-in-a-row design.45 We will select the dose of ficlatuzumab that is close to but does not exceed a 33% dose limiting toxicity (DLT) rate when administered with a fixed q2week dose of cetuximab. The observation period for identifying a DLT will be the first cycle, which consists of two doses of ficlatuzumab, or 4 weeks.In the dose-finding phase, a total of 8 patients will be treated if no DLTs are observed or 14 patients if at least one DLT occurs. If no DLTs are observed among the first 8 patients, the recommended for phase 2 dose (RP2D) will be set to dose tier 2. If a DLT is observed and 14 patients are treated and observed, the RP2D will be estimated from DLTs across all dose levels by isotonic regression. More than one patient can be enrolled at the same time.

Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used.

Progression-free survival (PFS) will be calculated from treatment initiation to disease progression or death from any cause or last follow up.

Survival will be measured from the date of entry on study. The preliminary clinical efficacy of the combination of cetuximab and ficlatuzumab will be described according to RR, median PFS, and median OS in: 1) the entire study population; 2) patients with prior cetuximab exposure treated at RP2D.

HNSCC tumors overexpress both HGF and c-Met as compared to adjacent tissue. The relationship of percent change in baseline sum diameter of index lesions to baseline cMet and HGF will be characterized by a linear, or if necessary, generalized linear or nonlinear regression model with appropriate confidence intervals.This exploratory endpoint seeks an early indication that overexpression of cMet or its ligand, HGF, may predict benefit from ficlatuzumab. For purposes of this endpoint, both cMet and HGF expression levels will be reported as semi-quantitative H-scores.

The prevalence of several mutations in HNSCC which interact with the HGF/c-Met signaling pathway have been identified, and may modulate the impact of pathway antagonism.These include PIK3CA (8%), PTEN (8%), and HRAS (4%) mutations.This will be evaluated by by whole exome sequencing.

Additional biomarkers in tumor and blood will be quantitatively measured and will be evaluated as predictors of tumor response and/or PFS in appropriate generalized linear models. Calculated p values for testing the significance of the prediction models will be adjusted for false discovery by the method of Benjamini and Hochberg

HNSCC is an immunosuppressive disease. Patients demonstrate lower absolute lymphocyte counts than healthy subjects, impaired natural killer (NK) cell activity and poor antigen-presenting function. Mechanistically, HGF inhibits dendritic cell activation. Dendritic cell and T cell phenotypes will be evaluated in archived biopsies (prior to cetuximab resistance) and pre ficlatuzumab research biopsies.

Additional biomarkers in tumor and blood will be quantitatively measured and will be evaluated as predictors of tumor response and/or PFS in appropriate generalized linear models. Calculated p values for testing the significance of the prediction models will be adjusted for false discovery by the method of Benjamini and Hochberg.Peripheral T cell and NK cell activity will be analyzed longitudinally before, during and after exposure to ficlatuzumab.

All patients will be evaluable for toxicity from the time of their first treatment with ficlatuzumab. The proportion of DLTs in each dosing cohort will be reported, as will the proportion of AEs in accordance with NCI CTCAE v.4 grading criteria.

AVEO Pharmaceuticals, Inc.

James J Lee

Assistant Professor of Medicine

Anti-Infective Agents

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

* Mitomycin C given on Day 1 every 5 weeks (each cycle is 5 weeks).
* Pegfilgrastim will be given on Day 2 of each cycle (subcutaneous injection)

Mitomycin-C

Pegfilgrastim

Peter Oppelt, M.D.

No agent is known to have efficacy in patients with incurable HNSCC that progressed with prior platin, 5-FU, cetuximab and taxane. Herein lies the unmet need to be addressed by this trial. Based on the preclinical and clinical data presented, the investigators propose that mitomycin C will have anti-tumor activity in these patients.

Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies

Phase II Trial of Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies

-EORTC QLQ-C30: this has a total score, one general QOL, and one "within the last week" subscale, as well as a general health item and a single overall QOL item. This study does not use current empirical guidelines for the EORTC-QLQ-30 global score with the understanding that both the magnitude and variance of scores vary considerably from patient to patient, from one time point to another and by such factors as disease condition, age, and comorbidity. The participants can choose from 1-4 with 1 being Not At All and 4 being Very Much.

-Cognitive Failures Questions (CFQ) - has 3 subscales describing perception, memory, and motor function. A change in 1 standard deviation will be considered a perceptible difference. The participants can choose a scale from 0-4 with 0 being Never and 4 being Very Often.

* TRR will be evaluated separately in p16- (HPV-unrelated) HNSCC patients and in p16+ (HPV positive) OPSCC patients using two optimal two-stage Simon designs. In both cases, the expected TRR is 10%. A TRR of 30% is considered a clinically significant increase.
* RECIST 1.1 will be used for this outcome.

* TRR will be evaluated in p16+ (HPV positive) OPSCC HNSCC patients
* RECIST 1.1 will be used for this outcome.

* PFS is defined as the duration of time from start of treatment to time of first radiologic confirmation of progression or death, whichever occurs first.
* Progressive disease per RECIST 1.1

  * Target lesions - At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
  * Non-target lesions - Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Cohort A: p16+ OPSCC and Cohort B: p16- HNSCC

Cohort A: p16+ OPSCC

Cohort B: p16- HNSCC

One participant in each arm were not evaluable for tumor response rate.

Tumor Response Rate (TRR)

Only participants enrolled post October 2020 are evaluable for this outcome measure.

Tumor Response Rate (TRR) for Participants Enrolled Post October 2020

One participant in each arm were not evaluable for this outcome measure.

Progression-free Survival (PFS)

Cohort A: p16+ OPSCC and Cohort B: p16- OPSCC

Number of Participants With Grade 3/4/5 Adverse Events

Overall Survival (OS)

Quality of Life as Measured by the EORTC QLQ-C30

Quality of Life as Measured by the Cognitive Failures Questions (CFQ)

EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined. Subjects will receive a total of up to 7 weekly intratumoral injections of EGFR antisense (or less if there is no identifiable tumor) starting 2 weeks prior to radiation. Patients will receive a total EGFR AS dose of 1.92 milligrams in 1.78 milliliters on each weekly treatment. This dose may be delivered equally in the same tumor site per weekly session, the primary tumor or cervical lymph nodes.

* Intratumoral EGFR AS injections weekly x 7 weeks (or less if there is no identifiable tumor), starting 2 weeks prior to radiation. The first EGFR AS injection must be given after cetuximab is administered. Subsequent EGFR AS injections can be given before or after cetuximab is administered. Injections will be in the primary and/or lymph nodes. One site will be injected per weekly session. If it is necessary the antisense injection can be scheduled within 1 business day of the original schedule date and then resume the original schedule
* EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined. The same lesion (primary tumor or lymph node) will be injected during treatment.

EGFR Antisense DNA

Julie Bauman, MD

The Epidermal Growth Factor Receptor (EGFR) is highly expressed in SCCHN and its overexpression is associated with poor patient outcome. EGFR is a promising target of anticancer therapy. We have developed EGFR antisense DNA as a safe and potentially efficacious treatment for SCCHN as shown in a previous phase I study conducted at the University of Pittsburgh. Cetuximab (Erbitux or C225) is a chimerized EGFR monoclonal antibody that has produced positive results in a phase III trial in SCCHN when added to radiation therapy and was approved by the FDA for the treatment of locally advanced SCCHN. Radiation plus cetuximab is considered a standard treatment, especially for patients who are not good candidates for chemotherapy. In the current study, we plan to evaluate the addition of intratumoral EGFR antisense DNA (EGFR AS) to standard radiation with concurrent cetuximab in patients.

Subject population We will enroll patients with SCCHN who are suitable for intratumoral injections of EGFR antisense. Please see eligibility criteria.

Treatment plan

EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined . Patients will receive a total of up to 7 weekly intratumoral injections of EGFR antisense (or less if there is no identifiable tumor) starting 2 weeks prior to radiation. Patients will receive standard radiation 70 Gy/200 cGy/daily, 5 days/week,excluding weekends and holidays, with concurrent cetuximab 250 mg/m2, after a loading dose of 400 mg/m2 2 weeks prior to starting radiation.

Statistical Design and Sample Size The study will be conducted in two-stages. In the first stage, 11 patients with stage IVA-C or recurrent disease will be evaluated for safety. If the regimen is deemed safe, a total of 31 patients with stage III or IVA-B, previously untreated SCCHN will be enrolled in the second stage of the study.

Safety and Efficacy of Radiation/Cetuximab Plus EGFR Antisense DNA for Head and Neck Squamous Cell Carcinoma

Safety and Efficacy Evaluation of Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Change in tumor size based on CT or MRI scans of the same tumor(s) of the head and/or neck as compared to baseline measurement.

National Cancer Institute (NCI)

University of Pittsburgh

Rare Diseases

Oral Squamous Cell Carcinoma

Antibodies, Monoclonal

Durvalumab

Immunoglobulin G

Immunoglobulins, Intravenous

Histone Deacetylase Inhibitors

Mocetinostat

Patients will start therapy with mocetinostat within 10 days of study enrollment. Mocetinostat will be given in 2 dose levels (n = 6 evaluable patients each) of 70mg three-times weekly and 90mg three-times weekly for 2 weeks.

Durvalumab will be given as a single infusion at a dose of 1500mg, over a period of 1-hour, on day 8 of the study.

Mocetinostat (MGCD0103) is a potent small molecule HDAC inhibitor that targets human HDAC isoforms. It is an orally bioavailable, second generation benzamide inhibitor of HDAC 1, 2, 3 and 11 with broad spectrum antitumor activity in vitro and in vivo.

Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against human PD-L1. It is selective for recombinant PD-L1 and blocks the binding of recombinant PD-L1 to the PD-1 and CD80 receptors.

Lillian Siu, MD

This is a Phase 1 Window of Opportunity study to evaluate the pharmacodynamic and immune effects of pre-operative therapy with Mocetinostat and Durvalumab on patients with squamous cell carcinoma of the oral cavity.

This is a single center, open-label, non-randomized, pre-operative window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative Mocetinostat and Durvalumab.

This study will involve treatment with Mocetinostat and Durvalumab, tests and procedures done for safety and the collection of blood samples for biomarker research. Tissue samples (fresh biopsy or archival tissue) will also be collected for biomarker research and evaluation.

Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity

Mirati Therapeutics Inc.

AstraZeneca

University Health Network, Toronto

LGK974

Patients will receive 10 mg of WNT974 daily by mouth.

WNT974

Francis Worden, M.D.

Given that up-regulation of the Wnt pathway has been identified as having a significant role in carcinogenesis in advanced head and neck squamous cell carcinoma, the investigator believes that inhibition of Porcupine via WNT974 will result in tumor control hence improvement in disease free and overall survival in these patients with a tolerable toxicity profile. As suggested by pre-clinical models, patients with a tumor harboring a Notch receptor (any of the four) loss of function mutation may have a greater response rate to treatment with WNT974. The investigator aims to address this question by administration of single agent WNT974 and following response radiologically along with close clinical follow up to monitor toxicities.

A Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma

An Open Label, Non-randomized Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma

Disease control rate will be assessed by examining the number of patients with stable disease, complete and partial response.

The overall response rate will be determined. Overall response will be defined as the sum of complete response + partial response.

Progression free survival in patients with metastatic head and neck cancer will be determined.

Toxicities associated with the treatment of WNT974 will be assessed.

University of Michigan Rogel Cancer Center

Mouth and Tooth Diseases

Mouth Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Cancer

Vasoconstrictor Agents

Central Nervous System Depressants

Nivolumab

Cocaine

Tyrosine

Patients will start therapy with sitravatinib within 10 days of study enrollment. Sitravatinib will be given at 120mg once daily on a continuous basis until 48 hours before planned surgery, or for a maximum period of 28 days.

Nivolumab will be given as a single infusion at a dose of 240mg, over a period of 30 minutes on Day 15 of the study.

Sitravatinib (MGCD516) is an orally-available, potent small molecule inhibitor of a closely related spectrum of tyrosine kinases, which has shown antitumor activity in a variety of in vitro and in vivo model systems.

Sitravatinib

Nivolumab (OPDIVO®) is a human IgG4 kappa immunoglobulin that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

This is a window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative drugs, Sitravatinib and Nivolumab.

This is a single center, open-label, non-randomized, pre-operative window of opportunity study for patients with resectable squamous cell carcinoma of the oral cavity who are considered suitable for curative-intent surgical resection, with pre-operative Sitravatinib and Nivolumab. A total of 12 patients who are evaluable for correlative studies, are planned for enrollment.

This study will involve treatment with Sitravatinib and Nivolumab, tests and procedures done for safety and the collection of blood samples for biomarker research. Tissue samples (fresh biopsy or archival tissue) will also be collected for biomarker research and evaluation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma	NCT02296684	Cancer of Head ... Head and Neck C... Neoplasms, Head... Carcinoma, Squa... Squamous Cell C... Squamous Cell C...	MK-3475 (neoadj... Surgery Intensity modul... Image-guided ra... Cisplatin MK-3475 (adjuva... Peripheral bloo...	18 Years -	Washington University School of Medicine
Ficlatuzumab and Cetuximab in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)	NCT02277197	Carcinoma, Squa... Squamous Cell C... Squamous Cell C...	Ficlatuzumab Cetuximab	18 Years -	University of Pittsburgh
Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies	NCT02369458	Squamous Cell C... Squamous Cell C...	Mitomycin-C Pegfilgrastim	18 Years -	Washington University School of Medicine
Safety and Efficacy of Radiation/Cetuximab Plus EGFR Antisense DNA for Head and Neck Squamous Cell Carcinoma	NCT00903461	Carcinoma, Squa... Squamous Cell C... Squamous Cell C...	EGFR Antisense ...	18 Years -	University of Pittsburgh
Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity	NCT02993991	Squamous Cell C... Squamous Cell C... Resectable Squa...	Mocetinostat Durvalumab	18 Years -	University Health Network, Toronto
A Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma	NCT02649530	Squamous Cell C...	WNT974	18 Years -	University of Michigan Rogel Cancer Center
A Phase II Trial Evaluating WNT974 in Patients With Metastatic Head and Neck Squamous Cell Carcinoma	NCT02649530	Squamous Cell C...	WNT974	18 Years -	University of Michigan Rogel Cancer Center
Sitravatinib (MGCD516) and Nivolumab in Oral Cavity Cancer Window Opportunity Study	NCT03575598	Squamous Cell C... Squamous Cell C... Squamous Cell C...	Sitravatinib Nivolumab	18 Years -	University Health Network, Toronto
Safety and Efficacy of Radiation/Cetuximab Plus EGFR Antisense DNA for Head and Neck Squamous Cell Carcinoma	NCT00903461	Carcinoma, Squa... Squamous Cell C... Squamous Cell C...	EGFR Antisense ...	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for squamous cell carcinoma, head and neck