Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Oral Squamous Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* Nivolumab to be delivered at a pre-determine dose for two weeks
* Ipilimumab to be delivered at a pre-determine dose for one week
* Blood Sample Collected
* Standard of Care Surgery

* Nivolumab to be delivered at a pre-determine dose for two weeks
* Blood Sample Collected
* Standard of Care Surgery

Standard of Care Surgery

Jonathan Schoenfeld, MD

This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for Squamous Cell Carcinoma of the oral cavity.

The following drugs are involved in this study:

* Nivolumab (Opdivo™)
* Ipilimumab (Yervoy™)

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The purpose of this study is to evaluate effectiveness (how well the drug/s work) of Nivolumab or Nivolumab combined with Ipilimumab prior to standard of care surgery.

Nivolumab and Ipilimumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells. Both nivolumab and Ipilimumab have been demonstrated to activate the immune system to attack cancer cells in laboratory studies and in patients with different types of cancers.

Nivolumab (Opdivo ™) has been approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma (a type of skin cancer), and specific types of previously treated advanced lung and kidney cancers. Ipilimumab (Yervoy™) is approved by the FDA for the treatment of metastatic melanoma.

Because Nivolumab and Ipilimumab help the immune system work in different ways, the combination of Nivolumab and Ipilimumab was tested in laboratory studies. The data from these studies suggested that giving the two drugs together could be of benefit to patients, and this was indeed found to be the case in patients with melanoma. The combination of Nivolumab and Ipilimumab is now FDA approved as treatment for patients with metastatic melanoma. However, the use of Nivolumab as well as Ipilimumab alone or in combination for the treatment of patients with head and neck cancer is not approved. Results from clinical trials investigating the safety and efficacy of Nivolumab and Ipilimumab in patients with head and neck cancer are not available at this time.

In the proposed study, either Nivolumab or the combination of Nivolumab and Ipilimumab is being tested is being tested prior to surgery to remove cancers of the oral cavity. By stimulating the immune system to attack cancer cells, these drugs may cause the cancer to decrease in size prior to surgery and prevent the cancer from coming back.

Window Study of Nivolumab With or Without Ipilimumab in Squamous Cell Carcinoma of the Oral Cavity

Response rate to window treatment with single agent nivolumab or nivolumab combined with ipilimumab is determined using bidirectional measurements (product of longest 2 diameters of lesions) of primary and nodal lesions to be removed at the time of surgery.

Responders will have demonstrated any reduction in overall tumor volume as determined by the product of the longest perpendicular bidirectional tumor measurements.

Outcome measure includes number of participants with treatment-related adverse events as assessed by CTCAE v4.0, number of dose-limiting toxicities in safety run-ins following a 3 + 3 design, and delays to surgery.

Determining the radiologic response rate following the window treatment as determined by RECIST v1.1.

Pathologic response in the primary tumor was assessed using a quantitative grading scheme:

pathologic tumor response \[nonviable tumor\] PTR0 = no or \<10% response PTR1 = ≥10% PTR2 = ≥50%

Progression-free survival is defined as the time between first study treatment and either recurrent disease or death. Recurrent disease includes a local failure, regional failure, or distant metastasis.

Overall survival is defined as the time between first study treatment and death.

Bristol-Myers Squibb

Dana-Farber Cancer Institute

Principal Investigator

The descriptions and grading scales found in the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.0) were utilized for AE reporting.

* Nivolumab to be delivered at a pre-determine dose for two weeks
* Ipilimumab to be delivered at a pre-determine dose for one week
* Blood Sample Collected
* Standard of Care Surgery

Nivolumab

Ipilimumab

Standard of Care Surgery

Nivolumab With Ipilimumab

* Nivolumab to be delivered at a pre-determine dose for two weeks
* Blood Sample Collected
* Standard of Care Surgery

Nivolumab

Standard of Care Surgery

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Jonathan Schoenfeld, M.D. M.P.H.

Thirty patients were treated from 2016 to 2019. One patient was excluded from efficacy analyses as she was ineligible because of evidence of distant metastatic disease at baseline.

Percentage of Participants With a Volumetric Response Rate to Treatment

Delays to Surgery

Dose-Limiting Toxic Effects during Safety Run-In

Grade 3-4 Events At Least Possibly Related to Protocol Treatment

Safety and Tolerability of Protocol Treatment

For this analysis, patients with no radiographically measurable lesions on imaging review were excluded. Thirty patients were treated from 2016 to 2019. One patient was excluded from efficacy analyses as she was ineligible because of evidence of distant metastatic disease at baseline.

Percentage of Participants Demonstrating Objective Response Using RECIST Criteria

PTR1

PTR2

Percentage of Participants Demonstrating Pathological Response

All participants enrolled in both trial cohorts.

All Participants

Participant One Year Progression-Free Survival Percentage

Participant Overall Survival Percentage

Pre-Surgery Intervention

Post-Surgery Follow-Up

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antirheumatic Agents

Vaccines

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

* Standard of care surgery
* Apheresis (between Day -28 and Day -7) approximately 12 weeks after surgery
* Cyclophosphamide 300 mg/m\^2 intravenously (Day -4)
* Personalized vaccine (Day 1)
* Booster dose of personalized vaccine (Day 43)
* Booster dose of personalized vaccine (Day 85)

Standard of care surgery

Apheresis

Personalized mature dendritic cell vaccine

Ramaswamy Govindan, M.D.

The purpose of this research study is to study the safety and immune response of people who receive a personalized dendritic cell vaccine with the intention of stimulating the immune system to react to lung cancer cells.

Tumor vaccines represent a promising area of clinical investigation in solid tumors based on evidence of clinical activity and minimal toxicity. The underlying hypothesis of this research is that immunization against tumor neoantigens is effectively required to elicit antigen-reactive T cells capable of recognizing and eliminating cancer. Moreover, both quantitative and qualitative improvements in CD8 immunity are necessary (but not sufficient) for clinical response and improved survival. The goal of this study is to build on our prior clinical trial results in melanoma by studying the immune response to tumor neoantigens in patients with stage 1 NSCLC.

Mature Dendritic Cell Vaccination Against Unique Immunogenic Peptides in Patients With Non Small Cell Lung Cancer (NSCLC)

-Blood for immunological response is drawn every week from Dose #1 to 6 weeks after Dose #3 (Day 1 to Day 126 = Week 18 and then every 4 weeks until Day 365)

Safety will be closely monitored after vaccination. Patients will be observed for 2 hours after the first dose and vital signs recorded every 30 minutes during that time period beginning at the start of the infusion. For each dose thereafter, patients will be observed in the treatment area for 30 minutes after the infusion. The following parameters will be assessed:

* Local signs and symptoms
* Systemic signs and symptoms
* Laboratory evaluations
* Adverse and serious adverse events
* Toxicity will be graded according to the NCI's CTCAE version 4.0.

These patients have been completed resected so there is no tumor response to monitor. CT scans evaluating for progression will be performed at baseline, following the third vaccine dose, and as per routine care during follow-up (generally every 3 months for the first year and every 6 months for the next 4 years thereafter).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Window Study of Nivolumab With or Without Ipilimumab in Squamous Cell Carcinoma of the Oral Cavity	NCT02919683	Head and Neck C...	Nivolumab Ipilimumab Standard of Car...	18 Years -	Dana-Farber Cancer Institute
Mature Dendritic Cell Vaccination Against Unique Immunogenic Peptides in Patients With Non Small Cell Lung Cancer (NSCLC)	NCT02419170	Carcinoma, Non-... Non-Small Cell ... Nonsmall Cell L...	Standard of car... Apheresis Cyclophosphamid... Personalized ma...	18 Years -	Washington University School of Medicine
Mature Dendritic Cell Vaccination Against Unique Immunogenic Peptides in Patients With Non Small Cell Lung Cancer (NSCLC)	NCT02419170	Carcinoma, Non-... Non-Small Cell ... Nonsmall Cell L...	Standard of car... Apheresis Cyclophosphamid... Personalized ma...	18 Years -	Washington University School of Medicine
Window Study of Nivolumab With or Without Ipilimumab in Squamous Cell Carcinoma of the Oral Cavity	NCT02919683	Head and Neck C...	Nivolumab Ipilimumab Standard of Car...	18 Years -	Dana-Farber Cancer Institute

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