Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Docetaxel

Carboplatin

Antibodies

Antibodies, Monoclonal

Cisplatin

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Taxane

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will complete study procedures as outlined:

Preoperative Phase:

* Mandatory biopsy at baseline.
* Neoadjuvant treatment (2 cycles):

  * Cycles 1 - 2 ---Day 1 of 21-day Cycle: Predetermined doses of Pembrolizumab, Cisplatin (or Carboplatin) and Docetaxel.

Salvage Surgery:

-Primary tumor resection and/or lymph node dissection surgery 3-6 weeks from cycle 2 day 1

Adjuvant Phase:

-3-8 weeks post-surgery and upto a total of 15 cycles

--Cycles 3 - 17

---Day 1 of 21-day cycle: Predetermined dose of Pembrolizumab

Follow up appointments

Immunoglobulin G4 monoclonal antibody, via IV infusion

CISPLATIN

Kartik Sehgal, MD

This research study is evaluating effectiveness and safety of a combination of immunotherapy drug, pembrolizumab, with chemotherapy, as a possible treatment before and after surgery for squamous cell carcinoma of the head and neck (HNSCC). The combination of pembrolizumab and chemotherapy will be given prior to your surgery, while immunotherapy pembrolizumab will be continued for approximately 1 year after surgery.

The names of the study drugs involved in this research study are:

* pembrolizumab (a type of immunotherapy)
* docetaxel (a type of chemotherapy)
* cisplatin (a type of chemotherapy)
* carboplatin (a type of chemotherapy)

This is a Phase II, open-label, non-randomized, single arm, single-center interventional study of neoadjuvant chemoimmunotherapy with pembrolizumab, cisplatin (or carboplatin), and docetaxel followed by salvage surgery followed by adjuvant pembrolizumab therapy in patients with resectable recurrent squamous cell carcinoma of the head and neck (HNSCC). Pembrolizumab works by helping the immune system to fight HNSCC.

This research study involves screening for eligibility, study treatment visits including evaluations, radiologic scans, tumor biopsies, and blood tests.

The U.S. Food and Drug Administration (FDA) has not approved Pembrolizumab for squamous cell carcinoma of the head and neck (HNSCC) setting before and after surgery, but it has been approved for HNSCC in the advanced incurable setting when surgery is no longer possible or cancer has spread to parts of the body outside the head and neck region.

All other drugs used in this study have been approved by the FDA for squamous cell carcinoma of the head and neck (HNSCC) in the advanced incurable setting.

Participation in this research study is expected to last for up to 5 years.

It is expected that about 28 people will take part in this research study.

Merck Sharp \& Dohme LLC is supporting this research study and providing the study drug.

Preoperative Pembrolizumab and Chemotherapy in Resectable, Recurrent HNSCC

A Phase 2 Study of Preoperative Pembrolizumab and Chemotherapy Followed by Adjuvant Pembrolizumab in Resectable Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Major pathologic response (mPR) is defined as having ≤ 10% invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes as assessed by pathologists. Rate is the proportion of treated participants who experienced mPR.

Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation. All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Disease-Free Survival (DFS) based on the Kaplan-Meier method is defined as the time from surgery to the first recurrence or death from any cause, whichever occurs first. Participants alive without disease recurrence are censored at date of last disease evaluation.

Best radiological response are based on the RECIST 1.1 criteria, defined protocol section 11.2.4.

Merck Sharp & Dohme LLC

Dana-Farber Cancer Institute

Principal Investigator

42 gy of radiation therapy will be administered in 10 fractions.

39 gy of radiation therapy will be administered in 8 fractions.

32.5 gy of radiation therapy will be administered in 5 fractions.

Radiation Therapy: Dose per fraction of 4.2 Gy.

42 Gy Radiation Therapy

Radiation Therapy: Dose per fraction of 4.875 Gy.

39 Gy Radiation Therapy

Radiation Therapy: Dose per fraction of 6.5 Gy.

32.5 Gy Radiation Therapy

Medical College of Wisconsin Cancer Center Clinical Trials Office

Igli Arapi

Musaddiq Awan, MD

The primary purpose of this study is to determine the safe reduction of the treatment fractions to 10, 8, or 5, that may be delivered safely in resected head and neck squamous cell carcinoma (HNSCC) patients with intermediate pathologic risk features.

RATIONALE: Postoperative hypofractionated radiation is well established in many malignancies, yielding benefits in compliance, access to care, convenience, and cost savings. In several solid tumor types, short-course high dose-per-fraction (hypofractionated) post-operative radiation has shown excellent tolerability, reduced healthcare costs, improved compliance, and at least equivalent cancer control compared to conventional post-operative radiation (long course, low dose-per-fraction).(1-3) Despite advances in other malignancies, hypofractionated post-operative radiation is not used in previously untreated mucosal HNSCCs, for which an extended course of conventional post-operative radiation (usually 60 Gy in 2 Gy fractions delivered over six weeks) remains the standard. Hypofractionation has been stymied in the post-operative setting for HNSCCs primarily due to concerns of toxicity in treating a large mucosal field and an inability to spare critical structures such as the brain and spinal cord. These concerns were well-founded in the 1970s during the era of 2-dimensional radiotherapy when conventional HNSCC radiotherapy regimens were developed.(4) But because radiotherapy can be delivered far more precisely using intensity modulated radiation therapy (IMRT), it is hypothesized that post-operative radiation for HNSCCs can now be delivered safely in only five fractions delivered over one week.(3, 5, 6)

This study will use a time-to-event continual reassessment method (TITE-CRM) for assigning subjects to the radiation therapy dosages.

Hypofractionated Adjuvant Radiotherapy for Resected Head and Neck Cancers

A Phase I Study of Hypofractionated Adjuvant Radiotherapy for Resected Head and Neck Cancers (HART-HN)

This will be determined as the radiation dose with the minimum number of fractions at which there is no more than a 33% rate of dose-limiting toxicity (DLT) up to 12 months after completion of radiation treatment using the TITE-CRM design.

This measure is the number of subjects experiencing a dose-limiting toxicity. A dose-limiting toxicity is defined as an inability to complete radiation treatment within 30 days of the start of radiotherapy that is not deemed to be related to disease progression; OR an unacceptable toxicity within one year of treatment (Grade 4+ toxicity) that is probably or definitely related to radiation treatment as determined by the treating physician or a death within one year of treatment that is probably or definitely related to treatment.

This measure is the number of subjects alive at one year following the conclusion of scheduled radiation therapy.

This measure is the number of subjects showing disease progression in the head and neck by response evaluation criteria in solid tumors (RECIST) criteria.

This measure comprises a single five-item, Likert-style question with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. A higher score ('Strongly Agree') corresponds to a worse outcome.

This measure comprises 19 five-item, Likert-style questions with responses ranging from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') corresponds to worse traits or more severe symptoms.

This measure is the score for the "emotional" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to emotional health. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

This measure is the score for the "functional" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to the ability to function in daily life activities. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

This measure is the score for the "physical" domain comprising a subset of five-item, Likert-style questions of the MD Anderson Dysphagia Inventory Composite tool that assesses symptoms relevant to the ability to perform physical activities. Responses range from 'Strongly Agree' to 'Strongly Disagree'. Questions are worded such that higher scores ('Strongly Agree') correspond to worse traits or more severe symptoms.

Quality of life scale with 4 sub-scales and 12 items each related specifically to head and neck cancer quality of life. The Physical Health scale has 7 items, each rated 0-4. Scores range from 0-28 with a lower score indicating better quality of life. The Social Well Being scale has 7 items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life. The Emotional Well Being scale has 6 items, each rated 0-4. Scores range from 0-24 with a lower score indicating better quality of life. The Functional scale has 7 items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life. The remaining 12 items are all scored as 0-4 each, range for each item 0-4 with higher or lower score indicating better quality life depending on each individual item.

The Physical Well-being scale has seven items, each rated 0-4. Scores range from 0-28 with a lower score indicating better quality of life.

The Social Well-being scale has seven items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life.

The Emotional Well-being scale has 6 items, each rated 0-4. Scores range from 0-24 with a lower score indicating better quality of life.

The Functional Well-being scale has 7 items, each rated 0-4. Scores range from 0-28 with a higher score indicating better quality of life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Preoperative Pembrolizumab and Chemotherapy in Resectable, Recurrent HNSCC	NCT05726370	Head and Neck S... Head and Neck C... Resectable Head... Recurrent Head ...	Pembrolizumab CISPLATIN Carboplatin Docetaxel	18 Years -	Dana-Farber Cancer Institute
Hypofractionated Adjuvant Radiotherapy for Resected Head and Neck Cancers	NCT05120947	Resectable Head...	42 Gy Radiation... 39 Gy Radiation... 32.5 Gy Radiati...	18 Years -	Medical College of Wisconsin

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