Trial Title:
Preoperative Pembrolizumab and Chemotherapy in Resectable, Recurrent HNSCC
NCT ID:
NCT05726370
Condition:
Head and Neck Squamous Cell Carcinoma
Head and Neck Cancer
Resectable Head and Neck Squamous Cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Recurrence
Carboplatin
Pembrolizumab
Docetaxel
Conditions: Keywords:
Head and Neck Squamous Cell Carcinoma
Head and Neck Cancer
Resectable Head and Neck Squamous Cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Immunoglobulin G4 monoclonal antibody, via IV infusion
Arm group label:
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Other name:
MK-3475
Intervention type:
Drug
Intervention name:
CISPLATIN
Description:
Platinum agent, via IV infusion
Arm group label:
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Platinum agent, via IV infusion
Arm group label:
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Antineoplastic agent, via IV infusion.
Arm group label:
Pre-Operative Treatment + Salvage Surgery + Adjuvant Treatment
Other name:
Taxanes
Summary:
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)
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed locoregionally
recurrent squamous cell carcinoma of the head and neck (including primary sites,
such as oral cavity, oropharynx, larynx or hypopharynx carcinoma).
- Participants must be a candidate for salvage surgery.
- Participants must have documented time of ≥ 6 months from completion of prior
curative intent treatment for HNSCC (surgery and/or radiation therapy with/without
platinum chemotherapy or cetuximab targeted therapy) to diagnosis of local or
locoregional recurrence.
- Participants must be willing to undergo a mandatory pre-treatment biopsy and willing
to provide blood and tissue from the pre-treatment biopsy and at the time of
surgery. Exceptions may be made after discussion with sponsor if it is not medically
feasible to obtain a pre-treatment biopsy. Archival tissue may be collected in this
situation. Participants will be offered the opportunity to volunteer for optional
biopsies at the time of recurrence of disease.
- Participants may have any smoking history (no restrictions)
- Participants may have any Human Papilloma Virus (HPV) status of the tumor. Patients
with oropharyngeal cancer are required to undergo HPV testing with p16
immunohistochemistry and/or confirmatory HPV PCR or ISH testing
- Age ≥18 years
- ECOG performance status 0 or 1 (Karnofsky ≥70%, see Appendix A)
- Participants must have adequate organ and marrow function as defined below:
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin ≤ institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
- creatinine ≤ institutional ULN OR
- glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 unless data exists
supporting safe use at lower kidney function values, no lower than 30
mL/min/1.73 m2.
- Participants with known history or current symptoms of cardiac disease, or history
of treatment with cardiotoxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association Functional Classification. To
be eligible for this trial, participants should be class 2B or better.
- Because pembrolizumab and chemotherapy can be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation. Should a woman become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately.
- Male participants: A male participant must agree to use a contraception as detailed
in Appendix B of this protocol during the treatment period and for at least 180 days
after the last dose of study treatment and refrain from donating sperm during this
period.
- Female participants: A female participant is eligible to participate if she is not
pregnant (see Appendix B), not breastfeeding, and at least one of the following
conditions applies:
- a. Not a woman of childbearing potential (WOCBP) as defined in Appendix B OR
- b. A WOCBP who agrees to follow the contraceptive guidance in Appendix B during
the treatment period and for at least 180 days after the last dose of study
treatment.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Sinonasal, nasopharyngeal or cutaneous primary site of squamous cell carcinoma of
the head and neck
- Has known distant metastatic disease. Those with known brain metastases should be
excluded from this clinical trial, because of the poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation
of neurologic and other adverse events. However, baseline brain imaging is not
required prior to enrollment in the study if patients are asymptomatic
- Has had chemotherapy or radiotherapy for HNSCC in curative intent setting within 6
months prior to entering the study.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
CTLA-4, OX 40, CD137).
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study intervention.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug
- Has a known additional malignancy that is progressing or has required active
treatment within the past 2 years. Participants with basal cell carcinoma of the
skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast
carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
are not excluded
- Has a history of allergic reactions to agents used in study
- Has active autoimmune disease that has required systemic treatment in past 2 years
(ie, with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is allowed
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing
is required unless mandated by local health authority
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
unless mandated by local health authority.
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in the
best interest of the participant to participate, in the opinion of the treating
investigator.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Has not recovered from adverse events due to prior anti-cancer therapy (i.e., have
residual toxicities > Grade 2) with the exception of alopecia
- Has had an allogeneic tissue/solid organ transplant
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to study
registration (see Appendix B). If the urine test is positive or cannot be confirmed
as negative, a serum pregnancy test will be required. Pregnant women are excluded
from this study because pembrolizumab and chemotherapy agents have the potential for
teratogenic or abortifacient effects. Because there is an unknown but potential risk
for adverse events in nursing infants secondary to treatment of the mother with
pembrolizumab and chemotherapy, breastfeeding should be discontinued if the mother
is treated on this protocol.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Kartik Sehgal, MD
Phone:
617-632-3090
Email:
kartik_sehgal@dfci.harvard.edu
Investigator:
Last name:
Kartik Sehgal, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kartik Sehgal, MD
Phone:
617-582-7322
Email:
kartik_sehgal@dfci.harvard.edu
Start date:
May 20, 2023
Completion date:
May 20, 2030
Lead sponsor:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05726370
