Targeting PD-1 Therapy Resistance With Focused High or High and Low Dose Radiation in SCCHN

  • End date
    Oct 31, 2027
  • participants needed
  • sponsor
    Dana-Farber Cancer Institute
Updated on 28 January 2022
squamous cell carcinoma
neutrophil count
squamous cell carcinoma of head and neck
head and neck carcinoma


This research study is studying immunotherapy in combination with radiation therapy as a possible treatment for head & neck cancer that has worsened or spread to another organ or part of your body.

The immunotherapy involved in this study is: MK-3475 (pembrolizumab or KEYTRUDA).


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

MK-3475 is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance (particles not typically found in the body such as bacteria or viruses). Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients. MK-3475 is designed to restore the natural ability of the immune system to recognize and target cancer cells.

The FDA recently granted approval to MK-3475 as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). This study is testing whether using radiation in combination with MK-3475 will make this drug work better in participants that might otherwise be unlikely to benefit from this drug because they have not responded to either this same drug given without radiation or another similar drug.

Condition Head and Neck Cancer
Treatment Pembrolizumab, Radiation
Clinical Study IdentifierNCT03085719
SponsorDana-Farber Cancer Institute
Last Modified on28 January 2022


Yes No Not Sure

Inclusion Criteria

Pathologically confirmed squamous cell carcinoma of the head and neck with evidence of metastatic disease considered incurable by local therapies. Patients without pathologic or cytologic evidence of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
Patients must have evidence of radiologic or clinical disease progression during previous treatment with systemic PD-1 directed therapy, or have stable disease on prior PD-1 therapy (at least 6 doses) and/or have been deemed not to derive clinical benefit from PD-1 directed treatment
Patients must have least 3 measurable non-CNS based lesions that have not previously been irradiated. Palliative radiation must be potentially indicated for at least one of these lesions
Patients must agree to undergo a research biopsy, if tumor is accessible, at baseline (mandatory) and at the end of cycle 2 of pembrolizumab (optional)
Prior systemic therapy: Patients must be at least 2 weeks from prior chemotherapy, biological agents, immunotherapy or any investigational drug product, with adequate recovery of toxicity. For investigational agents, the minimum time from prior therapy is 5 half-lives if this is longer than 2 weeks in duration
Prior radiation therapy: Patients must be at least 2 weeks from prior radiation therapy
Concurrent administration of other cancer specific therapy during the course of this study is not allowed
Only patients 18 years and older are eligible. There is no upper age limit but the patients must be able to medically tolerate the regimen. Adverse event data are currently unavailable on the use immune checkpoint blockade for participants < 18 years of age, and thus children are excluded from this study
ECOG performance status <=1 (see Appendix A)
Ability to understand and the willingness to sign a written informed consent document
Female subjects of childbearing potential must have a negative serum pregnancy test at screening
Female and male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in section 5.7.1. Contraception is required prior to study entry and for the duration of study participation and 4 months after completion of pembrolizumab administration
\--Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject
Participants must have normal organ and marrow function as defined below
leukocytes 3,000/mcl
absolute neutrophil count 1,500/mcL
platelets 100,000/mcL
hemoglobin >= 9 g/dl
total bilirubin 1.5 institutional upper limit of normal (ULN)
AST(SGOT)/ALT(SGPT) 2.5 institutional ULN
AST(SGOT)/ALT(SGPT) For patients with documented liver metastases, 5 institutional ULN
creatinine 1.5 within normal institutional ULN OR
creatinine clearance 60 mL/min/1.73 m2 for participants with creatinine levels above institutional ULN
International normalized ratio (INR) or Prothrombin Time (PT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Activated Partial Thromboplastin Time (aPTT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Laboratory tests required for eligibility must be completed within 14 days prior study entry. Baseline tumor measurements must be documented from tests within 28 days of study entry. Other non-laboratory tests must be performed within 28 days of study entry

Exclusion Criteria

Metastatic disease impinging on the spinal cord or threatening spinal cord compression
Surgical fixation of bone lesion to be irradiated is required and indicated to provide mechanical stability
Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with previously diagnosed brain metastases are eligible if they have completed treatment at least 2 weeks prior to trial therapy initiation, are neurologically stable, and have recovered from the acute effects of radiotherapy or surgery. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for 2 weeks before the initiating protocol therapy. Treatment for brain metastases may include surgery, whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician
Participants who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or previous toxicity attributed to pembrolizumab or other PD-1 directed therapy that led to drug discontinuation
Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Clinically significant electrocardiogram (ECG) abnormality, including a marked Baseline prolonged QT/QTc ([QT interval/corrected QT interval], e.g., a repeated demonstration of a QTc interval >500 ms)
Pregnant women are excluded from this study because immunotherapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with immunotherapy, breastfeeding should be discontinued if the mother is treated on this protocol
Individuals with a history of a different malignancy are ineligible except for the following circumstances: if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; or if diagnosed and treated for cervical cancer in situ or basal cell or squamous cell carcinoma of the skin
HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for interaction between immunotherapy and these medications
Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non infectious pneumonitis
Active, suspected or prior documented autoimmune disease that has required systemic treatment in the last 2 years with immune modifying agents (e.g. replacement therapy such as thyroxine, insulin or physiologic corticosteroids is not an exclusion criteria)
The subject is known to be positive for HepBsAg, or HCV RNA
Lack of availability for follow up assessments
The investigator's belief that the subject is medically unfit to receive pembrolizumab and or unsuitable for any other reason
Has received a live vaccine within 30 days of planned start of study therapy
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How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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