Clinical Trial 20490

• Overview

  Study Title:

  Keystroke: A Randomized Phase II Study of Pembrolizumab (Keytruda) Plus Stereotactic Re-irradiation versus SBRT Alone For Locoregionally Recurrent or Second Primary Head and Neck Carcinoma

  Summary:

  The purpose of the first part of this study is to determine whether adding pembrolizumab (study drug) to radiation (the usual approach for your cancer) is safe and tolerable in patients with head and neck cancer

  Objective:

  Primary Objective for Run-In Component To evaluate the safety of the addition of pembrolizumab (anti PD-1 immunotherapy) to re-irradiation with SBRT for patients with recurrent or new second primary head and neck squamous cell carcinoma Primary Objective for Phase II Trial To compare progression-free survival (PFS) for patients with recurrent or new second primary head and neck squamous cell carcinoma with SBRT re-irradiation with or without pembrolizumab

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy; Radiotherapy

  Medications:

  Pembrolizumab (Keytruda)

• Inclusion Criteria

  Inclusion Criteria:
  • Pathologically (histologically or cytologically) confirmed diagnosis of locoregional recurrent or any new primary squamous cell carcinoma of the head and neck (including of the nasopharynx or paranasal sinus) that is not amenable to curative resection. Patients for whom curative resection would be medically contraindicated and/or would impose excessive surgical risk are eligible. Patients who are medically and surgically resectable but for whom surgery would be associated with undue surgical morbidity are eligible. For purposes of this protocol, undue surgical morbidity would include total glossectomy; carotid artery resection; laryngectomy or pharyngolaryngectomy; and major ablative resection requiring free flap reconstruction. Patients with primary tumors that can be resected without the forgoing are ineligible.
  • Metachronous invasive SCC developing > 6 months after an index HNSCC, more than 3 cm from the index lesion;
  • SCC developing in the same region as the index SCC if > 36 months after the index diagnosis and if within 3 cm of a site where disease was completely resected or complete response was documented;
  • New SCC that is cytologically or molecularly distinct from index SCC (e.g. new HPV negative SCC with prior index SCC that was HPV positive). Tumor tissue testing for p16 status is required for base of tongue, soft palate, and tonsil cancer. If a p16 testing has been previously performed on an oropharynx cancer that has recurred, then repeat testing for p16 status is not required. Participants whose first cancer was an unknown primary must have p16 testing from either the new primary tumor or the recurrent cancer. Prior radiotherapy (RT) to the head and neck (30 Gy minimum). Disease must be limited to a single site or adjacent sites that can be treated in a single contiguous target volume for which the maximum total tumor dimension (GTV) must be > Patients who have undergone a recent biopsy (e.g. incisional) are eligible. Any preceding surgical procedure beyond a biopsy (e.g. debulking) must be reviewed as follows: Patients rendered free of gross disease are not eligible. Patients with gross residual disease postoperatively, must be reviewed by the Surgical Co-PI for determination of eligibility. Patients eligible for study must have cutaneous wounds healed for 4-6 weeks prior to the initiation of SBRT.
  • History/physical examination within 56 days prior to entry
  • Examination by a Radiation Oncologist and Medical Oncologist within 56 days prior to entry; [Note: Baseline dental assessment is strongly recommended prior to start of therapy but is not required for eligibility]
  • Contrast enhanced CT or MRI, of the tumor and neck within 56 days prior to entry.
  • Chest CT scan or full body PET/CT within 56 days prior to entry; patients with equivocal pulmonary nodules that are > Zubrod Performance Status of 0-1 within 28 days prior to entry.
  • 18 years of age or older
  • Adequate organ function as defined in protocol
  • Negative serum pregnancy test within 14 days prior to entry for women of childbearing potential. (Note: A pregnancy test must be repeated within 3 days prior to the administration of the first dose of pembrolizumab)

• Exclusion Criteria

  Exclusion Criteria:
  • Distant metastases.
  • Tumors that involve more than 180 degrees of the carotid artery on diagnostic CT or MRI of the neck within 56 days prior to entry. Investigators are encouraged to review the CT simulation imaging and ensure that tumor progression has not occurred whereby patients who were initially eligible based on diagnostic imaging, would be rendered ineligible based on CT simulation imaging (e.g. tumor size >7.5cm, skin involvement, >180 degrees of carotid encasement by tumor). If this does occur, the patient should be removed from the study and the Radiation Oncology Co-PIs should be notified via email. Note: It is strongly recommended that CT simulation be performed prior to entry.
  • Patients with gross skin involvement (i.e. tumor ulceration through the skin) are excluded. Patients with tumor approaching the skin but in which the overlying skin remains intact are eligible, providing that planning constraints can be achieved without the use of bolus.
  • Disease that requires two or more discontiguous target volumes will be ineligible. > Patients for whom the maximal total tumor dimension (GTV) is >7.5cm
  • Prior radiation to primary tumor within 6 months of entry
  • Prior systemic therapy, investigational agent or investigational device within 28 days of start of study treatment.
  • Surgical resection of the qualifying cancer is not permitted. (Patients who have undergone biopsies are eligible). Patients without radiographically apparent gross tumor are ineligible. For cases where an operation more extensive than a biopsy was performed but radiographically apparent gross residual tumor remains, will be reviewed by the Surgical Co-PI for determination of eligibility.
  • No concurrent treatment with other investigational agent or investigational device.
  • Prior therapy with a checkpoint inhibitor (eg anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapy).
  • Patients with immunodeficiency, or receiving systemic steroid, or any form of immunosuppressive therapy at the time of registration (e.g. history of human immunodeficiency virus - HIV). Use of physiologic doses corticosteroids may be approved with consultation with study chairs.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc.) is not considered a form of systemic therapy
  • Known active hepatitis B (positive test for virus surface antigen - HBsAg) or hepatitis C virus (e.g. positive HCV RNA qualitative test).
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Treatment with a live vaccine within 30 days of entry. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not allowed
  • Unstable angina and or congestive heart failure requiring hospitalization in the last 6 months.
  • Transmural myocardial infarction within the last 6 months.
  • Active bacterial or fungal infection requiring intravenous antibiotic at the time of registration; Note: If the infection resolves and the patient is on p.o. and still within, the required registration timeframe, then the patient is eligible
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of entry.
  • Other exclusions apply

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