Radiation Therapy and Pembrolizumab in Treating Patients with Head and Neck Squamous Cell Carcinoma That Is Recurrent or Cannot Be Removed by Surgery

Status: Active

Description

This phase II trial studies how well radiation therapy and pembrolizumab work in treating patients with head and neck squamous cell carcinoma that has come back or cannot be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving radiation therapy together with pembrolizumab may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Patients with biopsy proven locoregional recurrence or second primary SCCHN which is unresectable or the patient is unwilling to undergo resection
  • Have received only one prior radiation treatment course; prior radiation course must have been with curative intent
  • At least a 6 month interval since completion of prior radiation
  • Based on prior radiation records, have had most of the tumor volume (> 50%) previously radiated at doses >= 45 gray (Gy) without exceeding spinal cord tolerance (combining previous and future radiation dose to 1 cc of the spinal cord of =< 60 Gy)
  • Be willing and able to provide written informed consent/assent for the trial
  • Be willing to return to the center for all study-related follow up procedures, including blood collections and completion of imaging studies as required by the protocol
  • Be willing to undergo percutaneous endoscopic gastrostomy (PEG) placement, if necessary
  • Have at least one measurable area of disease based on RECIST 1.1 within the previously radiated field
  • Provide adequate tissue (core or incisional/excisional biopsy) prior to starting study treatment; this tissue will be used for PD-L1 analysis; fresh tissue or archival tissue sample can be used; if adequate tissue cannot be safely obtained than the patient may still be enrolled on the trial after discussion with the study principal investigator as long as fine-needle aspiration (FNA) was done to confirm recurrent/second primary head and neck squamous cell carcinoma (HNSCC)
  • Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Life expectancy of at least 12 weeks based on investigator estimate
  • Absolute neutrophil count (ANC) >= 1,500/mcL (within 21 days of treatment initiation).
  • Platelets >= 100,000/mcL (within 21 days of treatment initiation).
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (within 21 days of treatment initiation).
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) (within 21 days of treatment initiation).
  • Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 21 days of treatment initiation).
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases (within 21 days of treatment initiation).
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 21 days of treatment initiation).
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 21 days of treatment initiation).
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Proficiency in English language is required

Exclusion Criteria

  • Presence of distant metastatic disease
  • Is currently participating in or has participated in a study of an investigational agent or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has had a prior monoclonal antibody, chemotherapy, or targeted small molecule therapy within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier (alopecia is an exception) * Note: Subjects with =< grade 2 neuropathy or ototoxicity are an exception to this criterion and may qualify for the study * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • History of other malignancy within 5 years with the exception of prior SCCHN, adequately treated basal cell or squamous cell skin cancer, or carcinoma of the cervix
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule; subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; subjects with hypothyroidism stable on hormone replacement or Sjogren’s syndrome will not be excluded from the study
  • Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject 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
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-programmed death 1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), anti-programmed death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C antibody [Hep C Ab] is detected)
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment

Locations & Contacts

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Contact: Ana Ponce Kiess
Phone: 443-287-7528
Email: akiess1@jhmi.edu
University of Maryland / Greenebaum Cancer Center
Status: Active
Contact: Dan Paul Zandberg
Phone: 410-328-6505
Email: dzandberg@umm.edu

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: Active
Contact: Thomas James Galloway
Phone: 215-728-5536
Email: thomas.galloway@fccc.edu
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Contact: Dan Paul Zandberg
Phone: 412-864-7955
Email: zandbergdp@upmc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the progression free survival (PFS) in patients with locoregional inoperable recurrence or second primary squamous cell carcinoma of the head and neck (SCCHN) treated with reirradiation in combination with pembrolizumab.

SECONDARY OBJECTIVES:

I. To evaluate the safety and toxicity profile of the combination of reirradiation and pembrolizumab in patients with locoregional inoperable recurrence or second primary SCCHN.

II. To evaluate the best overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with locoregional inoperable recurrence or second primary SCCHN treated with reirradiation combined with pembrolizumab.

III. To evaluate the clinical benefit rate (CBR) by RECIST 1.1 in patients with locoregional inoperable recurrence or second primary SCCHN treated with reirradiation combined with pembrolizumab.

IV. To evaluate the time to in field progression in patients with locoregional inoperable recurrence or second primary SCCHN treated with reirradiation combined with pembrolizumab.

V. To evaluate the overall survival (OS) in patients with locoregional inoperable recurrence or second primary SCCHN treated with reirradiation combined with pembrolizumab.

VI. To evaluate patient reported quality of life as measured by questionnaires European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30 (QLQ-C30) and EORTC quality of life module for head and neck cancer (QLQ-H&N35) in patients with locoregional inoperable recurrence or second primary SCCHN treated with reirradiation combined with pembrolizumab.

EXPLORATORY OBJECTIVES:

I. To evaluate whether there is any correlation between PD-L1 expression on initial biopsy and the efficacy of pembrolizumab combined with reirradiation.

II. To evaluate whether there is any correlation between p16 expression in tumor biopsies and the efficacy of pembrolizumab combined with reirradiation.

III. To evaluate whether there is any correlation between percentages of cytotoxic T cells (CTL), regulatory T cells (Treg), or myeloid derived suppressor cells (MDSC) in the peripheral blood at initiation of therapy, and efficacy of pembrolizumab combined with reirradiation.

IV. To evaluate whether there is any correlation between changes in percentages of cytotoxic T cells, regulatory T cells, or myeloid derived suppressor cells over time, and efficacy pembrolizumab combined with reirradiation.

V. To evaluate whether there is any correlation between irradiated volume of vascular structures (as evaluated by dose-volume histogram) and efficacy of pembrolizumab combined with reirradiation.

OUTLINE:

Patients undergo radiation therapy twice daily (BID) 5 days a week for 5 weeks. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1 or day 2 of course 1 and day 1 of subsequent courses. Treatment repeats every 21 days for 16 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving partial response or stable disease may continue to receive pembrolizumab for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may be eligible for up to 1 year of additional pembrolizumab therapy if they progress after stopping pembrolizumab.

After completion of study treatment, patients are followed up for 30 days, at 3 and 6 months and then every 12 weeks thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pittsburgh Cancer Institute (UPCI)

Principal Investigator
Dan Paul Zandberg

Trial IDs

Primary ID 18-009
Secondary IDs NCI-2015-01783, s16-00016, HP-00061458
Clinicaltrials.gov ID NCT02289209