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Neoadjuvant Immunoradiotherapy in Head & Neck Cancer

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ClinicalTrials.gov Identifier: NCT03247712
Recruitment Status : Recruiting
First Posted : August 14, 2017
Last Update Posted : February 18, 2019
Sponsor:
Collaborator:
Providence Cancer Center, Earle A. Chiles Research Institute
Information provided by (Responsible Party):
Providence Health & Services

Tracking Information
First Submitted Date  ICMJE August 8, 2017
First Posted Date  ICMJE August 14, 2017
Last Update Posted Date February 18, 2019
Actual Study Start Date  ICMJE January 15, 2018
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2017)
Number of patients with an Unplanned Delay to Surgery [Safety and Tolerability of Neoadjuvant Treatment] [ Time Frame: 6 weeks ]
Safety endpoint: Number of patients with an Unplanned Delay to Surgery defined as any change to scheduled surgery date considered to be at least possibly related to neoadjuvant treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03247712 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2017)
Number of patients with decrease in tumor size or number of lymph nodes involved [Efficacy of Neoadjuvant Treatment] [ Time Frame: 6 weeks ]
Efficacy endpoint: Number of patients with decrease in tumor size of greater than 10% or decrease in the number of lymph nodes involved by 10% by week 6.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neoadjuvant Immunoradiotherapy in Head & Neck Cancer
Official Title  ICMJE Neoadjuvant Immunoradiotherapy: Head & Neck Cancer (NIRT-HNC)
Brief Summary The purpose of this study is to test the safety of neoadjuvant immunoradiotherapy as a safe means of down-staging Head and Neck Squamous Cell Carcinoma (HNSCC) prior to surgical resection.
Detailed Description

This clinical trial uses nivolumab and radiotherapy prior to definitive surgical resection of tumors in patients with Head and Neck Squamous Cell Carcinoma (OHNSCC) with the primary objective of determining the safety and feasibility of preoperative immunoradiotherapy. In addition, tumor tissue, microbiome samples, and peripheral blood will be obtained for exploratory immunologic end points including measurements of tumor infiltrating immune cell populations based on flow cytometry and immunohistochemistry as well as circulating immunological parameters. This is the first study to evaluate the safety and efficacy of neoadjuvant radiation + PD-1 blockade in patients with HNSCC.

Estimated duration of 20 weeks: neoadjuvant immunoradiotherapy +/- surgery, followed by 6 doses of nivolumab 480mg IV q4wks +/- risk-adapted adjuvant therapy, per standard of care.

Phase I safety lead-in study (n = 6) evaluating the safety of neoadjuvant immunoradiotherapy in HNSCC, followed by phase II efficacy study (n = 28, total) to assess rate of down-staging after neoadjuvant immunoradiotherapy using Simon's two-stage design (futility assessment at n = 12).

The phase 1 portion of this study will require 6 patients and is therefore expected to complete in 6 months. Although non-surgical patients are eligible to enroll, they will not be counted toward accrual for either the primary safety endpoint, (as by definition, unplanned delay of surgery cannot exist); nor the secondary efficacy endpoint, as potential for surgical staging is absent.

So long as 2 or fewer surgical delays are observed (primary safety endpoint), the phase 2 portion of study will proceed (secondary efficacy endpoint). Patients will be followed for disease free and overall survival at 5 years.

Eligible patients may be enrolled unless a rate of unplanned surgical delay attributed to immunoradiotherapy is found to exceed 33% after enrollment of the first 6 patients. We estimate 10 to 20 patients per year will be enrolled.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Head and Neck Cancer
  • Head and Neck Squamous Cell Carcinoma
Intervention  ICMJE
  • Drug: Nivolumab
    Nivolumab 240mg IV q2wks or 480mg IV q4wks
    Other Name: Opdivo
  • Procedure: Surgical Resection
    Surgical Resection of Tumor
  • Radiation: Radiation (5 days)
    8Gy x 5 (Mon-Fri) GTV+3mm
  • Radiation: Radiation (3 days)
    8Gy x 3 (Monday, Wednesday, Friday) GTV+3mm
Study Arms  ICMJE
  • Experimental: Treatment Cohort 1
    Nivolumab administration (3 doses) and radiation (5 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).
    Interventions:
    • Drug: Nivolumab
    • Procedure: Surgical Resection
    • Radiation: Radiation (5 days)
  • Experimental: Treatment Cohort 2
    Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).
    Interventions:
    • Drug: Nivolumab
    • Procedure: Surgical Resection
    • Radiation: Radiation (3 days)
  • Experimental: Treatment Cohort 3
    Radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).
    Interventions:
    • Drug: Nivolumab
    • Procedure: Surgical Resection
    • Radiation: Radiation (3 days)
  • Experimental: Treatment Cohort 4
    Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses).
    Interventions:
    • Drug: Nivolumab
    • Procedure: Surgical Resection
    • Radiation: Radiation (3 days)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2019)
28
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2017)
6
Estimated Study Completion Date  ICMJE December 2026
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients with squamous cell carcinoma of the head and neck region, (including mucosal,cutaneous, or nodal) who are planned for surgical resection and in the opinion of the investigator are able to safely undergo neoadjuvant anti-PD-1 and radiation. In addition, the following are eligible (but will not contribute toward total accrual): non-surgical cases that are planned for palliative RT or that refuse or are unfit for definitive concurrent chemotherapy.
  2. HPV status as determined by p16 immunostain
  3. Cohort 3: HPV-positive patients only
  4. Cohort 4: HPV-negative patients only
  5. Age 18 years or above with ability to give informed consent, comply with the protocol, and sign a study-specific consent document. Patients with history of psychiatric illness must be judged by the investigator as able to understand the investigational nature and risks associated with the therapy.
  6. Eastern Cooperative Oncology Group (ECOG) performance status deemed suitable by investigator for study requirements.
  7. Laboratory values (most recent), must be within 6 weeks of week 0 on study:

    • WBC ≥ 2000/uL, ANC ≥ 1000/uL
    • Hgb > 8g/dL (patients may be transfused to reach this level)
    • Platelets > 50,000 cells/mm3
    • Creatinine ≤ 3 x ULN
    • AST/ALT ≤ 5 x ULN for subjects without liver metastasis; or ≤ 8 x ULN for subjects with liver metastasis, [per investigator brochure]
    • Total bilirubin ≤ 3 x ULN, (except subjects with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
    • Negative pregnancy test (bHCG urine or serum, women of childbearing potential only)
  8. Women of child-bearing potential (WOCBP) must agree to follow adequate contraceptive practices to avoid pregnancy for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (75 days) plus 30 days (duration of ovulatory cycle) for a total of 105 days post-treatment completion.
  9. Males who are sexually active with WOCBP must agree to follow adequate contraceptive practices to avoid pregnancy for the duration of treatment with study drug (s) plus 5 half lives of the study drug (75 days) plus 90 days (duration of sperm turnover) for a total of 165 days post-treatment completion.

Exclusion Criteria:

  1. Any clinical factors such as bleeding, active infection, or psychiatric factors that in the judgment of the investigator would preclude safe participation and compliance with study procedures.
  2. HNSCC for which radiation is not indicated during normal treatment course.
  3. Need for chronic maintenance with oral steroids ≥20mg daily prednisone equivalent; inhaled, topical or non-absorbed steroids are acceptable.
  4. History of or current active autoimmune disease, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome)], which in the judgment of the investigator poses an active and significant morbidity risk. Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary. Patient and investigator may opt to accept risk of autoimmune disease flare, based on shared-decision making with consideration of risk/benefit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Larisa Lundgren (503) 215-2614 Larisa.Lundgren@providence.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03247712
Other Study ID Numbers  ICMJE NIRT-HNC
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Providence Health & Services
Study Sponsor  ICMJE Providence Health & Services
Collaborators  ICMJE Providence Cancer Center, Earle A. Chiles Research Institute
Investigators  ICMJE
Principal Investigator: Rom Leidner, MD Providence Health and Services
PRS Account Providence Health & Services
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP