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Trial record 1 of 1 for:    NCT03317327
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REirradiation and Programmed Cell Death Protein 1 (PD-1) Blockade On Recurrent Squamous Cell Head and Neck Tumors (REPORT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03317327
Recruitment Status : Recruiting
First Posted : October 23, 2017
Last Update Posted : September 30, 2019
Bristol-Myers Squibb
Information provided by (Responsible Party):
Åse Bratland, Oslo University Hospital

Brief Summary:

Each subject will participate in the trial until death, drop out, or loss-to follow-up from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 28 days, each eligible subject will receive nivolumab. Two weeks after start of nivolumab the patients will receive radiotherapy (RT) to a total dose of 60 Gy, given as 1.5 Gy fractions twice daily for a total period of 4 weeks. Treatment with nivolumab will continue until disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the subject, noncompliance with trial treatment or procedures requirements, subject receives nivolumab for 12 months, pregnancy, or administrative reasons.

After the end of treatment, each subject will be followed for 30 days for adverse event monitoring serious adverse events (SAEs) will be collected for 90 days after the end of treatment. Patients without disease progression will have follow-up visits for 4 years after end of study therapy.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: Nivolumab Radiation: Radiotherapy (RT) Phase 1 Phase 2

Detailed Description:

In this study, the aim is to release the brake on the immune response by use of nivolumab, an inhibitory antibody against Programmed cell death protein 1 (PD-1). Nivolumab has shown efficacy and mild toxicity when given as monotherapy for HNSCC at a dose of 3.0 mg/kg every 2 weeks, which is the target dose in the present trial.

Radiotherapy is a powerful inducer of inflammation, and the expression of Programmed death-ligand 1 (PD-L1) is known to be enhanced by inflammatory cytokines, including interferon-gamma (IFNg). Experimental evidence from mice models have shown that radiotherapy induces increased PD-L1 expression in tumor tissue. Moreover, there is evidence suggesting that HNSCC with T-cell infiltration is more sensitive to radiotherapy. There is thus a strong rationale for combing PD-1 inhibitors with radiotherapy. However, this potential remains largely unexplored in humans. The investigators consider that head-and-neck cancer is a particularly attractive entity for investigating this therapeutic combination, because of i) the high radiosensitivity of this cancer form ii) the clinical efficacy of Programmed cell death protein 1 (PD-1) inhibitors as monotherapy in early clinical trials iii) the availability of tumor biopsies for translational/biomarker research.The RT given in the present study gives considerable side effects, related to inflammation that may be enhanced by Programmed cell death protein 1 (PD-1) blockade.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Exploratory
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: REPORT; REirradiation and PD-1 Blockade On Recurrent Squamous Cell Head and Neck Tumors
Actual Study Start Date : September 9, 2017
Estimated Primary Completion Date : November 2, 2023
Estimated Study Completion Date : November 2, 2040

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Nivolumab
Nivolumab, intravenous every 2nd week (1 cycle = 2 weeks), dose escalation schedule (1.0, 3.0 mg/kg), for a maximum of 12 months or until disease progression.
Drug: Nivolumab
Nivolumab is a humanized antibody used in cancer immunotherapy.
Other Name: Opdivo

Radiation: Radiotherapy (RT)
Radiotherapy (RT) will be given to a total dose of 60 Gy (1,5 Gy fractions twice daily) for a total period of 4 weeks

Primary Outcome Measures :
  1. Incidence, nature, and severity of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. [ Time Frame: 18 months (6 months after end of treatment) ]

Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: After 12 months ]
    defined as the time from inclusion to the time of radiographic progression (as assessed by RECIST) or death from any cause during the study

  2. Objective response rate (ORR) [ Time Frame: 3 years ]
    defined as the proportion of patients with an objective tumor response

  3. Overall survival (OS) [ Time Frame: 5 years ]
    defined as the time from the date of inclusion to the date of death from any cause

  4. Duration of response (DOR) [ Time Frame: 3 years ]
    among patients with an objective response

  5. Durable response rate (DRR) [ Time Frame: 3 years ]
    defined as the proportion of patients with an objective tumor response lasting at least 6 months

Other Outcome Measures:
  1. Immunological response [ Time Frame: 3 years ]
    as assessed by gene profiling, immunohistochemistry, T cell assays, characterization of cell suspensions from tumor and peripheral blood

  2. tumor evolution [ Time Frame: 3 years ]
    as assessed by gene profiling, immunohistochemistry, characterization of cell suspensions from tumor and peripheral blood

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 18 years or older
  • Recurrent or secondary primary squamous cell carcinoma originating from the oral cavity, oro/hypo-pharynx or larynx
  • Prior radiotherapy (46-70Gy)
  • Adequate newly obtained core or excisional biopsy of a recurrent tumor lesion
  • Measurable disease
  • Lesion available for biopsy during study treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy of more than 12 months
  • A minimum of 6 months since prior radiotherapy in the same area or minimum 4 weeks (28 days) since previous other cancer treatment
  • Human papillomavirus positive and negative disease allowed
  • Distant metastases allowed
  • Adequate organ function based on clinical examination and lab values
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug
  • Women must not be breastfeeding
  • WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
  • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo five half-lives. The terminal half-life of nivolumab is up to 25 days

Exclusion Criteria:

  • History of other prior malignancy, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin, cervical cancer stage IB and stage I prostate cancer considered not necessary to treat
  • Disease suitable for curative salvage surgery
  • Treatment with any investigational medicinal product (IMP) that may interfere with the study treatment, within 4 weeks prior to first administration of study drug.
  • Significant cardiac, pulmonary or other medical illness that would limit activity or survival
  • Pregnancy or lactation.
  • Known hypersensitivity to any of the components of the investigational product
  • Patients who test positive for hepatitis B, C or HIV.
  • Diagnosis of immunodeficiency or medical condition requiring systemic steroids or other forms of immunosuppressive therapy
  • Autoimmune disease that has required systemic therapy within the past 2 years
  • Any reason why, in the opinion of the investigator, the patient should not participate

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03317327

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Contact: Åse Bratland, M.D.-Ph.D. 4024 3735/2293 5942 ext +47
Contact: Jon Amund Kyte, M.D.-Ph.D 9756 9619/2293 4000 ext +47

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Oslo University Hospital Recruiting
Oslo, Norway
Contact: Åse Bratland, M.D.-Ph.D.    +474024 3735/+472293 5942   
Principal Investigator: Åse Bratland, M.D.-Ph.D.         
Sub-Investigator: Jon Amund Kyte, M.D.-Ph.D.         
Sponsors and Collaborators
Oslo University Hospital
Bristol-Myers Squibb
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Principal Investigator: Åse Bratland, m Oslo University Hospital
  Study Documents (Full-Text)

Documents provided by Åse Bratland, Oslo University Hospital:
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Responsible Party: Åse Bratland, Principal Investigator, Oslo University Hospital Identifier: NCT03317327    
Other Study ID Numbers: CA209-686_REPORT
First Posted: October 23, 2017    Key Record Dates
Last Update Posted: September 30, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Åse Bratland, Oslo University Hospital:
Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action