REirradiation and Programmed Cell Death Protein 1 (PD-1) Blockade On Recurrent Squamous Cell Head and Neck Tumors (REPORT)
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|ClinicalTrials.gov Identifier: NCT03317327|
Recruitment Status : Recruiting
First Posted : October 23, 2017
Last Update Posted : November 14, 2018
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Exploratory|
|Masking:||None (Open Label)|
|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|
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.
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
- 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) ]
- 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
- Objective response rate (ORR) [ Time Frame: 3 years ]defined as the proportion of patients with an objective tumor response
- Overall survival (OS) [ Time Frame: 5 years ]defined as the time from the date of inclusion to the date of death from any cause
- Duration of response (DOR) [ Time Frame: 3 years ]among patients with an objective response
- Durable response rate (DRR) [ Time Frame: 3 years ]defined as the proportion of patients with an objective tumor response lasting at least 6 months
- Immunological response [ Time Frame: 3 years ]as assessed by gene profiling, immunohistochemistry, T cell assays, characterization of cell suspensions from tumor and peripheral blood
- tumor evolution [ Time Frame: 3 years ]as assessed by gene profiling, immunohistochemistry, characterization of cell suspensions from tumor and peripheral blood
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 ClinicalTrials.gov identifier (NCT number): NCT03317327
|Contact: Åse Bratland, M.D.-Ph.D.||4024 3735/2293 5942 ext +47||BRT@ous-hf.no|
|Contact: Jon Amund Kyte, M.D.-Ph.D||9756 9619/2293 4000 ext +47||Jon.email@example.com|
|Oslo University Hospital||Recruiting|
|Contact: Åse Bratland, M.D.-Ph.D. 4024 3735/2293 5942 BRT@ous-hf.no|
|Principal Investigator: Åse Bratland, M.D.-Ph.D.|
|Sub-Investigator: Jon Amund Kyte, M.D.-Ph.D.|
|Principal Investigator:||Åse Bratland, m||Oslo University Hospital|