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REirradiation and Programmed Cell Death Protein 1 (PD-1) Blockade On Recurrent Squamous Cell Head and Neck Tumors (REPORT)

Primary Purpose

Head and Neck Squamous Cell Carcinoma

Status

Recruiting

Phase

Phase 1

Locations

Norway

Study Type

Interventional

Intervention

Nivolumab

Radiotherapy (RT)

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring HNSCC, Nivolumab, immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Oslo University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nivolumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence, nature, and severity of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Secondary Outcome Measures

Progression-free survival (PFS)

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)

defined as the proportion of patients with an objective tumor response

Overall survival (OS)

defined as the time from the date of inclusion to the date of death from any cause

Duration of response (DOR)

among patients with an objective response

Durable response rate (DRR)

defined as the proportion of patients with an objective tumor response lasting at least 6 months

Full Information

NCT ID

NCT03317327

First Posted

September 25, 2017

Last Updated

September 26, 2019

Sponsor

Oslo University Hospital

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT03317327

Brief Title

REirradiation and Programmed Cell Death Protein 1 (PD-1) Blockade On Recurrent Squamous Cell Head and Neck Tumors

Acronym

REPORT

Official Title

REPORT; REirradiation and PD-1 Blockade On Recurrent Squamous Cell Head and Neck Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Recruiting

Study Start Date

September 9, 2017 (Actual)

Primary Completion Date

November 2, 2023 (Anticipated)

Study Completion Date

November 2, 2040 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oslo University Hospital

Collaborators

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Head and Neck Squamous Cell Carcinoma

Keywords

HNSCC, Nivolumab, immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Exploratory

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nivolumab

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

Opdivo

Intervention Description

Nivolumab is a humanized antibody used in cancer immunotherapy.

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy (RT)

Intervention Description

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 Measure Information:

Title

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 Measure Information:

Title

Progression-free survival (PFS)

Description

defined as the time from inclusion to the time of radiographic progression (as assessed by RECIST) or death from any cause during the study

Time Frame

After 12 months

Title

Objective response rate (ORR)

Description

defined as the proportion of patients with an objective tumor response

Time Frame

3 years

Title

Overall survival (OS)

Description

defined as the time from the date of inclusion to the date of death from any cause

Time Frame

5 years

Title

Duration of response (DOR)

Description

among patients with an objective response

Time Frame

3 years

Title

Durable response rate (DRR)

Description

defined as the proportion of patients with an objective tumor response lasting at least 6 months

Time Frame

3 years

Other Pre-specified Outcome Measures:

Title

Immunological response

Description

as assessed by gene profiling, immunohistochemistry, T cell assays, characterization of cell suspensions from tumor and peripheral blood

Time Frame

3 years

Title

tumor evolution

Description

as assessed by gene profiling, immunohistochemistry, characterization of cell suspensions from tumor and peripheral blood

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Åse Bratland, M.D.-Ph.D.

Phone

4024 3735/2293 5942

Ext

+47

BRT@ous-hf.no

First Name & Middle Initial & Last Name or Official Title & Degree

Jon Amund Kyte, M.D.-Ph.D

Phone

9756 9619/2293 4000

Ext

+47

Jon.amund.kyte@rr-research.no

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Åse Bratland, m

Organizational Affiliation

Oslo University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Oslo University Hospital

City

Oslo

Country

Norway

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Åse Bratland, M.D.-Ph.D.

Phone

+474024 3735/+472293 5942

BRT@ous-hf.no

First Name & Middle Initial & Last Name & Degree

Åse Bratland, M.D.-Ph.D.

First Name & Middle Initial & Last Name & Degree

Jon Amund Kyte, M.D.-Ph.D.

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

REirradiation and Programmed Cell Death Protein 1 (PD-1) Blockade On Recurrent Squamous Cell Head and Neck Tumors

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