Screening Trial of Nivolumab With Image Guided, Stereotactic Body Radiotherapy (SBRT) Versus Nivolumab Alone in Patients With Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

NCT02684253 | Completed Phase 2 Results

• 1 other identifier: 15-253
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 6

Brief Summary

Nivolumab is an antibody (a type of human protein) that is designed to boost your body's immune system. It does this by allowing immune cells to grow and fight the cancer. Nivolumab has been approved by the FDA for the treatment of melanoma (a form of skin cancer) and lung cancer. It is currently under study for the treatment of head and neck squamous cell cancer.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

Nivolumab; Stereotactic Body Radiotherapy (SBRT); 15-253

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  96 weeks

Study Arms (2)

Nivolumab 3mg/kg IV every 2 weeks

EXPERIMENTAL

Nivolumab 3mg/kg IV every 2 weeks

Drug: Nivolumab

Stereotactic Body Radiotherapy & Nivolumab

EXPERIMENTAL

Image Guided, Stereotactic Body Radiotherapy (27 Gy over 3 fractions given every other day) to a single lesion to start by study day 14 (study day 1 is day of first dose of Nivolumab). Nivolumab 3mg/kg IV starting day 1 and then every 2 weeks thereafter. Treatment with Nivolumab will continue until progression or unacceptable toxicity.

Drug: Nivolumab; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

Nivolumab DRUG

Nivolumab 3mg/kg IV every 2 weeks; Stereotactic Body Radiotherapy & Nivolumab

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Stereotactic Body Radiotherapy & Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Written Informed Consent
• Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study obligations.
• Target Population
• Males and females ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Histologically confirmed metastatic HNSCC, including nasopharynx WHO Type I-III histologies; patients can have simultaneous loco-regional disease. Central biopsy review at MSKCC is not required.
• Subjects must have at least two lesions:
• At least one lesion must be safely amenable to irradiation and likely to meet criteria delineated in Section 9.2.1 in the judgment of the treating radiation oncologist. This can be a lesion that was previously irradiated as long as prior radiation was at least 6 months prior to projected first fraction of SBRT and as long as reirradiation dose constraints as outlined in appendix are being met.
• A separate, not-to-be-irradiated lesion measurable by CT or MRI per RECIST 1.1 criteria.
• A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or a minimum of 3 unstained slides of tumor sample obtained via excisional, incisional, or core needle biopsy from a metastatic or loco-regionally recurrent lesion. A new baseline biopsy does not need to be obtained for study purposes. If 3 unstained are unavailable from a metastatic or loco-regionally recurrent lesion, with permission of the PI, FFPE tumor tissue from the primary disease site at the time of original diagnosis is acceptable.
• For oropharynx or nasopharynx primary lesions, documentation of viral status is required (e.g. high risk HPV sub-type PCR, p16 IHC, HPV ISH, EBER, etc). Tests done on primary tumor specimens from date of initial diagnosis at outside institutions are sufficient to meet this criterion
• Prior palliative or curative radiotherapy must be completed at least 14 days prior to randomization.
• Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses \>10mg/day prednisone or equivalent) must be discontinued at least 14 days prior to Nivolumab administration.
• Screening laboratory values must meet the following criteria (using CTCAE v4.0) and should be obtained within 28 days prior to randomization:

You may not qualify if:

• Target Disease Exceptions
• Active brain metastases (untreated brain metastases or growth on imaging as defined below) or leptomeningeal disease are not allowed. Subjects with brain metastases are eligible if these have been treated and there is no MRI (or CT if MRI contraindicated) evidence of progression for at least 8 weeks after treatment for these metastases is complete and within 28 days prior to first study treatment.
• Histologically confirmed non-squamous histologies are not allowed; an exception is made for WHO Type I-III nasopharynx histologies.
• Medical History and Concurrent Diseases:
• Any medical disorder that, in the opinion of the investigator, might increase the risk associated with study participation or interferes with the interpretation of study results.
• Prior active malignancy within the previous 3 years except for locally curable cancers such as basal or squamous skin cancer, superficial bladder, low risk prostate cancer, breast, or cervix cancer. If other prior malignancy was active within prior 3 years, enrollment requires approval of a principal investigator.
• Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration should be excluded. Inhaled or topical steroids and adrenal replacement doses \>10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• As there is potential for hepatic toxicity with Nivolumab, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with Nivolumab-containing regimen.
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
• NB-patients who have received prior anti-CTLA-4 antibody therapy are eligible assuming such therapy was discontinued within 28 days of enrollment.
• Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 14 days of randomization.
• Physical and Laboratory Test Findings
• Positive test for hepatitis B virus surface antigen or hepatitis C virus ribonucleic acid indicating acute or chronic infection.
• Known history of testing positive for HIV or known AIDS.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (6)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Related Publications (1)

• McBride S, Sherman E, Tsai CJ, Baxi S, Aghalar J, Eng J, Zhi WI, McFarland D, Michel LS, Young R, Lefkowitz R, Spielsinger D, Zhang Z, Flynn J, Dunn L, Ho A, Riaz N, Pfister D, Lee N. Randomized Phase II Trial of Nivolumab With Stereotactic Body Radiotherapy Versus Nivolumab Alone in Metastatic Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2021 Jan 1;39(1):30-37. doi: 10.1200/JCO.20.00290. Epub 2020 Aug 21.

  PMID: 32822275 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Nivolumab; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Sean McBride, MD, MPH
• Organization: Memorial Sloan Kettering Cancer Center

mcbrides@mskcc.org

646-608-2450

Study Officials

• Sean McBride, MD, MPH

  Memorial Sloan Kettering Cancer

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2016
• First Posted: February 17, 2016
• Study Start: February 11, 2016
• Primary Completion: January 22, 2021
• Study Completion: January 22, 2021
• Last Updated: March 10, 2022
• Results First Posted: March 10, 2022

Record last verified: 2021-01

Locations

US (6)