Head and Neck Squamous Cell Carcinoma (HNSCC)Phase 1NCT02764593
Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer
A Phase 1 study testing Nivolumab, Cisplatin and Cetuximab in people with Head and Neck Squamous Cell Carcinoma (HNSCC), run by RTOG Foundation, Inc. at 11 sites in United States.
Trial summary
This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma (HNSCC)
- What is being tested?
- Nivolumab, Cisplatin and Cetuximab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 11 sitesUnited States
- Study dates
- Jun 2016to 21 Feb 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx.
- Intermediate-risk group: Oropharynx cancer that is p16-positive by immunohistochemistry with smoking status > 10 Pack-years, stage T1-2N2b-N3 OR ≤ 10 pack-years, stage T4N0-N3 or T1-3N3.
- High-risk group: Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer, stage T1-2N2a-N3 or T3-4-N0-3 based on the following diagnostic workup:
- Mandatory submission of H\&E and p16 stained slides for central review of p16 staining is required for oropharyngeal patients and H\&E stained slide block (or punch biopsy of paraffin block) for PD-L1 expression analysis for all patients
- History/physical examination within 28 days prior to registration
- Examination by Radiation Oncologist, Medical Oncologist, and Ear, Nose, Throat (ENT) or Head \& Neck Surgeon within 28 days prior to registration
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- Fiberoptic exam with laryngopharyngoscopy within 28 days prior to registration
- Diagnostic quality, cross sectional imaging of the thorax within 28 days prior to registration; 18-F-FDG-PET/CT or conventional CT are acceptable.
- Diagnostic quality CT or MRI of neck, with contrast, within 28 days prior to registration; a 18-F-FDG-PET/CT of the neck only is acceptable as a substitute if the CT is of diagnostic quality and with IV contrast.
- Age ≥ 18 years
- The trial is open to both genders
Who cannot join
- Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease.
- Patients with oral cavity cancer are excluded from participation if resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist.
- Carcinoma of the neck of unknown primary site origin (even if p16-positive).
- Absence of RECIST, v. 1.1 defined measurable disease.
- Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible.
- Simultaneous primary cancers or separate bilateral primary tumor sites.
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- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
- Prior systemic chemotherapy for the study cancer.
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
- Patients with active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis.
- Use of systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled or topical steroids.
- Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL).
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Ohio State University
Columbus, Ohio, 43210
Inova Fairfax Hospital
Falls Church, Virginia, 22042
MD Anderson Cancer Center
Houston, Texas, 77030
University of Louisville
Louisville, Kentucky, 40202
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
University of Florida Cancer Center at Orlando Health
Orlando, Florida, 32806
Stanford Cancer Institute
Palo Alto, California, 94304
UPMC - Shadyside Hospital
Pittsburgh, Pennsylvania, 15232
Providence Portland Medical Center
Portland, Oregon, 97213
About this study
Official title: Safety Evaluations of Nivolumab (Anti-PD-1) Added To Chemotherapy (CRT) Platforms In Patients With Intermediate And High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma
This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.
- Keywords
- Head and Neck Squamous Cell Carcinoma, HNSCC, Nivolumab
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Anti-PD-1 targeted immunotherapy
CisplatinDrug
Also called Platinol
Anti-cancer alkylating agent
CetuximabDrug
Also called Erbitux
Epidermal Growth Factor Receptor (EGFR) antagonist
IMRTRadiation
Also called Intensity Modulated Radiation Therapy
High-precision radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (Nivolumab + Cisplatin) | Experimental | Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cisplatin will be given weekly. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. Receives: Drug: Nivolumab; Drug: Cisplatin; Radiation: IMRT |
| Arm 2 (Nivolumab + High-dose Cisplatin) | Experimental | Patients will receive Nivolumab via IV administration starting 14 days prior to IMRT, then Day 1 of IMRT and then every 21 days for 6 doses. Cisplatin will be given every 21 days for 3 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. Receives: Drug: Nivolumab; Drug: Cisplatin; Radiation: IMRT |
| Arm 3 (Nivolumab + Cetuximab) | Experimental | Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cetuximab will be given for 7 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. Receives: Drug: Nivolumab; Drug: Cetuximab; Radiation: IMRT |
| Arm 4 (Nivolumab + IMRT) | Experimental | Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. Receives: Drug: Nivolumab; Radiation: IMRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
A nivolumab attributable, dose-limiting toxicity (DLT) will be defined as follows:
- Any ≥ grade 3 adverse event (CTCAE, v. 4) that is related to nivolumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of > 2 weeks due to toxicity related to nivolumab; 3) Inability to complete radiotherapy due to toxicity related to nivolumab; 4) Inability to receive an adequate dose (≥ 70%) of cisplatin (Arm 1 and 2) or cetuximab (Arm 3) due to toxicity definitely related to nivolumab.
Measured: From the first dose of nivolumab to 28 days after the completion of radiation therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study startJun 2016
- Primary completion25 Sep 2018
- Study completion21 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck Squamous Cell Carcinoma (HNSCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- RTOG Foundation, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Maura Gillison, MD, PhD, Principal investigator, RTOG FoundationRobert Ferris, MD, PhD, Principal investigator, RTOG Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02764593
- Sponsor's protocol ID
- RTOG 3504
- Other IDs
- RF 3504, CA209-410
- Status last verified
- Nov 2022
- First submitted
- 4 May 2016
- Last updated
- 29 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Gillison ML, Ferris RL, Harris J, Colevas AD, Mell LK, Kong C, Jordan RC, Moore KL, Truong MT, Kirsch C, Chakravarti A, Blakaj DM, Clump DA, Ohr JP, Deeken JF, Gensheimer MF, Saba NF, Dorth JA, Rosenthal DI, Leidner RS, Kimple RJ, Machtay M, Curran WJ Jr, Torres-Saavedra P, Le QT. Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):847-860. doi: 10.1016/j.ijrobp.2022.10.008. Epub 2022 Oct 11.
PubMed 36228746
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety Evaluations of Nivolumab (Anti-PD-1) Added To Chemotherapy (CRT) Platforms In Patients With Intermediate And High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02764593
- Acronym / sponsor ID
- RTOG 3504
- Keywords
- Head and Neck Squamous Cell Carcinoma, HNSCC, Nivolumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- RTOG Foundation, Inc.University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jun 2016
- Primary completion
- 25 Sep 2018 (actual)
- Study completion
- 21 Feb 2022 (actual)
- First posted
- 6 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (Nivolumab + Cisplatin) | Experimental | Drug: Nivolumab, Drug: Cisplatin, Radiation: IMRTPatients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cisplatin will be given weekly. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. |
| Arm 2 (Nivolumab + High-dose Cisplatin) | Experimental | Drug: Nivolumab, Drug: Cisplatin, Radiation: IMRTPatients will receive Nivolumab via IV administration starting 14 days prior to IMRT, then Day 1 of IMRT and then every 21 days for 6 doses. Cisplatin will be given every 21 days for 3 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. |
| Arm 3 (Nivolumab + Cetuximab) | Experimental | Drug: Nivolumab, Drug: Cetuximab, Radiation: IMRTPatients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cetuximab will be given for 7 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. |
| Arm 4 (Nivolumab + IMRT) | Experimental | Drug: Nivolumab, Radiation: IMRTPatients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx.
- Intermediate-risk group: Oropharynx cancer that is p16-positive by immunohistochemistry with smoking status > 10 Pack-years, stage T1-2N2b-N3 OR ≤ 10 pack-years, stage T4N0-N3 or T1-3N3.
- High-risk group: Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer, stage T1-2N2a-N3 or T3-4-N0-3 based on the following diagnostic workup:
- Age ≥ 18 years
- The trial is open to both genders
Key exclusion criteria (12 listed)
- Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease.
- Patients with oral cavity cancer are excluded from participation if resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist.
- Carcinoma of the neck of unknown primary site origin (even if p16-positive).
- Absence of RECIST, v. 1.1 defined measurable disease.
- Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoAnti-PD-1 targeted immunotherapy | Drug | Arm 1 (Nivolumab + Cisplatin), Arm 2 (Nivolumab + High-dose Cisplatin), Arm 3 (Nivolumab + Cetuximab), Arm 4 (Nivolumab + IMRT) |
| CisplatinAlso: PlatinolAnti-cancer alkylating agent | Drug | Arm 1 (Nivolumab + Cisplatin), Arm 2 (Nivolumab + High-dose Cisplatin) |
| CetuximabAlso: ErbituxEpidermal Growth Factor Receptor (EGFR) antagonist | Drug | Arm 3 (Nivolumab + Cetuximab) |
| IMRTAlso: Intensity Modulated Radiation TherapyHigh-precision radiotherapy | Radiation | Arm 1 (Nivolumab + Cisplatin), Arm 2 (Nivolumab + High-dose Cisplatin), Arm 3 (Nivolumab + Cetuximab), Arm 4 (Nivolumab + IMRT) |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: From the first dose of nivolumab to 28 days after the completion of radiation therapy.
A nivolumab attributable, dose-limiting toxicity (DLT) will be defined as follows: 1) Any ≥ grade 3 adverse event (CTCAE, v. 4) that is related to nivolumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of > 2 weeks due to toxicity related to nivolumab; 3) Inability to complete radiotherapy due to toxicity related to nivolumab; 4) Inability to receive an adequate dose (≥ 70%) of cisplatin (Arm 1 and 2) or cetuximab (Arm 3) due to toxicity definitely related to nivolumab.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Derived from this study: PubMed 36228746Gillison ML, Ferris RL, Harris J, Colevas AD, Mell LK, Kong C, Jordan RC, Moore KL, Truong MT, Kirsch C, Chakravarti A, Blakaj DM, Clump DA, Ohr JP, Deeken JF, Gensheimer MF, Saba NF, Dorth JA, Rosenthal DI, Leidner RS, Kimple RJ, Machtay M, Curran WJ Jr, Torres-Saavedra P, Le QT. Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):847-860. doi: 10.1016/j.ijrobp.2022.10.008. Epub 2022 Oct 11.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maura Gillison, MD, PhD principal investigator
RTOG Foundation
Robert Ferris, MD, PhD principal investigator
RTOG Foundation
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab, Cisplatin and Cetuximab in people with Head and Neck Squamous Cell Carcinoma (HNSCC), run by RTOG Foundation, Inc. at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) (time frame: From the first dose of nivolumab to 28 days after the completion of radiation therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02764593, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2022.