Induction TPN Followed by Nivolumab With Radiation in Locoregionally Advanced Laryngeal and Hypopharyngeal Cancer

NCT03894891 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-652
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

This research is being performed to treat patient for head and neck cancer patients who have not received prior chemotherapy.

Conditions

Head and Neck Cancer

Keywords

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Median Laryngectomy-free Survival (LFS)

  LFS defined as time from study registration to earlier of surgical removal of larynx and/or hypopharynx, or death due to any cause. Participants alive with intact larynx and hypopharynx are censored at date of last disease evaluation. Given limited sample size and zero events, the Kaplan-Meier method was not used for estimate of LFS.

  Disease was assessed following the completion of 2-3 cycles of induction TPN, 10-12 weeks after the completion of immunoradiotherapy or surgery and every 3 months until disease progression (PD). Participants were followed up to 18.9 months.

Secondary Outcomes (6)

• Best Radiologic Response

  Disease evaluation following the completion of the induction phase of treatment on cycle 3 day 43-63.

• Median Censoring Time for Overall Survival (OS)

  Participants were observed for OS up to 23.2 months.

• Median Laryngo-esophageal Dysfunction-free Survival (LEDFS)

  Disease was assessed following the completion of 2-3 cycles of induction TPN, 10-12 weeks after the completion of immunoradiotherapy or surgery and every 3 months until disease progression (PD). Participants were observed for LEDFS up to 18.9 months.

• EORTC QLQ-C30 Change in Emotional Functional Score From Baseline to Post IMRT+Nivolumab

  At baseline and post IMRT+Nivolumab approximately 22 weeks from start of induction treatment.

• Number of Participants With Grade 3-5 Treatment-related Adverse Events

  AEs were evaluated up to 9.6 months, representing maximum treatment duration for this study cohort.

Study Arms (1)

Induction Docetaxel (T)+Cisplatin (P)+Nivolumab (N) then Radioimmunotherapy (IMRT+N) then adjuvant N

EXPERIMENTAL

Participants received 3 cycles of induction with docetaxel, cisplatin and nivolumab (TPN) every 3 weeks (or 21 days): docetaxel 75 mg/m2 IV day 1, cisplatin 100 mg/m2 IV day 1, and nivolumab 240 mg IV flat dose day 1. Induction was followed by clinical and radiologic assessment of response. Participants without partial response or better based on RECIST 1.1 were offered salvage laryngectomy and/or pharyngectomy. Participants with partial or complete response per RECIST 1.1 proceeded with immunoradiotherapy concurrently with nivolumab. Intensity-modulated radiotherapy (IMRT) was preferred and proton beam radiotherapy not permitted. Nivolumab 240 mg IV flat dose day 1 was repeated every 2 weeks concurrently with IMRT (for a total of 3-4 doses). Participants then received adjuvant nivolumab (480 mg IV flat dose day 1) every 4 weeks within 3-8 weeks from the last day of IMRT for up to 6 cycles or until disease progression or recurrence.

Drug: Nivolumab; Drug: Cisplatin; Drug: Docetaxel; Radiation: Intensity-modulated radiotherapy

Interventions

Nivolumab DRUG

Nivolumab is a type of immunotherapy.

Also known as: OPDIVO®

Induction Docetaxel (T)+Cisplatin (P)+Nivolumab (N) then Radioimmunotherapy (IMRT+N) then adjuvant N

Cisplatin DRUG

Cisplatin is a chemotherapy drug.

Also known as: Platinol

Induction Docetaxel (T)+Cisplatin (P)+Nivolumab (N) then Radioimmunotherapy (IMRT+N) then adjuvant N

Docetaxel DRUG

Docetaxel is a chemotherapy drug.

Also known as: Taxotere

Induction Docetaxel (T)+Cisplatin (P)+Nivolumab (N) then Radioimmunotherapy (IMRT+N) then adjuvant N

Intensity-modulated radiotherapy RADIATION

IMRT is definitive treatment for head and neck cancer.

Also known as: IMRT

Induction Docetaxel (T)+Cisplatin (P)+Nivolumab (N) then Radioimmunotherapy (IMRT+N) then adjuvant N

Eligibility Criteria

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

You may qualify if:

• Subject must have histologically or cytologically confirmed, resectable or unresectable, Stage III or Stage IV locoregionally advanced squamous cell carcinoma of the larynx or hypopharynx, as defined by 2017 American Joint Committee on Cancer (AJCC), 8th edition
• Willing to provide tissue from diagnostic biopsy and blood samples before, during, and after treatment
• Any smoking history is permitted
• Patients must have HPV negative disease. Those patients with a supraglottic primary are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV PCR or ISH testing to rule out oropharyngeal origin with laryngeal extension
• Age 18 years or older
• ECOG performance status ≤ 1 (Karnofsky ≥ 80%, see Appendix A)
• Participant must have normal organ and marrow function as defined below within 21 days prior to study registration:
• leukocytes ≥3,000/mcL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤2.0 g/dL
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Existing severe autoimmune conditions (at the discretion of the treating physician). Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded. Short-term corticosteroid dosing is permitted (i.e. dexamethasone for chemotherapy-induced nausea prevention during induction chemotherapy) as long as steroids are discontinued within 1 week (7 days) of receiving the first dose of nivolumab during the induction phase of treatment.
• Subject who has had prior chemotherapy for head and neck cancer and/or radiotherapy to the head and neck.
• Subject who has been treated with immunotherapy. This includes prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative).
• Known non-infectious pneumonitis or any history of interstitial lung disease.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and low-risk prostate adenocarcinoma being managed with active surveillance. A history of another separate malignancy in remission without evidence of active disease in the last 5 years is permitted.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Winship Cancer Institute

Atlanta, Georgia, 30308, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

The Tisch Cancer Institute

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Nivolumab; Cisplatin; Docetaxel; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Limitations and Caveats

This study terminated early due to weak accrual and therefore no inference is possible.

Results Point of Contact

• Title: Robert Haddad, MD
• Organization: Dana-Farber Cancer Institute

Robert_Haddad@dfci.harvard.edu

617.632.3090

Study Officials

• Robert Haddad, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: March 29, 2019
• Study Start: June 11, 2019
• Primary Completion: October 31, 2022
• Study Completion: December 16, 2022
• Last Updated: December 20, 2023
• Results First Posted: December 20, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (4)