Two-cohort Study of Niraparib and Dostarlimab Plus (Chemo)RadIotherapy in Locally-Advanced Head and Neck Squamous Cell Carcinoma

NCT05784012 | Recruiting Phase 1

• 2 other identifiers: TTCC-2022-01-RADIAN2023-000183-65
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 5

Brief Summary

Multi-center, open-label, non-randomized, non-comparative two-cohort study for patients with locally-advanced squamous cell carcinoma arising from the larynx, hypopharynx, oropharynx (Stage III, IVA and IVB according to 8th TNM/AJCC ed.) and oral cavity (unresectable, stage IVB according to 8th TNM/ American Joint Committee on Cancer (AJCC) ed.) who are candidates for definitive radiotherapy plus cisplatin (Cohort A) or as single-modality (in cisplatin unfit patient population) (Cohort B) and will receive dostarlimab and niraparib in combination pre-, during and post- radiation. Study has three parts:

1. 1.Neoadjuvant phase (immune-conditioning phase): patients will receive 1 dose of dostarlimab + niraparib from day -14 prior to radiotherapy (up to 48h prior to radiotherapy (RT) in Cohort A and until RT in Cohort B).
2. 2.Concurrent phase (radiosensitization): patients will receive definitive radiotherapy (70Gy in 35 fractions) with concurrent cisplatin (Cohort A) or with concurrent niraparib (Cohort B).
3. 3.Maintenance: Following radiotherapy, patients will receive adjuvant dostarlimab plus niraparib until week 48 (37 cycles) in both cohorts.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

non-metastatic; Oropharyngeal carcinoma; Laryngeal or hypopharyngeal carcinomas; Oral carcinoma; squamous cell carcinoma; radiotherapy; antiPD-1; PARP inhibitor

Outcome Measures

Primary Outcomes (1)

• 1-year disease free survival

  Disease-free survival (DFS) is defined as the time from the date of study treatment initiation to the date of first record of any of the following events: Investigator determined: Locoregional progression or recurrence. Distant metastasis. Neck dissection or surgery performed for clinical or radiological disease progression (RECIST 1.1) \> 20 weeks from the end of radiation therapy with tumor present on final pathology. Death due to any cause. Patients not presenting any of the previous events will be censored at the date of last assessment.

  1 year after the start of the study treatment

Secondary Outcomes (6)

• Disease control rate

  Throughout the study period, approximately 36 months

• Locoregional control

  Throughout the study period, approximately 36 months

• Distant control

  Throughout the study period, approximately 36 months

• Event-free survival

  Throughout the study period, approximately 36 months

• Overall survival

  Throughout the study period, approximately 36 months

Study Arms (2)

Cohort A

EXPERIMENTAL

Three stages: Neoadjuvant: single dose of dostarlimab 500 mg intravenously on day -21 and niraparib 200 or 300 mg orally once daily starting on day -14 until 48 hours prior to the start of definitive radiotherapy (day 0). Concurrent: definitive radiotherapy (70 Gy in 35 fractions, 1 fraction per day from Monday to Friday) with concurrent Cisplatin at a dose of 100 mg/m2 intravenously on day 1 of week 1, week 4 and week 7. Maintenance: dostarlimab to be administered as a single infusion dose of 500 mg on day 1 every 21 days from week 11 to week 48. Niraparib will be given once daily at a dose of 200 or 300 mg in cycles of 21 days.

Drug: Dostarlimab; Drug: cisplatin plus radiotherapy; Drug: Niraparib

Cohort B

EXPERIMENTAL

Three stages: Neoadjuvant: single dose of dostarlimab 500 mg intravenously on day -21 and niraparib 200 or 300 mg orally once daily starting on day -14 until the start of definitive radiotherapy (day 0). Concurrent: definitive radiotherapy (70 Gy in 35 fractions, 1 fraction per day from Monday to Friday). Niraparib is to be given once daily on a continous basis (200 to 300 mg), from w1 d1 until end of w10 in cycles of 21 days. Maintenance: dostarlimab to be administered as a single infusion dose of 500 mg on day 1 every 21 days from week 11 to week 48. Niraparib will be given once daily on a continous basis at a dose of 200 or 300 mg in cycles of 21 days.

Drug: Dostarlimab; Drug: Niraparib

Interventions

Dostarlimab DRUG

Dostarlimab 500 mg IV every 21 days in neoadjuvant and adjuvant stage.

Cohort A; Cohort B

Niraparib DRUG

Niraparib 200 or 300mg orally administered QD in neoadjuvant, concurrent with radiotherapy and adjuvant stage until completing week 48.

Cohort B

cisplatin plus radiotherapy DRUG

In the concurrent phase

Cohort A

Eligibility Criteria

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

You may qualify if:

• Informed consent
• Signed written and voluntary informed consent.
• Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
• Age \> 18 years, male or female.
• Disease characteristics
• Have histologically confirmed new diagnosis of non-metastatic squamous cell carcinoma as assessed by the Investigator based on baseline imaging and clinical assessment that is either:
• Stage III HPV-related oropharyngeal carcinoma OR
• Stage III, IVA and IVB HPV-unrelated oropharyngeal, laryngeal or hypopharyngeal carcinomas. Stage IVB oral cavity squamous cell carcinomas may be eligible upon consultation with Sponsor if considered unresectable as per treating surgeon and multidisciplinary tumor board.
• According to UICC/AJCC 8th Edition staging
• Human papillomavirus (HPV)-relatedness in oropharyngeal primaries must be determined by positive p16 immunohistochemical staining on any tumor specimens and, if positive, confirmed by human papilloma virus (HPV) DNA testing by in situ hybridisation (ISH) or polymerase chain reaction (PCR). Positive p16 expression is defined as strong and diffuse nuclear and cytoplasmic staining in 70 % or more of the tumor cells. Local testing is acceptable.
• Have an evaluable tumor burden assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) based on RECIST 1.1 as assessed by the local site investigator/radiology.
• Have provided newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for central biomarker analysis (fine needle aspirate (FNA) is not adequate).
• Repeat samples may be required if adequate tissue is not provided. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides.
• Patient characteristics
• Eastern cooperative oncology group (ECOG) performance status 0-1.

You may not qualify if:

• Early stages, defined as stage I-II according to Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) 8th Edition staging in any localization, and including HPV-related and non-related.
• Stage III-IVA oral cavity carcinoma considered resectable as per treating surgeon and/or multidisciplinary tumor board.
• Has cancer outside of the oropharynx, larynx, and hypopharynx, nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck carcinoma (HNC).
• Current history of other head and neck malignancies.
• Any previous treatment for current head and neck cancer including systemic therapy, radiotherapy and/or surgery (except for a diagnostic biopsy) and no major surgery within 28 days prior to study treatment initiation.
• Any previous radiation to the head and neck region that would result in overlap of fields for the current study.
• Any previous radiotherapy treatment encompassing \> 20 % of the bone marrow within 2 weeks or any radiotherapy within 1 week prior to Day 1 of protocol therapy.
• Patients unable to swallow niraparib capsules/tablets.
• Documented weight loss of \>10 % during the last 4 weeks prior to study treatment initiation (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin \< 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before study treatment initiation.
• Active gastrointestinal bleeding, or any other uncontrolled bleeding requiring more than 2 red blood cell transfusions or 4 units of packed red blood cells within 4 weeks prior to study treatment initiation.
• History of allergic or hypersensitivity reactions to any study drug or their excipients.
• Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take niraparib.
• History of primary immunodeficiency, history of allogeneic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of study treatment initiation or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease (controlled by diet alone) or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: vitiligo or alopecia; Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years); Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement. Any chronic skin condition that does not require systemic therapy.
• History of interstitial lung disease e.g. pneumonitis requiring steroids (any dose) or immunomodulatory treatment within 90 days of planned start of the study therapy; or pulmonary fibrosis or evidence of pneumonitis on baseline CT scan.

Sponsors & Collaborators

• Grupo Español de Tratamiento de Tumores de Cabeza y Cuello: lead
• GlaxoSmithKline: collaborator
• MFAR: collaborator

Study Sites (5)

Institut Catalá d'Oncologia (ICO) BADALONA

Badalona, Catalonia, 08916, Spain

RECRUITING

Hospital Universitario Valle Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Catalonia, 08036, Spain

RECRUITING

Institut Catalá d'Oncologia (ICO) Hospitalet

L'Hospitalet de Llobregat, Catalonia, 08908, Spain

RECRUITING

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Laryngeal Diseases; Mouth Neoplasms; Carcinoma, Squamous Cell

Interventions

dostarlimab; niraparib; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Respiratory Tract Diseases; Mouth Diseases; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Marc Oliva, M.D.

  Institut Català D´Oncologia (ICO) Hospitalet de Llobregat

  STUDY CHAIR

• Ricard Mesia, M.D. Ph.D.

  Institut Català d''Oncologia (ICO) Badalona

  STUDY CHAIR

Central Study Contacts

Federico Nepote

CONTACT

0034934344412; investigacion@mfar.net

Marisa Duran; Senior clinical research project manager (TTCC)

CONTACT

0034690756714; mduran@ttccgrupo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two cohorts: Cohort A: Patients who are candidates for definitive radiotherapy plus cisplatin (eligible for platinum). Cohort B: Patients who are ineligible for cisplatin.

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 24, 2023
• Study Start: November 8, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)