Actively Recruiting
Two-cohort Study of Niraparib and Dostarlimab Plus (Chemo)RadIotherapy in Locally-Advanced Head and Neck Squamous Cell Carcinoma
Led by Grupo Español de Tratamiento de Tumores de Cabeza y Cuello · Updated on 2025-03-13
34
Participants Needed
5
Research Sites
277 weeks
Total Duration
On this page
Sponsors
G
Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
Lead Sponsor
G
GlaxoSmithKline
Collaborating Sponsor
AI-Summary
What this Trial Is About
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. 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. Concurrent phase (radiosensitization): patients will receive definitive radiotherapy (70Gy in 35 fractions) with concurrent cisplatin (Cohort A) or with concurrent niraparib (Cohort B). 3. Maintenance: Following radiotherapy, patients will receive adjuvant dostarlimab plus niraparib until week 48 (37 cycles) in both cohorts.
CONDITIONS
Official Title
Two-cohort Study of Niraparib and Dostarlimab Plus (Chemo)RadIotherapy in Locally-Advanced Head and Neck Squamous Cell Carcinoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Signed written and voluntary informed consent.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and study procedures.
- Age greater than 18 years, male or female.
- Histologically confirmed new diagnosis of non-metastatic squamous cell carcinoma of the head and neck, including Stage III HPV-related oropharyngeal carcinoma; Stage III, IVA, and IVB HPV-unrelated oropharyngeal, laryngeal, hypopharyngeal carcinomas; or unresectable Stage IVB oral cavity carcinoma.
- HPV-related oropharyngeal cancers must be confirmed by positive p16 immunohistochemical staining and HPV DNA testing.
- Evaluable tumor burden by CT or MRI based on RECIST 1.1.
- Newly obtained core or excisional tumor biopsy available for biomarker analysis.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Adequate organ function including specified blood counts and liver function.
- Specific criteria for Cohort A: creatinine clearance > 60 mL/min, no peripheral neuropathy > grade 2, no significant hearing loss/tinnitus ≥ grade 3, age 18-70 years, no significant cardiovascular disease.
- Specific criteria for Cohort B: unfit for cisplatin-based chemoradiotherapy due to creatinine clearance 30-60 mL/min, hearing loss/tinnitus ≥ grade 3, peripheral neuropathy > grade 2, or age > 70 years with acceptable G8 geriatric screening score.
- Evidence of post-menopausal status or negative pregnancy test for pre-menopausal women, with age-specific definitions for menopause.
You will not qualify if you...
- Early stage (I-II) head and neck cancers of any location.
- Resectable Stage III-IVA oral cavity carcinoma.
- Cancer outside oropharynx, larynx, hypopharynx, including nasopharyngeal, sinus, para-nasal, or unknown primary cancers.
- Current or prior other head and neck malignancies.
- Previous treatment for current head and neck cancer except diagnostic biopsy.
- Previous radiation overlapping the current treatment area.
- Inability to swallow niraparib capsules.
- Significant recent weight loss or low albumin levels without nutritional support.
- Active or uncontrolled bleeding requiring transfusions.
- Allergy or hypersensitivity to study drugs or excipients.
- Rare hereditary disorders affecting niraparib absorption.
- History of primary immunodeficiency, organ transplant requiring immunosuppression, or severe immune-related toxicities.
- Recent or active autoimmune or inflammatory disorders with specific exceptions.
- History of interstitial lung disease or pneumonitis requiring steroids.
- Concurrent chemotherapy, biologic, immunologic, or hormonal cancer therapies.
- Recent use of immunosuppressive medications except specified exceptions.
- Recent autoimmune diseases within 2 years with specific exceptions.
- History of stroke or transient ischemic attack within 6 months.
- Uncontrolled hypertension or certain cardiac abnormalities.
- Use of medications causing prolonged QT that cannot be changed.
- History of organ transplant requiring immunosuppression.
- Prior history of posterior reversible encephalopathy syndrome.
- HIV positive status.
- Active hepatitis B or C infection without successful treatment.
- Pregnant or breastfeeding women.
- Uncontrolled intercurrent illness or psychiatric/social conditions limiting compliance.
- Prior treatment with PARP, PD-L1, or CTLA-4 inhibitors.
- History of other active malignancies within specified time frames.
- Major surgery within 28 days prior to study treatment.
- Prior severe immune-related adverse events or unresolved toxicities.
- Malabsorption problems affecting drug absorption.
- History or risk of myelodysplastic syndrome or acute myeloid leukemia based on cytogenetic testing.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 5 locations
1
Institut Catalá d'Oncologia (ICO) BADALONA
Badalona, Catalonia, Spain, 08916
Actively Recruiting
2
Hospital Universitario Valle Hebron
Barcelona, Catalonia, Spain, 08035
Actively Recruiting
3
Hospital Clinic de Barcelona
Barcelona, Catalonia, Spain, 08036
Actively Recruiting
4
Institut Catalá d'Oncologia (ICO) Hospitalet
L'Hospitalet de Llobregat, Catalonia, Spain, 08908
Actively Recruiting
5
Complejo Hospitalario de Navarra
Pamplona, Navarre, Spain, 31008
Actively Recruiting
Research Team
F
Federico Nepote
CONTACT
M
Marisa Duran; Senior clinical research project manager (TTCC)
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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