Nivolumab Plus Weekly Carboplatin and Paclitaxel as Induction in Resectable Locally Advanced Head and Neck Cancer
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- Name Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma
- Sponsor
- Sidney Kimmel Cancer Center at Thomas Jefferson University
- Enrollment
- 34
- Locations
- 3
- Primary Endpoint
- Pathologic Complete Response Rate
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This phase II trial studies how well nivolumab, carboplatin, and paclitaxel work in treating patients with stage III-IV head and neck squamous cell carcinoma that can be removed by surgery. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab, carboplatin, and paclitaxel may work better in treating patients with head and neck squamous cell carcinoma.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate pathologic complete response (pCR) at the primary site in patients with newly diagnosed and untreated stage III-IVA squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, larynx, and hypopharynx with nivolumab, paclitaxel and carboplatin in addition to standard chemotherapy. SECONDARY OBJECTIVES: I. Safety. II. Complete pathologic response at all sites of disease. III. Major pathologic response rate at primary site. IV. Overall clinical response rate. V. Clinical complete response rate. VI. 1 year progression-free survival (PFS). VII. Overall survival. TERTIARY OBJECTIVES: I. To explore whether PDL1 expression is associated with treatment response. II. To explore whether there is a net change in the Th1/Th2 ratio (IFN-gamma, IL-4, IL10, etc.) or cell subset frequencies (M2 monocytes, myeloid-derived suppressor cells, etc.) within a patient's peripheral blood either at baseline or in response to treatment is associated with treatment response. III. To explore whether exosomes or other immune related serum biomarkers change after combination therapy. IV. To explore the predictive value of serial cell free deoxyribonucleic acid (DNA) levels and response.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be 18 years of age and older.
- •Pathologically confirmed SCCHN, not previously treated, with a plan to undergo surgery
- •Patients who have stage III-IV disease without distant metastases (M0) of 1) oral cavity, 2) larynx, 3) hypopharynx 4) oropharynx (human papillomavirus \[HPV\] neg) using American Joint Committee on Cancer (AJCC) 8th edition
- •Patients who have oropharyngeal cancer that HPV positive, stage II-III disease without distant metastases (M0) using AJCC 8th edition
- •All patients with oropharyngeal SCCHN must be tested for HPV (by p16 and/or HPV in situ hybridization \[ISH\] or polymerase chain reaction \[PCR\])
- •Patients must be evaluated by a head and neck surgeon and be deemed surgically resectable at baseline
- •Tumor sample must be available for HPV p16 and PD-L1 testing and if oropharyngeal, must be tested for HPV p16
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •While blood cells 2000/ul or more
- •Absolute neutrophil count 1500/ul or more
Exclusion Criteria
- •Primary nasopharyngeal carcinoma
- •Patients who have participated in a study with an investigational agent or device within 2 weeks of initiation of treatment
- •Any prior radiotherapy to the neck
- •Any prior treatment for SCCHN
- •Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- •Any history of a sever hypersensitivity reaction to any monoclonal antibody
- •Any history of allergy to the study drug components
- •Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy; patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post-diagnosis
- •Any diagnosis of immunodeficiency or current immunosuppressive therapy including \>10mg/day of prednisone within 14 days of enrollment is not permitted (excludes emergency transient steroid use at discretion of the treating physician).
- •Patients that have an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids (\> 10 mg daily prednisone equivalents) or immunosuppressive agents. Subjects with vitiligo, type I diabetes mellitus, or resolved childhood asthma/atopy would be an exception to this rule. Inhaled or topical steroids, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
Arms & Interventions
Treatment (nivolumab, paclitaxel, carboplatin)
Patients receive nivolumab IV over at least 30 minutes on day 1, paclitaxel IV on days 1 and 8, and carboplatin IV on days 1 and 8. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Treatment (nivolumab, paclitaxel, carboplatin)
Patients receive nivolumab IV over at least 30 minutes on day 1, paclitaxel IV on days 1 and 8, and carboplatin IV on days 1 and 8. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin
Treatment (nivolumab, paclitaxel, carboplatin)
Patients receive nivolumab IV over at least 30 minutes on day 1, paclitaxel IV on days 1 and 8, and carboplatin IV on days 1 and 8. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Pathologic Complete Response Rate
Time Frame: Up to 26 months
The primary objective of the study is to estimate the rate of pathologic complete response (pCR) at the primary site, defined as the absence of any residual invasive cancer on H\&E evaluation of the resected specimen and all sampled ipsilateral lymph nodes, in patients with newly diagnosed and untreated Stage III-IVA SCCHN of the oral cavity, Oropharynx, Larynx, and Hypopharynx treated with standard neoadjuvant chemotherapy plus Nivolumab, paclitaxel, and carboplatin. Pathologic complete response rate and its associated score 95% confidence interval will be estimated.
Secondary Outcomes
- Number of Patients Who Achieved Major Pathologic Response (Defined as 10% or Less Residual Viable Tumor)(Up to 26 months)