Oropharynx Cancer
Conditions
Brief summary
The majority of head and neck cancer patients do not respond to immunotherapies, and clinical responses are often not durable. However, targeting tumors with stereotactic radiation in combination with immunotherapy while sparing draining lymphatics enhances anticancer immunity, resulting in dramatic response in HPV (Human Papilloma Virus) virus related cancers of the throat. This trial will leverage targeted tumor radiation and immunotherapy in advance of standard surgical therapy to improve the response of HPV (Human Papilloma Virus) throat cancer to radiation and immunotherapy.
Detailed description
This is a prospective, multi-center, open-label, one-arm, two-stage, Phase II study to evaluate the efficacy of neoadjuvant immunoradiotherapy (NIRT) in patients with stage I HPVOPC (Human Papilloma Virus Oropharynx Cancer) amenable to surgical resection, including AJCC (American Joint Committee on Cancer) VIII T1-2N1M0 HPVOPC (Human Papilloma Virus Oropharynx Cancer) and excluding patients with solitary lymph nodes less than 3 cm. A Simon's two-stage optimal design is used for this study. We will test the hypothesis that neoadjuvant stereotactic tumor targeting radiation along with CD47 inhibition (evorpacept) and PD-1 inhibition (pembrolizumab) provides pathologic response compared to current standard of care rates of locoregional control.
Interventions
DRUGEvorpacept
After stereotactic radiation to primary tumor and neck on week 1 of study, Evorpacept 45 mg/kg is administered by IV infusion every three weeks starting on Week 2, Day 1 of study for a total two 21-day cycles (6 weeks)
Sponsors
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A phase II clinical trial for AJCC (American Joint Committee on Cancer) VIII Stage I T1-2N1M0 HPVOPC, including patients amenable to surgical resection, excluding patients with solitary lymph nodes less than 3 cm who are amenable to surgical therapy alone. Stereotactic radiation therapy (SBRT (8GyX3)) will be delivered to gross tumor volume (GTV) +3mm, followed by Pembrolizumab 200 mg IV and Evorpacept 45 mg/kg IV every three weeks x 2 cycles followed by surgical resection of primary tumor and neck dissection. The primary endpoint is pathologic response compared to historical standard of care rates of locoregional control, and secondary endpoints are clinical response, survival, and safety and toxicity.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of Stage I T1-2N1M0 HPVOPC (Human Papilloma Virus Oropharynx Cancer) * Amenable to surgical resection * Are able to safely receive neoadjuvant radiation and Evorpacept/Pembrolizumab
Exclusion criteria
• Patients with solitary lymph nodes less than 3 cm
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response | week 7-10 | Pathologic response is determined when surgery is performed at week 7-10 of study |
| Major pathologic response | week 7-10 | Major pathologic response is defined as \<10% viable tumor cells in the resection specimen) after surgical resection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall survival | 3 years | survival will be determined based on intent to treat analysis at conclusion of study after 3 years |
| disease free survival | 3 years | subjects will be assessed for presence of disease after completion of treatment and up to three years |
| Safety and toxicity | 11 months to three years | Safety and toxicity will be assessed by CTCAE for overall toxicity and safety and Clavien-Dindo for toxicity related to surgery. |
| Patient-reported quality of life and functional outcomes (score 0-100 with 100 being best possible score) | post treatment at 7, 11 weeks and at 3 and 12 months | The University of Washington-Quality of Life (UW-QOL) to assess standard penetration-aspiration score (PAS) will be used to assess patient and observer-reported quality of life and functional outcomes. |
| clinical response | week 7 | clinical response will be determined by clinical and radiographic criteria by comparison of pretreatment and post-treatment assessment prior to surgery |
| Observer-reported quality of life and functional outcomes | post treatment at 7, 11 weeks and at 3 and 12 months | Video Fluoroscopic Swallow Study (VFSS) to assess standard penetration-aspiration score (PAS) will be used to assess patient and observer-reported quality of life and functional outcomes. |
| Immune Correlates (T-cell infiltration) | 7-11 weeks | Patients will undergo assessment of T-cell infiltration into primary tumors expressed as % staining in primary tumor sections on immunohistochemical staining. |
| Immune Correlates (shared tumor and sentinel node T-cell clones) | 7-11 weeks | Patients will undergo assessment of frequency of shared tumor and sentinel node T-cell clones as defined by absolute number of shared clones, |
| Immune Correlates (B-cell germinal centers) | 7-11 weeks | Patients will undergo assessment of number of B-cell germinal centers in draining sentinel lymph nodes compared to non-sentinel nodes as defined by average number of B-cell germinal centers per high powered field with random sampling of at least 10 high powered fields on microscopy. |
| Patient-reported quality of life and functional outcomes (score 20-100 with 100 being best possible score) | post treatment at 7, 11 weeks and at 3 and 12 months | MD Anderson Dysphagia Inventory (MDADI) to assess standard penetration-aspiration score (PAS) will be used to assess patient and observer-reported quality of life and functional outcomes. |
| clinical to pathologic down-staging | week 7-10 | clinical to pathologic down-staging will be assessed by comparing pretreatment AJCC (American Joint Committee on Cancer) VIII stage to pathologic stage determined by surgical pathology results. And decrease in overall Stage or decrease in T or N category will be defined as down staging. |
Countries
United States
Contacts
Primary ContactJoseph A Califano, MD
Outcome results
None listed