Study Stopped
slow accrual
Stereotactic Body Radiation Therapy and Durvalumab With or Without Tremelimumab Before Surgery in Treating Participants With Human Papillomavirus Positive Oropharyngeal Squamous Cell Caner
Phase Ib/II Trial of Stereotactic Body Radiotherapy (SBRT) in Cominbation With Immunotherapy Prior to Transoral Robotic Surgery (TORS) for Human Papillomavirus Positive (HPV+) Squamous Cell Carcinoma of the Head and Neck (SCCHN)
2 other identifiers
interventional
19
1 country
1
Brief Summary
This phase Ib/II trial studies the side effects and how well stereotactic body radiation therapy and durvalumab with or without tremelimumab before surgery work in treating participants with human papillomavirus positive oropharyngeal squamous cell cancer. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy and durvalumab with or without tremelimumab before surgery may work better in treating participants with oropharyngeal squamous cell cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 12, 2018
CompletedFirst Posted
Study publicly available on registry
August 7, 2018
CompletedStudy Start
First participant enrolled
October 4, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2023
CompletedNovember 18, 2023
November 1, 2023
4.7 years
July 12, 2018
November 15, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events (Phase I safety lead-in) assessed Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.03 criteria
Data from all cycles of treatment will be combined in the presentation of safety data. AEs will be listed individually by patient.
Up to 90 days after last dose
Progression-free survival (PFS) (Phase II)
The Kaplan-Meier product-limit estimate of the PFS function will be estimated and displayed. The median PFS time will be given with 95% confidence interval. Summaries of the number and percentage of patients experiencing a PFS event, and the type of event (RECIST v 1.1 or death) will be provided.
From time of enrollment to the first occurrence of disease progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 or death from any cause, assessed up to 2 years
Incidence of grade >= adverse events (Phase II)
Up to 2 years
Secondary Outcomes (10)
Overall survival (OS)
From the time of enrollment to date of death due to any cause, assessed up to 2 years
Primary tumor control determined by RECIST v. 1.1
Up to 2 years
Distant recurrence rate
Up to 2 years
Locoregional control rate
Up to 2 years
Rate of contralateral neck failure
Up to 2 years
- +5 more secondary outcomes
Study Arms (2)
Cohort I (SBRT, durvalumab, TORS, neck dissection)
EXPERIMENTALBeginning day 0 of course 1, participants undergo stereotactic body radiation therapy 5 days a week for 1 week and receive durvalumab IV over 1 hour on days 0 and 27 in the absence of disease progression or unacceptable toxicity. Participants then undergo transoral robotic surgery and modified radical neck dissection between weeks 6-8. Beginning week 12, participants then receive durvalumab IV over 1 hour every 4 weeks. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Cohort II (SBRT, durvalumab,tremelimumab,TORS,neck dissection)
EXPERIMENTALBeginning day 0 of course 1, participants undergo stereotactic body radiation therapy 5 days a week for 1 week and receive tremelimumab IV and durvalumab IV over 1 hour on days 0 and 27 in the absence of disease progression or unacceptable toxicity. Participants then undergo transoral robotic surgery and modified radical neck dissection between weeks 6-8. Beginning week 12, participants then receive durvalumab IV over 1 hour every 4 weeks. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Undergo modified radical neck dissection
Ancillary studies
Ancillary studies
Undergo SBRT
Undergo TORS
Given IV
Eligibility Criteria
You may qualify if:
- Written informed consent from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluation.
- Pathologically proven diagnosis of HPV-positive squamous cell carcinoma of the oropharynx. HPV-positivity will be defined as tumors that are p16-positive by immunohistochemistry.
- Patients must have T0-3 disease with all gross disease amenable to R0 resection (reviewed by multidisciplinary study team) and is eligible for TORS in the opinion of the treating physician.
- N0-N2b with all cervical disease confined to 2 cervical lymph node levels if the involved nodal levels are adjacent.
- Karnofsky performance status \>= 70.
- Body weight \>= 50 kg.
- Patients who are medically operable, without pre-existing medical conditions that could inhibit surgery following neoadjuvant therapy, and do not refuse surgery.
- Patients with smoking history (\< 20 pack year history) is allowed.
- Patients must have MRI neck with and without contrast and a diagnostic positron emission tomography (PET), computed tomography (CT) or PET/CT skull base to mid-thigh with contrast within 30 days prior to SBRT.
- Hemoglobin \>= 9.0 g/dL.
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (\>= 1500 per mm\^3).
- Platelet count \>= 100 (or 75) x 10\^9/L (\>= 75,000 per mm\^3).
- Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert?s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal.
- Serum creatinine \> 40 mL/min.
- +5 more criteria
You may not qualify if:
- Karnofsky performance status (KPS) \< 70.
- Body weight \< 50 kg.
- Histology other than squamous cell carcinoma.
- Primary site other than oropharynx (i.e. oral cavity, salivary glands, nasal cavity, paranasal sinuses, larynx, or nasopharynx) or of unknown primary.
- Patients with synchronous or bilateral disease.
- Patient with N3 nodal disease, N2c nodal disease, and N2b disease with gross disease in more than 2 neck levels (levels not adjacent to each others are also not allowed).
- Patients with recurrent head and neck cancer.
- Patients with metastatic disease on initial staging study.
- Patients who underwent attempted resection rather than the diagnostic biopsy of the primary site or nodal sampling of the neck disease.
- Prior systemic therapy (chemotherapy, biologic, or immunotherapy) for the same OPSCC.
- Previous treatment with Anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) including tremelimumab or PD1/PD-L1 inhibitor (programmed cell death) , including durvalumab.
- Concurrent enrollment in another clinical trial.
- Patients that received prior radiotherapy that would result in overlap of radiation therapy fields.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no evidence of active disease \>= 5 years before the first dose of study drug and of low potential risk for recurrence
- +24 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jonsson Comprehensive Cancer Centerlead
- AstraZenecacollaborator
Study Sites (1)
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Robert Chin
UCLA / Jonsson Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 12, 2018
First Posted
August 7, 2018
Study Start
October 4, 2018
Primary Completion
June 30, 2023
Study Completion
June 30, 2023
Last Updated
November 18, 2023
Record last verified: 2023-11