Ignite Creation Date:
2025-12-25 @ 12:31 AM
Ignite Modification Date:
2026-01-06 @ 2:46 AM
Study NCT ID:
NCT03450967
Status:
UNKNOWN
Last Update Posted:
2021-08-10
First Post:
2018-02-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Durvalumab Plus Tremelimumab Combined With Proton Therapy for HNSCC
Sponsor:
Samsung Medical Center
Organization:
Study Overview
Official Title:
A Phase II Study of Durvalumab (MEDI4736) Plus Tremelimumab Combined With Proton Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Status:
UNKNOWN
Status Verified Date:
2021-08
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
* Clinical Phase: phase II single arm study
* Primary Objectives: Response rate
* Number of Subjects: 27 patients
* Study Population: recurrent or metastatic head and neck squamous cell carcinoma
* Investigational Product(s), Dose, and Mode of Administration:
Durvalumab 1500mg plus tremelimumab 75mg via IV infusion Q4W, starting on Week 0, for up to a maximum of 4 doses/cycles followed by durvalumab monotherapy 1500mg via IV infusion Q4W, starting 4 weeks after the last infusion of the combination until progression.).
Proton therapy 5 GyE x 5 fractions
\- Study Assessments and Criteria for Evaluation: Safety Assessments: according to NCI CTCAE version 4.0 Efficacy Assessments: according to RECIST version 1.1
\- Statistical Methods and Data Analysis: PFS: from the date of treatment to the date of progression or death or last follow-up OS: from the date of treatment to the date of death or last follow-up
\- Sample Size Determination: Patients must have a histologically confirmed diagnosis of HNSCC. In this phase II study, up to approximately 27 eligible patients will be enrolled. It is anticipated that full accrual to this study will take approximately 24 months.
H0: Objective response rate ≤10% H1: Objective response rate ≥35% According to Simon's two-stage optimal design (power of 90% and one-sided alpha of 0.05), this study needs total 27 evaluable patients. At the first stage, 11 patients would be enrolled. If two or more among them achieve objective response, the study will go forward the second stage. At the second stage, 16 additional patients (total 27 patients) would be enrolled. Among the total 27 evaluable patients, six or more objective responses are necessary for this drug to be evaluated further in the group of R/M HNSCC
* Primary Objectives: Response rate
* Number of Subjects: 27 patients
* Study Population: recurrent or metastatic head and neck squamous cell carcinoma
* Investigational Product(s), Dose, and Mode of Administration:
Durvalumab 1500mg plus tremelimumab 75mg via IV infusion Q4W, starting on Week 0, for up to a maximum of 4 doses/cycles followed by durvalumab monotherapy 1500mg via IV infusion Q4W, starting 4 weeks after the last infusion of the combination until progression.).
Proton therapy 5 GyE x 5 fractions
\- Study Assessments and Criteria for Evaluation: Safety Assessments: according to NCI CTCAE version 4.0 Efficacy Assessments: according to RECIST version 1.1
\- Statistical Methods and Data Analysis: PFS: from the date of treatment to the date of progression or death or last follow-up OS: from the date of treatment to the date of death or last follow-up
\- Sample Size Determination: Patients must have a histologically confirmed diagnosis of HNSCC. In this phase II study, up to approximately 27 eligible patients will be enrolled. It is anticipated that full accrual to this study will take approximately 24 months.
H0: Objective response rate ≤10% H1: Objective response rate ≥35% According to Simon's two-stage optimal design (power of 90% and one-sided alpha of 0.05), this study needs total 27 evaluable patients. At the first stage, 11 patients would be enrolled. If two or more among them achieve objective response, the study will go forward the second stage. At the second stage, 16 additional patients (total 27 patients) would be enrolled. Among the total 27 evaluable patients, six or more objective responses are necessary for this drug to be evaluated further in the group of R/M HNSCC
Detailed Description:
The incidence of Head and neck cancer (HNC) is approximately 6% of all cases with a world annual incidence and nearly 90 to 95% of HNC is squamous cell carcinoma (HNSCC). \[1\] For patients with recurrent or metastatic HNSCC (R/M HNSCC), cytotoxic-based chemotherapy remains the standard therapeutic option. The median survival of these patients treated with cytotoxic-based chemotherapy, however, is only 6 to 10 months. For those who are not candidates for chemotherapy, the prognosis is even worse with median survival of 3 to 6 months. \[2-4\] Thus, new therapeutic options for these patients are needed to improve the treatment outcomes.
We hypothesize that durvalumab plus tremelimumab combined with proton therapy would be effective in R/M HNSCC.
The combination of immunotherapy and RT can be effective regimen because immunologic response might be enhanced by RT through the alteration of microenvironment within the irradiated field, tumor antigen release and "abscopal effect" at distant metastatic sites. In addition, the benefit of proton therapy is to deliver RT dose just to target lesion. The irradiated volume can be significantly reduced with proton therapy compared to X-ray treatment, thus proton therapy will provide better quality of life compared to X-ray during palliative RT.
Patients in the durvalumab (MEDI4736) + tremelimumab combination therapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 4 doses/cycles each, followed by durvalumab (MEDI4736) 1500mg Q4W until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be 4 weeks after the final dose of durvalumab (MEDI4736) in combination with tremelimumab.
Tremelimumab will be administered first; the durvalumab (MEDI4736) infusion will start approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion. If there are no clinically significant concerns after the first cycle, then, at the discretion of the Investigator, all other cycles of durvalumab (MEDI4736) can be given immediately after the tremelimumab infusion has finished.
We hypothesize that durvalumab plus tremelimumab combined with proton therapy would be effective in R/M HNSCC.
The combination of immunotherapy and RT can be effective regimen because immunologic response might be enhanced by RT through the alteration of microenvironment within the irradiated field, tumor antigen release and "abscopal effect" at distant metastatic sites. In addition, the benefit of proton therapy is to deliver RT dose just to target lesion. The irradiated volume can be significantly reduced with proton therapy compared to X-ray treatment, thus proton therapy will provide better quality of life compared to X-ray during palliative RT.
Patients in the durvalumab (MEDI4736) + tremelimumab combination therapy treatment group will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 4 doses/cycles each, followed by durvalumab (MEDI4736) 1500mg Q4W until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. The first durvalumab (MEDI4736) monotherapy dose at 1500mg Q4W will be 4 weeks after the final dose of durvalumab (MEDI4736) in combination with tremelimumab.
Tremelimumab will be administered first; the durvalumab (MEDI4736) infusion will start approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion. If there are no clinically significant concerns after the first cycle, then, at the discretion of the Investigator, all other cycles of durvalumab (MEDI4736) can be given immediately after the tremelimumab infusion has finished.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: