Ignite Creation Date:
2025-12-24 @ 9:59 PM
Ignite Modification Date:
2025-12-25 @ 7:37 PM
Study NCT ID:
NCT03452332
Status:
COMPLETED
Last Update Posted:
2023-09-13
First Post:
2018-02-26
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Stereotactic Body Radiation Therapy, Tremelimumab and Durvalumab in Treating Participants With Recurrent or Metastatic Cervical, Vaginal, or Vulvar Cancers
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Phase I Multi-Center Study of Hypofractionated Radiotherapy in Combination With Durvalumab and Tremelimumab in Patients With Recurrent/Metastatic Advanced Cervical, Vaginal, or Vulvar Cancer
Status:
COMPLETED
Status Verified Date:
2023-09
Last Known Status:
None
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:
This phase I trial studies how well stereotactic body radiation therapy works in combination with tremelimumab and durvalumab in treating participants with cervical, vaginal, or vulvar cancers that have come back (recurrent) or spread to other areas of the body (metastatic). 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. Immunotherapy with monoclonal antibodies, such as tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy, tremelimumab, and durvalumab may work better in treating participants with cervical, vaginal, or vulvar cancers.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine the safety, and tolerability of combined immune checkpoint blockade with 3 fractions of stereotactic body radiation therapy (stereotactic ablative radiotherapy \[SABR\]) of up to two metastatic lesions in patients with recurrent and or metastatic cervical, vaginal, or vulvar cancer.
SECONDARY OBJECTIVES:
I. To evaluate clinical response rates and assess toxicities of treatment to durvalumab combined with tremelimumab with 3 fractions of SABR of at least one and up to two metastatic lesions in patients with recurrent/metastatic cervical, vaginal, or vulvar cancer.
II. To estimate progression-free survival, overall survival, and time to next treatment.
EXPLORATORY OBJECTIVES:
I. To evaluate potential biomarkers of immune response to combined immune-checkpoint inhibition with SABR and correlate this with clinical response to treatment.
II. To evaluate potential biomarkers of immune response including cervical and rectal microbial diversity, cervical immune cell infiltration and peripheral immune cell activation as correlates of clinical response to treatment.
OUTLINE:
Participants receive tremelimumab intravenously (IV) over 1 hour followed by durvalumab IV over 1 hour on day 1 of each cycle. Participants also undergo SABR over 30-45 minutes on days 8, 10, and 12 of cycle 1. Treatment with tremelimumab repeats every 4 weeks for up to 4 cycles, and treatment with durvalumab repeats every 4 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 days, at 2, 3, 4, 6, 8, 10, and 12 months, and then every 6 months thereafter.
I. To determine the safety, and tolerability of combined immune checkpoint blockade with 3 fractions of stereotactic body radiation therapy (stereotactic ablative radiotherapy \[SABR\]) of up to two metastatic lesions in patients with recurrent and or metastatic cervical, vaginal, or vulvar cancer.
SECONDARY OBJECTIVES:
I. To evaluate clinical response rates and assess toxicities of treatment to durvalumab combined with tremelimumab with 3 fractions of SABR of at least one and up to two metastatic lesions in patients with recurrent/metastatic cervical, vaginal, or vulvar cancer.
II. To estimate progression-free survival, overall survival, and time to next treatment.
EXPLORATORY OBJECTIVES:
I. To evaluate potential biomarkers of immune response to combined immune-checkpoint inhibition with SABR and correlate this with clinical response to treatment.
II. To evaluate potential biomarkers of immune response including cervical and rectal microbial diversity, cervical immune cell infiltration and peripheral immune cell activation as correlates of clinical response to treatment.
OUTLINE:
Participants receive tremelimumab intravenously (IV) over 1 hour followed by durvalumab IV over 1 hour on day 1 of each cycle. Participants also undergo SABR over 30-45 minutes on days 8, 10, and 12 of cycle 1. Treatment with tremelimumab repeats every 4 weeks for up to 4 cycles, and treatment with durvalumab repeats every 4 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 days, at 2, 3, 4, 6, 8, 10, and 12 months, and then every 6 months thereafter.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
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?: