Trials / Completed
CompletedNCT03452332
Stereotactic Body Radiation Therapy, Tremelimumab and Durvalumab in Treating Participants With Recurrent or Metastatic Cervical, Vaginal, or Vulvar Cancers
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
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 20 (actual)
- Sponsor
- M.D. Anderson Cancer Center · Academic / Other
- Sex
- Female
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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.
Conditions
- Advanced Cervical Adenocarcinoma
- Advanced Vaginal Carcinoma
- Advanced Vulvar Carcinoma
- Human Papillomavirus-Related Cervical Squamous Cell Carcinoma
- Human Papillomavirus-Related Vulvar Squamous Cell Carcinoma
- Metastatic Cervical Adenocarcinoma
- Metastatic Cervical Carcinoma
- Metastatic Cervical Squamous Cell Carcinoma, Not Otherwise Specified
- Metastatic Vaginal Adenocarcinoma
- Metastatic Vaginal Carcinoma
- Metastatic Vulvar Carcinoma
- Recurrent Cervical Adenocarcinoma
- Recurrent Cervical Carcinoma
- Recurrent Cervical Squamous Cell Carcinoma, Not Otherwise Specified
- Recurrent Vaginal Carcinoma
- Recurrent Vulvar Carcinoma
- Stage III Cervical Cancer AJCC v8
- Stage III Vaginal Cancer AJCC v8
- Stage III Vulvar Cancer AJCC v8
- Stage IIIA Cervical Cancer AJCC v8
- Stage IIIA Vulvar Cancer AJCC v8
- Stage IIIB Cervical Cancer AJCC v8
- Stage IIIB Vulvar Cancer AJCC v8
- Stage IIIC Vulvar Cancer AJCC v8
- Stage IV Cervical Cancer AJCC v8
- Stage IV Vaginal Cancer AJCC v8
- Stage IV Vulvar Cancer AJCC v8
- Stage IVA Cervical Cancer AJCC v8
- Stage IVA Vaginal Cancer AJCC v8
- Stage IVA Vulvar Cancer AJCC v8
- Stage IVB Cervical Cancer AJCC v8
- Stage IVB Vaginal Cancer AJCC v8
- Stage IVB Vulvar Cancer AJCC v8
- Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
- Vulvar Adenocarcinoma
- Vulvar Squamous Cell Carcinoma
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | Durvalumab | Given IV |
| OTHER | Laboratory Biomarker Analysis | Correlative studies |
| RADIATION | Stereotactic Radiosurgery | Undergo SABR |
| BIOLOGICAL | Tremelimumab | Given IV |
Timeline
- Start date
- 2018-07-18
- Primary completion
- 2023-08-11
- Completion
- 2023-08-11
- First posted
- 2018-03-02
- Last updated
- 2023-09-13
Locations
2 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT03452332. Inclusion in this directory is not an endorsement.