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
2 other identifiers
interventional
20
1 country
2
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.
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 Jul 2018
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 26, 2018
CompletedFirst Posted
Study publicly available on registry
March 2, 2018
CompletedStudy Start
First participant enrolled
July 18, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 11, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 11, 2023
CompletedSeptember 13, 2023
September 1, 2023
5.1 years
February 26, 2018
September 11, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03
Will be assessed based on dose limiting toxicities (DLTs) and based on adverse events (AEs) throughout the entire treatment period. In the overall assessment of adverse events, AEs will be tabulated by body system, type and grade, overall and by disease cohort. The number and percentage of patients experiencing at least one grade 3 or higher AE will also be reported.
Up to 3 months after last dose of durvalumab
Secondary Outcomes (4)
Response to treatment by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune-related response criteria
Up to 1 year
Progression-Free Survival
From the start of therapy up to first documented disease progression or death from any cause, assessed up to 1 year
Overall Survival
From start of therapy to death from any cause, assessed up to 1 year
Time to next treatment (TTNT)
From the end of immune-checkpoint inhibition treatment to institution of next therapy, assessed up to 1 year
Study Arms (1)
Treatment (tremelimumab, durvalumab, SABR)
EXPERIMENTALParticipants receive tremelimumab 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.
Interventions
Given IV
Undergo SABR
Given IV
Eligibility Criteria
You may qualify if:
- Written informed consent obtained from subject prior to any protocol related procedures
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.
- Body weight \> 30 kg
- Must have an average life expectancy of 6 months
- Patient is able and willing to comply with protocol and study procedures for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up visits
- Histological diagnosis of recurrent or metastatic cervical, vaginal, or vulvar cancer or an unknown pelvic malignancy most likely to have arisen from these sites as determined clinically by the treating physicians (i.e. squamous cell carcinoma or adenocarcinoma that is high risk \[HR\] human papillomavirus positive \[HPV\]+, but not limited to this example)
- Metastatic disease in at least two distinct lesions (including the index lesion to be treated) with at least one site outside of the radiation field and evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria for evaluation of response
- At least one index lesion to be treated measuring 1 cm amenable to hypofractionated radiation therapy
- Staging computed tomography (CT) scans done prior to enrollment
- Have had at least one line of prior platinum-based systemic chemotherapy once diagnosed with recurrence or metastatic disease if primary cervical cancer. If a patient has primary vulvar or vaginal cancer, there is not a requirement.
- May have received 1 prior biologic regimen (i.e. avastin) but not within 4 weeks of enrollment
- Full recovery from the acute effects of prior treatments, defined as effects having resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03 grade 0 or 1 with the exception of alopecia and certain laboratory values as outlined below; subjects with irreversible toxicity that is not reasonably expected to be exacerbated by durvalumab and tremelimumab may be included (e.g., hearing loss, neuropathy) upon approval of the principal investigator (PI)
- In patients with central nervous system (CNS) metastases, metastases must be asymptomatic at the time of day 1 of the study and meet the following criteria:
- Brain metastases should have been treated with either whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS)/gamma-knife, or surgical resection;
- At least 28 days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or CT from last day of treatment with radiation to the CNS metastases;
- +16 more criteria
You may not qualify if:
- Involvement in the planning and/or conduct of the study
- Previous enrollment in the present study
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy
- Prior treatment with an anti-CTLA-4, including tremelimumab PD-1 or PD-L1 inhibitor, including durvalumab
- Prior oncology vaccine therapy
- Prior radiation treatment to the index lesion to be treated
- Prior radiation which overlaps and precludes hypofractionated treatment to the index lesion
- Treatment with other investigational agent within 4 weeks to the first dose of tremelimumab or durvalumab
- Concomitant therapy with any of the following: interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; all such therapies must have been discontinued \> 4 weeks
- Any unresolved toxicity (CTCAE grade \< 2) from previous anti-cancer therapy; (subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)
- Any prior grade \>= 3 immune-related adverse event (imAE) while receiving any previous immunotherapy agent, or any unresolved imAE \> grade 1
- Treatment with a vascular endothelial growth factor (VEGF) inhibitor within the last 6 weeks
- Major surgical procedure (as defined by the treating physician) within 28 days prior to the first dose of durvalumab and tremelimumab or still recovering from prior surgery
- Active cardiac disease defined as unstable angina, uncontrolled hypertension, myocardial infarction in the last six months (unless successfully treated with coronary artery bypass grafting \[CABG\] or percutaneous transluminal coronary angioplasty \[PTCA\]), uncontrolled arrhythmia, or symptomatic congestive heart failure; \> 3 heart-related hospitalizations in the past year
- Mean QT interval corrected for heart rate (QTc) \>= 470 ms calculated from 3 electrocardiogram (ECGs) using Fridericia's correction from triplicate ECGs in those patients who have an initial abnormal EKG on screening
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lilie L Lin
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 26, 2018
First Posted
March 2, 2018
Study Start
July 18, 2018
Primary Completion
August 11, 2023
Study Completion
August 11, 2023
Last Updated
September 13, 2023
Record last verified: 2023-09