Brachytherapy With Durvalumab or Tremelimumab for the Treatment of Patients With Platinum-Resistant, Refractory, Recurrent, or Metastatic Gynecological Malignancies

NCT04395079 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19-000459NCI-2020-01095
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects and how well brachytherapy with durvalumab or tremelimumab work for the treatment of gynecological malignancies that is resistant to platinum therapy (platinum-resistant), does not respond to treatment (refractory), has come back (recurrent), or has spread to other places in body (metastatic). Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is being done to see whether brachytherapy with durvalumab or tremelimumab works better in treating patients with gynecological malignancies.

Conditions

Recurrent Malignant Female Reproductive System Neoplasm; Refractory Malignant Female Reproductive System Neoplasm; Platinum-Resistant Malignant Female Reproductive System Neoplasm; Metastatic Malignant Female Reproductive System Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (safety lead-in)

  Toxicity will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 criteria.

  Up to 90 days

• Progression free survival (PFS) (dose expansion)

  PFS will be estimated in each study arm by Kaplan-Meier estimate, where PFS is a composite endpoint based on radiologic progression, clinical deterioration or death. Furthermore, log rank test will be used to test if there is significant difference in PFS between two arms. In addition, PFS will be also estimated for localized subjects and metastatic subjects separately within each arm and stratified log rank test will be used as well.

  From the first day of the treatment to the first occurrence of disease progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 or death, assessed up to 2 years

Secondary Outcomes (6)

• Local control at the irradiated site

  Up to 2 years

• Overall response rate (ORR)

  Up to 2 years

• Response at non-irradiated lesions in subjects with multiple sites of disease

  Up to 2 years

• Duration of response (DoR)

  Up to 2 years

• Disease-specific survival

  From the first day of treatment to the date of death related to treatment and/or disease, assessed up to 2 years

Study Arms (2)

Arm I (durvalumab, brachytherapy)

EXPERIMENTAL

Patients receive durvalumab IV on day 1. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo brachytherapy on day 8. Treatment repeats every 21 days for 3 fractions in the absence of disease progression or unacceptable toxicity.

Biological: Durvalumab; Radiation: Internal Radiation Therapy

Arm II (tremelimumab, brachytherapy)

EXPERIMENTAL

Patients receive tremelimumab IV on day 1. Treatment repeats every 28 days for 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo brachytherapy on day 8. Treatment repeats every 21 days for 3 fractions in the absence of disease progression or unacceptable toxicity.

Radiation: Internal Radiation Therapy; Biological: Tremelimumab

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Arm I (durvalumab, brachytherapy)

Internal Radiation Therapy RADIATION

Undergo brachytherapy

Also known as: Brachytherapy, Brachytherapy, NOS, Internal Radiation, Internal Radiation Brachytherapy, Radiation Brachytherapy, Radiation, Internal

Arm I (durvalumab, brachytherapy); Arm II (tremelimumab, brachytherapy)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, Ticilimumab

Arm II (tremelimumab, brachytherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with platinum-resistant or refractory, recurrent or metastatic gynecological malignancies, including ovarian, endometrial, or cervical cancer are eligible for enrollment. Subjects unsuitable or refusing platinum-based chemotherapy are allowed to enrolled
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. Thus, subjects with metastatic disease must have at least 1 lesion, not previously irradiated, that can be accurately measured at baseline as \>=10 mm in the longest diameter (except lymph nodes which must have a short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate repeated measurement as per RECIST v1.1 guidelines
• Disease amenable to be treated safely with brachytherapy
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \>= 12 weeks
• Subjects must consent to provide an archived tumor specimen from within 12 months prior to study entry (ie, from subject signing consent to participate in the study). If not available, subjects should have at least 1 lesion amenable to biopsy and consent to provide a pre-treatment fresh biopsy. Additional archival tissue from beyond 12 months prior to study entry is also requested, if available, to support exploratory analyses
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \>= 1.5 (or 1.0) x (\>= 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) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =\< 5 x ULN
• Creatinine \< 3 x upper limit of normal
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply

You may not qualify if:

• Prior use of checkpoint inhibitors
• Prior radiation in which the 50% isodose line overlaps with intended site for brachytherapy
• Radiation treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Participation in another clinical study with an investigational therapeutic pharmaceutical agent i.e. chemotherapy, targeted therapy, or immunotherapy =\< 21 days or =\< 5 half-lives
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) =\< 21 days or 5 half-lives prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or pharmacokinetics (PK) properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator
• Subjects with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
• Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician
• Any concurrent chemotherapy, investigation product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
• History of allogenic organ transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Interventions

durvalumab; Immunoglobulin G; Disulfides; Brachytherapy; tremelimumab

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Radiotherapy; Therapeutics

Study Officials

• Albert J Chang

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: May 20, 2020
• Study Start: August 7, 2020
• Primary Completion: October 11, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 9, 2026

Record last verified: 2025-07

Locations

US (1)