Durvalumab, Tremelimumab + Radiotherapy in Gynecologic Cancer

NCT03277482 | Terminated Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 17-382
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is evaluating the safety and effectiveness of 2 immunotherapy drugs in combination with radiation therapy as a possible treatment for recurrent or metastatic gynecologic cancer. The names of the immunotherapy drugs involved in this study are:

• Durvalumab
• Tremelimumab

Conditions

Recurrent Gynecological Cancer; Metastatic Cervical Cancer; Metastatic Ovarian Cancer; Metastatic Vaginal Cancer; Metastatic Vulvar Cancer; Metastatic Endometrial Cancer; Recurrent Cervical Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Recurrent Endometrial Cancer

Keywords

Recurrent gynecological cancer; Metastatic Cervical Cancer; Metastatic Ovarian Cancer; Metastatic Vaginal Cancer; Metastatic Vulvar Cancer; Metastatic Endometrial Cancer; Recurrent Cervical Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer; Recurrent Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Radiotherapy with durvalumab and tremelimumab

  Incidence of dose-limiting toxicities for each dose level or regimen

  8 Weeks

Secondary Outcomes (7)

• Overall Response Rate

  One Year

• Local Response Rate

  One Year

• Local Control Rate

  Baseline to 6 months, 12 Months

• Abscopal Response Rate

  One Year

• Response Duration

  One Year

Study Arms (2)

Phase I Safety Lead-In

EXPERIMENTAL

A modified 3+3 design will be used in this trial Lead-in phase with Durvalumab\* and radiation therapy \*q4 weeks durvalumab for 13 cycles or until progression

Drug: Durvalumab; Radiation: Radiation Therapy

Phase I Radiation Dose Evaluation

EXPERIMENTAL

* Durvalumab * Tremelimumab\* -- Start radiation dose from safety lead-in (level 0 or level -1) \*q4 weeks durvalumab / tremelimumab for 4 cycles and continue durvalumab for 13 cycles or until disease progression

Drug: Durvalumab; Drug: Tremelimumab; Radiation: Radiation Therapy

Interventions

Durvalumab DRUG

Durvalumab is given by intravenous infusion every 4 weeks for a maximum of 13 doses over 52 weeks. One cycle is defined as every 4 weeks. Each infusion will take approximately 1 hour.

Also known as: Imfinizi, MEDI4736

Phase I Radiation Dose Evaluation; Phase I Safety Lead-In

Tremelimumab DRUG

Tremelimumab is given by intravenous infusion every 4 weeks for a maximum of 4 doses over 16 weeks. One cycle is defined as every 4 weeks. If receiving both durvalumab and tremelimumab for the first 4 cycles, they will be given on the same day. Each infusion will take approximately 1 hour

Also known as: CP-675,206, CP-675

Phase I Radiation Dose Evaluation

Radiation Therapy RADIATION

Radiation treatment will begin on the same day as the first immunotherapy infusion or on the following day. The radiation treatment course is either 1 day or 5 days.

Phase I Radiation Dose Evaluation; Phase I Safety Lead-In

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Participants must have histologically or cytologically confirmed endometrial, ovarian (including ovarian epithelial, fallopian tube, primary peritoneal), cervical, vaginal, or vulvar cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Participants must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥20 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. See also 3.1.10 as all measurable/target lesions must not be located within the planned radiation field for the expansion cohort.
• Patients must have progressive disease following prior therapy. Specifically, patients must have progressed on platinum-based chemotherapy.
• At least 21 days must have elapsed from prior therapy (chemotherapy or radiation).
• Age of 18 years or older. Because no dosing or adverse event data are currently available on the use of durvalumab in combination with tremelimumab and radiation in patients \<18 years of age, children are excluded from this study.
• ECOG performance status ≤1 (Karnofsky ≥60%, see Appendix A).
• Body weight of greater than 30 kg.
• Participants must have normal organ and marrow function as defined below:
• Hgb \>=9g/dl
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin \<=1.5 x normal institutional limits.
• \--- This last criterion will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia \[predominantly unconjugated bilirubin\] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician.
• AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal

You may not qualify if:

• Prior exposure to immune-mediated therapy, including anti-PD-1, anti-PD-L1 (including durvalumab) or anti-CTLA-4 directed therapy (including tremelimumab). Therapeutic anticancer vaccines are not included in this category. Exposure to other investigational agents may be permitted after discussion with the Study PI.
• Chemotherapy, targeted therapy, biologic or hormonal agents within 3 weeks prior to entering the study.
• Radiation therapy within 3 weeks prior to entering the study.
• Current receipt of any other investigational agents.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients 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.
• Patients with untreated brain metastases, spinal cord compression, or leptomeningeal carcinomatosis are excluded from this clinical trial because of their poor prognosis, because of symptoms that may arise from inflammatory reactions, and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with brain metastases or spinal cord compression previously treated with radiation and/or surgery are allowed if local treatment was \>30 days ago, most recent MRI demonstrates stability or decrease in size of all lesions, and the patient has no current neurologic symptoms related to the metastases and treatment and no requirement for corticosteroids related to the prior treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tremelimumab and durvalumab or previous toxicity attributed to durvalumab or other PD-1 or PD-L1 directed therapy that led to drug discontinuation.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, interstitial lung disease, pneumonitis, active peptic ulcer disease or gastritis, active bleeding diatheses, or serious chronic gastrointestinal conditions associated with diarrhea.
• Pregnant women are excluded from this study because durvalumab and tremelimumab are immune checkpoint inhibitors with the potential for teratogenic or abortifacient effects, as is radiation therapy.
• A nursing mother unwilling to discontinue breastfeeding. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with durvalumab, tremelimumab and radiation, breastfeeding should be discontinued if the mother is treated with durvalumab, tremelimumab and radiation.
• Female patients who are pregnant or breastfeeding or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period
• HIV-positive patients are ineligible due to the risks associated with immune checkpoint blockade.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab and tremelimumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AstraZeneca: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Fitzgerald KJ, Konstantinopoulos P, Matulonis U, Liu J, Horowitz N, Lee E, Kolin DL, Lee L, King M. A phase I clinical trial of radiation therapy, durvalumab and tremelimumab in recurrent gynecologic cancer. Gynecol Oncol. 2025 Jun;197:51-56. doi: 10.1016/j.ygyno.2025.04.006. Epub 2025 Apr 23.

  PMID: 40273550 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Ovarian Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms; Endometrial Neoplasms

Interventions

durvalumab; tremelimumab; Radiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Vaginal Diseases; Vulvar Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Martin King, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 11, 2017
• Study Start: June 1, 2018
• Primary Completion: July 15, 2022
• Study Completion: July 15, 2022
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)