9 Participants Needed

Brachytherapy + Immunotherapy for Recurrent Gynecological Cancer

VB
Overseen ByVincent Basehart
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Jonsson Comprehensive Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any concurrent cancer treatments, and there is a required washout period (time without taking certain medications) of at least 21 days for previous anticancer therapies before starting the study drug.

What data supports the effectiveness of the drug combination of durvalumab and tremelimumab for treating recurrent gynecological cancer?

The combination of durvalumab and tremelimumab has shown effectiveness in improving survival in other cancers, such as non-small cell lung cancer and hepatocellular carcinoma, when used with chemotherapy. This suggests potential benefits for recurrent gynecological cancer, although direct evidence for this specific condition is not yet available.12345

Is the combination of durvalumab and tremelimumab generally safe for humans?

The combination of durvalumab and tremelimumab has been studied in various cancers, showing that serious side effects can occur, such as reduced appetite and diarrhea. In one study, 63.6% of patients experienced severe side effects, mostly related to chemotherapy, but the combination's safety profile was considered expected.15678

How is the treatment of brachytherapy combined with durvalumab and tremelimumab unique for recurrent gynecological cancer?

This treatment is unique because it combines brachytherapy (a type of internal radiation therapy) with two immunotherapy drugs, durvalumab and tremelimumab, which work by enhancing the body's immune response to fight cancer cells. This combination aims to improve outcomes by using both radiation and immune system activation, which is different from traditional chemotherapy or radiation alone.123910

What is the purpose of this trial?

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.

Research Team

AJ

Albert Chang, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for women with certain gynecological cancers (like ovarian, endometrial, or cervical) that haven't responded to platinum therapy and may have spread. Participants should be in good enough health to undergo internal radiation, not pregnant, able to consent, and without serious infections like TB or hepatitis. They shouldn't have used checkpoint inhibitors before or had recent major surgery.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1.5 (or 1.0) x (>= 1500 per mm^3)
Hemoglobin >= 9.0 g/dL
Subjects must consent to provide an archived tumor specimen from within 12 months prior to study entry
See 13 more

Exclusion Criteria

I have received an organ transplant from another person.
I've had radiation where the treatment area overlaps with where they plan to do brachytherapy.
I have previously used checkpoint inhibitors.
See 24 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive durvalumab or tremelimumab intravenously, followed by brachytherapy. Durvalumab is administered every 28 days for up to 13 cycles, and tremelimumab for 2-4 cycles. Brachytherapy is administered every 21 days for 3 fractions.

Up to 12 months
Multiple visits for IV administration and brachytherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks

Treatment Details

Interventions

  • Durvalumab
  • Internal Radiation Therapy
  • Tremelimumab
Trial Overview The study tests brachytherapy combined with the immune-boosting drugs Durvalumab or Tremelimumab on gynecological cancers resistant to standard treatments. It aims to see if placing radioactive material near tumors plus immunotherapy can effectively kill cancer cells and prevent growth.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm II (tremelimumab, brachytherapy)Experimental Treatment2 Interventions
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.
Group II: Arm I (durvalumab, brachytherapy)Experimental Treatment2 Interventions
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.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

🇪🇺
Approved in European Union as Imfinzi for:
  • Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸
Approved in United States as Imfinzi for:
  • Extensive-stage small cell lung cancer (ES-SCLC)
  • Limited-stage small cell lung cancer (LS-SCLC)
  • Locally advanced or metastatic urothelial carcinoma
🇯🇵
Approved in Japan as Imfinzi for:
  • Not specified in provided sources

Find a Clinic Near You

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials
373
Recruited
35,200+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

This phase II study aims to evaluate the effectiveness of combining durvalumab and tremelimumab with neoadjuvant chemotherapy in improving progression-free survival (PFS) in patients with advanced-stage ovarian cancer, specifically those with stage IIIC/IV epithelial ovarian cancer.
The study will involve 24 patients and will assess immune biomarkers and changes in the tumor microenvironment through serial biopsies, with the primary goal of achieving a 12-month PFS rate, while also monitoring safety.
A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D.Lee, JY., Kim, JW., Lim, MC., et al.[2020]
Tremelimumab shows linear pharmacokinetics with a two-compartment model, and its clearance varies depending on whether it is used as monotherapy or in combination with durvalumab, with a 16% increase in clearance for monotherapy and a 17% decrease for combination therapy over one year.
Factors like higher body weight and lower albumin levels lead to higher drug clearance, but no dosage adjustments are needed, as a flat dose of 75 mg provides similar exposure to the weight-based dosing of 1 mg/kg in adults.
Population pharmacokinetic modelling of tremelimumab in patients with advanced solid tumours and the impact of disease status on time-varying clearance.Hwang, M., Chia, YL., Zheng, Y., et al.[2023]
Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.
The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.
Durvalumab: First Global Approval.Syed, YY.[2022]

References

A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D. [2020]
Population pharmacokinetic modelling of tremelimumab in patients with advanced solid tumours and the impact of disease status on time-varying clearance. [2023]
Durvalumab: First Global Approval. [2022]
Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). [2023]
Tremelimumab: First Approval. [2023]
Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]
Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. [2022]
Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. [2022]
Tremelimumab. [2023]
10.United Statespubmed.ncbi.nlm.nih.gov
Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review. [2023]
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