A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination with Durvalumab, Followed by Maintenance Durvalumab with or without Olaparib in Patients with Newly Diagnosed Advanced

This study is being done to learn more about how durvalumab and olaparib, when combined with standard of care chemotherapy, could improve outcomes for women with endometrial cancer. This study will also serve to better understand endometrial cancer and associated health problems.

Durvalumab is a type of anti-cancer drug called immunotherapy that targets cancer cells by blocking the signal that prevents the immune system from seeing the cancer cell. Your immune system can then attack and kill the cancer cells.

Olaparib is a type of drug called a PARP (poly [adenosine diphosphate-ribose] polymerase) inhibitor. PARP inhibitors can destroy cancer cells that are not good at repairing DNA damage. Olaparib is taken orally in tablet form. Olaparib is approved by the FDA and in other countries for maintenance treatment for recurrent, epithelial ovarian, fallopian tube or primary peritoneal adult cancer, regardless of BRCA status.

Durvalumab and Olaparib are still in the development stage for the treatment of endometrial cancer, and they are not approved by the Food and Drug Administration (FDA) for treatment of endometrial cancer. Therefore, both these medicines are considered as experimental treatments for patients with endometrial cancer.

The untested parts of the study are the addition of durvalumab to chemotherapy and the addition of durvalumab with or without olaparib following chemotherapy.

Participants will be given one of three different treatments:

• Standard of care chemotherapy
• Durvalumab with chemotherapy followed by Durvalumab
• Durvalumab with chemotherapy followed by Durvalumab and Olaparib

Inova Schar Cancer Institute
8081 Innovation Park Drive
Fairfax, VA 22031
A department of Inova Fairfax Hospital

• Females ages 18 and above
• Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies, including carcinosarcomas, will be allowed. Sarcomas will not be allowed
• Additional eligibility in protocol

• Pregnancy/breastfeeding
• Any unresolved toxicity National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE version 5.0) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Note:
  • Patients with Grade ≥2 neuropathy may be included only after consultation with the study physician
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or olaparib may be included only after consultation with the study physician
• Major surgical procedure (as defined by the investigator) within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable or diagnostic staging
• History of allogenic organ transplantation
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, 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:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients with coeliac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic
• Additional ineligibility in protocol

Additional information can be found at: https://clinicaltrials.gov/ct2/show/NCT04269200