Adavosertib, External Beam Radiation Therapy, and Cisplatin in Treating Patients With Cervical, Vaginal, or Uterine Cancer

Official Title

A Phase I Study of the Wee 1 Kinase (Wee 1) Inhibitor AZD1775 in Combination With Radiation Therapy and Cisplatin in Cervical, Upper Vaginal, and Uterine Cancers (10041848, 10008224, 10008238, 10046888, 10014735)

Summary:

This phase I trial studies the side effects and best dose of adavosertib when given together with external beam radiation therapy and cisplatin in treating patients with cervical, vaginal, or uterine cancer. Adavosertib may stop the growth of tumour cells by blocking some of the enzymes needed for cell growth. External beam radiation therapy uses high energy x-rays to kill tumour cells and shrink tumours. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumour cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving adavosertib, external beam radiation therapy, and cisplatin may work better in treating patients with cervical, vaginal, or uterine cancer.

Trial Description

Primary Outcome:

  • Recommended phase 2 dose defined as the dose level with < 1/6 patients with dose limiting toxicities
Secondary Outcome:
  • Objective response assessed according to local investigator
  • Pharmacodynamic effects of adavosertib when given in combination with radiation therapy and cisplatin
  • Progression-free survival
  • Incidence of acute adverse events assessed by National Cancer Institute (NCI) Clinical Trials Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (version 5.0 beginning April 1, 2018)
  • Incidence of late adverse events assessed by NCI CTCAE version 4.0 (version 5.0 beginning April 1, 2018)
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) and safety profile of adavosertib (AZD1775) in combination with radiation therapy and concurrent cisplatin in patients with gynecological cancers. SECONDARY OBJECTIVES:
I. To determine the acute and late toxicity of AZD1775 when administered to patients with gynecological cancer in combination with standard radiation therapy and concurrent cisplatin. II. To evaluate the pharmacodynamic effects of AZD1775 when administered in combination with radiation therapy and concurrent cisplatin (in particular, for the 15 patients treated in an expansion cohort at the RP2D). III. To obtain preliminary information about the progression-free survival, as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or clinical progression, of AZD1775 in combination with standard radiation therapy and concurrent cisplatin in women with gynecological cancer. OUTLINE:

This is a dose-escalation study of adavosertib. Patients undergo external beam radiation therapy on days 1-5 and receive adavosertib orally (PO) on days 1, 3, and 5 or once daily (QD) on days 1-5 and cisplatin intravenously (IV) over 1 hour on day 1 or 3. Courses repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity. After completion of study treatment, patients are followed up at 28 days and then every 4 months for 2 years.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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