AZD1775, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer

Stage IIB Cervical Cancer Clinical Trial

Official title: A Phase I Study of the Wee 1 Kinase (Wee 1) Inhibitor AZD1775 (MK-1775) in Combination With Cisplatin and Radiation in Cervical Cancer (10041848, 10008224, 10008328)

Status Suspended

Clinical Trial Summary

This phase I trial studies the side effects and best dose of WEE1 inhibitor MK-1775 (AZD1775) when given together with cisplatin and radiation therapy in treating patients with cervical cancer. WEE1 inhibitor MK-1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells. Giving WEE1 inhibitor MK-1775 together with cisplatin and radiation therapy may be a better treatment for patients with cervical cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose (RP2D) and safety profile of AZD1775 (MK-1775) in combination with cisplatin and radiation in patients with cervical cancer (phase I).

SECONDARY OBJECTIVES:

I. To evaluate the pharmacodynamic effects of AZD1775 (MK-1775) drugs when administered in combination with cisplatin and radiation (in particular, for the 15 patients treated in an expansion cohort at the RP2D). Pharmacodynamic biomarkers will include: phosphorylated cell division cycle protein 2 homolog (pCDC2), antigen Ki-67 (Ki67), gamma H2A histone family, member X (gH2AX), phosphorylated (phospho)-histone 3 (pH3), and cleaved caspase-3 (CC3).

II. To obtain preliminary information about the progression-free survival of AZD1775 (MK-1775) in combination with standard radiation and chemotherapy in women with locally advanced high-risk cervix cancer.

III. To determine the acute and late toxicity of AZD1775 (MK-1775) when administered to patients with cervix cancer in combination with standard radiation and concurrent chemotherapy.

IV. To correlate the serum pharmacokinetic parameters—maximum concentration (Cmax), time to peak concentration (Tmax), 8-hours concentration (C8), and area under the curve (AUC) (0-8)—with the drug concentration in the tumor tissue (for patients in the expansion cohort).

OUTLINE: This is a dose-escalation study of WEE1 inhibitor MK-1775. Patients are assigned to 1 of 3 treatment groups.

COHORT I: Patients receive WEE1 inhibitor MK-177 orally (PO) twice daily (BID) on days 1-2, 8-9, 15-16, 22-23, and 29-30.

COHORT II: Patients receive WEE1 inhibitor MK-177 PO BID on days 4-5, 11-12, 18-19, 25-26, and 32-33 or on days 3-5, 10-12, 17-19, 24-26, and 31-33.

COHORT III: Patients receive WEE1 inhibitor MK-177 PO BID on days 1-5, 8-12, 15-19, 22-26, and 29-33.

In all cohorts, patients also receive cisplatin intravenously (IV) over 1 hour on days 1, 8, 15, 22, and 29 and undergo of pelvic external beam radiation therapy 5 days a week for 5 weeks followed by pulsed-dose rate or high-dose rate brachytherapy 5 days a week in weeks 6-8.

After completion of study treatment, patients are followed up at 4 weeks, at 3, 6, and 12 months. ;

Related Conditions & MeSH terms

• Stage IB Cervical Cancer
• Stage IIA Cervical Cancer
• Stage IIB Cervical Cancer
• Stage IIIA Cervical Cancer
• Stage IIIB Cervical Cancer
• Uterine Cervical Neoplasms

• NCT number: NCT01958658
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Suspended
• Phase: Phase 1
• Start date: September 5, 2013