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

Who is this study for? Adult female patients with cancers of reproductive system including cervical cancer
What treatments are being studied? Adavosertib+Cisplatin+External Beam Radiation Therapy
Status: Terminated
Location: See all (8) locations...
Intervention Type: Drug, Radiation
Study Type: Interventional
Study Phase: Phase 1
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 tumor cells by blocking some of the enzymes needed for cell growth. External beam radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. 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. Giving adavosertib, external beam radiation therapy, and cisplatin may work better in treating patients with cervical, vaginal, or uterine cancer.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Healthy Volunteers: f
View:

• Patients must have one of the following biopsy proven gynecological cancer and a decision to treat with radiotherapy and concurrent cisplatin chemotherapy (RT-CT)

‣ Newly diagnosed epithelial carcinoma of the cervix, cT1B-3B, N0/1, M0/1

∙ Patient may have small volume metastatic disease in para-aortic or supraclavicular lymph nodes or at other metastatic sites as long as, in the best judgment of the treatment team, a radical course of pelvic radiotherapy is warranted to assure local disease control

⁃ Newly diagnosed epithelial carcinoma of the upper 1/3 vagina, T1-3, N0/1, M0/1

∙ Patient may have small volume metastatic disease in para-aortic or supraclavicular lymph nodes or at other metastatic sites as long as, in the best judgment of the treatment team, a radical course of pelvic radiotherapy is warranted to assure local disease control

⁃ Newly diagnosed endometrioid adenocarcinoma of the uterus, cT1-3, N0/1, M0 unsuitable for primary surgery because of the extent of local disease; these patients are eligible if a prior decision has been made to treat radically with neoadjuvant chemoradiation followed by surgery or further radiotherapy (including brachytherapy) depending on response

⁃ Central pelvis or sidewall recurrence of epithelial carcinoma of the cervix of endometrioid adenocarcinoma of the uterus after previous surgery without previous pelvic radiotherapy

• Patients must be planned to receive whole pelvic radiotherapy to a total dose of 45 Gy or greater

• Patients must be able to receive weekly cisplatin

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky \>= 60%)

• Life expectancy of greater than 3 months

• Leukocytes \>= 3,000/mcL

• Absolute neutrophil count \>= 1,500/mcL

• Platelets \>= 100,000/mcL

• Hemoglobin \>= 9 g/dL

‣ Blood transfusions are allowed at any time during the screening, treatment or follow-up period, according to the center recommendations

• Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR) =\< 1.5 upper limit of normal (ULN)

• Total bilirubin: serum bilirubin within normal limits (WNL) or =\< 1.5 x ULN in patients with liver metastases; or total bilirubin =\< 3.0 x ULN with direct bilirubin WNL in patients with documented Gilbert's syndrome

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]): Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN) or =\< 5 x ULN if known hepatic metastases

• Creatinine clearance (CrCl) \>= 60 mL/min as calculated by the Cockcroft-Gault method

• Patients must be able to swallow whole capsules

• The effects of AZD1775 on the developing human fetus are unknown; the preclinical chromosomal aberrations assays have shown potential to induce chromosomal aberrations; in addition, cisplatin and radiotherapy are known to be teratogenic; for this reason, women of child-bearing potential must agree to use two birth control methods (two barrier methods or a barrier method plus a hormonal method) or abstinence prior to study entry, for the duration of study participation prior to study entry, for the duration of study participation, and for 4 months after coming off study; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately

• Females with child-bearing potential must have had a negative serum pregnancy test result =\< 28 days prior to the first dose of study treatment

• Ability to understand and the willingness to sign a written informed consent document

Locations
United States
California
University of California Davis Comprehensive Cancer Center
Sacramento
Colorado
UCHealth University of Colorado Hospital
Aurora
Kentucky
University of Kentucky/Markey Cancer Center
Lexington
North Carolina
Duke University Medical Center
Durham
New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick
Other Locations
Canada
University Health Network-Princess Margaret Hospital
Toronto
BCCA-Vancouver Cancer Centre
Vancouver
Time Frame
Start Date: 2018-05-29
Completion Date: 2022-05-10
Participants
Target number of participants: 10
Treatments
Experimental: Treatment (radiation therapy, adavosertib, cisplatin)
Patients undergo external beam radiation therapy on days 1-5 and receive adavosertib PO on days 1, 3, and 5 or QD on days 1-5 and cisplatin IV over 1 hour on day 1 or 3. Cycles repeat each week for up to 5 weeks in the absence of disease progression of unacceptable toxicity.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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