An experimental medicine, External Beam Radiation Therapy, and Cisplatin

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"Experimental combination treatment for Cervical, Upper Vaginal, and Uterine Cancers"
Age: 18 and older
Gender:
Female
Healthy Volunteers: No
Keywords: uterine, ovarian, cervical, kinase, cancer, radiotherapy, phase 1, phase I, phase one
Type: Drug study, Phase 1
Target:
33 Participants
Investigator:
Description
This study examines the side effects and best dose of an experimental medicine called AZD1775. It will be studied when given together with external beam radiation therapy and cisplatin. The experimental drug is being developed to treat patients with cervical, vaginal or uterine cancer.

The experimental medicine AZD1775 inhibits an important protein. It 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.

Chemotherapy drugs work in different ways to stop the growth of tumor cells. They either kill the cells by stopping them from dividing, or by stopping them from spreading. Giving all three treatments may work better in treating patients with cervical, vaginal, or uterine cancer.
This study requires

All study participants will receive the study drug AZD1775 given with standard radiotherapy and cisplatin. AZD1775 is a capsule that you will take by mouth once a day. Some days you will take the capsules in the hospital, but other days you will take AZD1775 at home. The dose of the AZD1775 you receive will depend on when you enroll in the study. The study doctor will tell you to which of the following groups you have been assigned:

Group 1: dose escalation

Different doses of the study drug AZD1775 will be given to several study participants. The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until side effects occur that require the dose to be lowered.

Group 2: verifying the dose (expansion group)

The dose of AZD1775 identified in group 1 will be tested further in the next 15 participants. The dose of the study drug might be decreased or kept the same depending on the side effects.

Study schedules for groups 1 and 2:

The AZD1775 capsules will be taken on days 1, 3, 5 of each week, or on days 1-5 of each week. The study doctor will tell you which schedule you are on.

All participants will receive regular radiotherapy on days 1-5 for each week for 5 weeks, and regular Cisplatin chemotherapy on day 1 or day 3 of each week for 5 weeks

The Patient Study Drug Diary will explain how to take and record taking the study drug capsules and will also describe your schedule. The dose of the AZD1775 you receive can be lowered or delayed if there are excessive side effects.

Who can participate

Inclusion criteria:

  • 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
  • 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
  • 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
  • Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR) =< 1.5 upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x institutional upper limits of normal; unless due to Gilbert's syndrome
  • Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal level
  • Patients must be able to swallow whole capsules
  • 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 or her partner is participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria:

  • Patients who have received any radiotherapy or chemotherapy for their current gynecological cancer
  • Patients who received prior pelvic radiotherapy for any indication
  • Patients requiring para-aortic radiotherapy
  • Patients who are receiving any other investigational agents or anticancer therapy concurrently or within 4 weeks (ie 28 days)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD1775 or cisplatin
  • Patients taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice) are ineligible: sensitive CYP3A4 substrates, CYP3A4 substrates with a narrow therapeutic index, moderate to potent inhibitors / inducers of CYP3A4; patients would be eligible if the medications can be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication
  • Uncontrolled intercurrent illness including, but not limited to, myocardial infarction within 6 months, congestive heart failure, symptomatic congestive heart failure, unstable angina pectoris, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, active liver disease or cerebrovascular disease with previous stroke, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with AZD1775 and cisplatin; these potential risks may also apply to other agents used in this study
  • Patients with another uncontrolled malignancy; patients with a previous malignancy, treated curatively and without evidence of disease relapse are eligible
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • History of active clinically significant bleeding
  • History of bowel obstruction or malabsorption syndromes (within the last 3 months) which might limit the absorption of the study drug
Benefits and risks of participating
BENEFITS:

We cannot promise any benefit to you as a result of taking part in this research study.

RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid for taking part in this study.
Resources
Schedule
Study duration and period
You will take the study drug for 5 weeks. After you finish the treatment, the study doctor will ask you to visit the office for follow-up exams for up to two years.
Recruitment period
From Dec. 15, 2017
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Contact
Frances Lara
Research Topic
Conditions:
  • Endometrioid Adenocarcinoma
  • Recurrent Cervical Carcinoma
  • Stage I Uterine Corpus Cancer AJCC v7
  • Stage I Vaginal Cancer AJCC v6 and v7
  • Stage IA Uterine Corpus Cancer AJCC v7
  • Stage IB Cervical Cancer AJCC v6 and v7
  • Stage IB Uterine Corpus Cancer AJCC v7
  • Stage II Cervical Cancer AJCC v7
  • Stage II Uterine Corpus Cancer AJCC v7
  • Stage II Vaginal Cancer AJCC v6 and v7
  • Stage IIA Cervical Cancer AJCC v7
  • Stage IIB Cervical Cancer AJCC v6 and v7
  • Stage III Cervical Cancer AJCC v6 and v7
  • Stage III Uterine Corpus Cancer AJCC v7
  • Stage III Vaginal Cancer AJCC v6 and v7
  • Stage IIIA Cervical Cancer AJCC v6 and v7
  • Stage IIIA Uterine Corpus Cancer AJCC v7
  • Stage IIIB Cervical Cancer AJCC v6 and v7
  • Stage IIIB Uterine Corpus Cancer AJCC v7
  • Stage IIIC Uterine Corpus Cancer AJCC v7

Have any questions or want to learn more? Leave your contact details below and the research team will reach out to you.


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