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History of Changes for Study: NCT03345784
WEE1 Inhibitor AZD1775, External Beam Radiation Therapy, and Cisplatin in Treating Patients With Cervical, Vaginal, or Uterine Cancer
Latest version (submitted June 28, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 16, 2017 None (earliest Version on record)
2 November 20, 2017 Conditions and Study Status
3 November 29, 2017 Contacts/Locations and Study Status
4 February 5, 2018 Contacts/Locations and Study Status
5 February 12, 2018 Arms and Interventions and Study Status
6 March 2, 2018 Study Status
7 March 19, 2018 Contacts/Locations and Study Status
8 April 26, 2018 Outcome Measures, Arms and Interventions, Study Description, Study Identification, Eligibility, Study Design, Conditions and Study Status
9 May 3, 2018 Contacts/Locations and Study Status
10 May 4, 2018 Study Status
11 June 6, 2018 Contacts/Locations and Study Status
12 June 12, 2018 Contacts/Locations and Study Status
13 June 13, 2018 Contacts/Locations and Study Status
14 June 18, 2018 Contacts/Locations and Study Status
15 July 26, 2018 Outcome Measures and Study Status
16 July 30, 2018 Contacts/Locations and Study Status
17 August 1, 2018 Contacts/Locations and Study Status
18 August 3, 2018 Study Status
19 September 10, 2018 Study Status
20 October 4, 2018 Contacts/Locations and Study Status
21 March 8, 2019 Contacts/Locations, Study Status, Eligibility and Study Identification
22 March 28, 2019 Contacts/Locations and Study Status
23 April 15, 2019 Contacts/Locations and Study Status
24 April 19, 2019 Contacts/Locations and Study Status
25 May 27, 2019 Contacts/Locations and Study Status
26 June 3, 2019 Arms and Interventions and Study Status
27 July 9, 2019 Contacts/Locations and Study Status
28 August 12, 2019 Arms and Interventions, Study Description, Oversight and Study Status
29 August 19, 2019 Study Status
30 October 1, 2019 Arms and Interventions and Study Status
31 October 7, 2019 Arms and Interventions and Study Status
32 November 11, 2019 Contacts/Locations and Study Status
33 November 13, 2019 Contacts/Locations and Study Status
34 November 18, 2019 Arms and Interventions and Study Status
35 December 9, 2019 Study Status
36 January 20, 2020 Study Status
37 February 3, 2020 Study Status
38 February 19, 2020 Study Status
39 March 2, 2020 Study Status
40 March 3, 2020 Contacts/Locations and Study Status
41 March 9, 2020 Contacts/Locations and Study Status
42 March 12, 2020 Contacts/Locations, Conditions and Study Status
43 March 13, 2020 Contacts/Locations and Study Status
44 March 18, 2020 Contacts/Locations and Study Status
45 April 14, 2020 Study Status
46 May 12, 2020 Contacts/Locations and Study Status
47 June 13, 2020 Study Status
48 June 17, 2020 Contacts/Locations and Study Status
49 July 8, 2020 Outcome Measures, Conditions, Study Status and Study Identification
50 July 16, 2020 Study Status
51 July 21, 2020 Recruitment Status, Study Status and Contacts/Locations
52 July 22, 2020 Study Status
53 October 16, 2020 Study Status
54 October 17, 2020 Study Status
55 April 20, 2021 Study Status
56 September 7, 2021 Arms and Interventions and Study Status
57 October 28, 2021 Study Status
58 November 9, 2021 Arms and Interventions and Study Status
59 April 22, 2022 Study Status
60 June 7, 2022 Arms and Interventions and Study Status
61 June 28, 2022 Arms and Interventions and Study Status
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Study NCT03345784
Submitted Date:  November 16, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: NCI-2017-00038
Brief Title: WEE1 Inhibitor AZD1775, 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 Radiotherapy and Cisplatin in Cervical, Upper Vaginal and, Uterine Cancers (10041848, 10008224, 10008238, 10046888, 10014735)
Secondary IDs: NCI-2017-00038 [Registry Identifier: CTRP (Clinical Trial Reporting Program)]
2013-01765
PHL-087
10132 [University Health Network Princess Margaret Cancer Center LAO]
10132 [CTEP]
UM1CA186644 [U.S. NIH Grant/Contract]
Open or close this module Study Status
Record Verification: November 2017
Overall Status: Recruiting
Study Start: October 23, 2017
Primary Completion: October 18, 2020 [Anticipated]
Study Completion: October 18, 2020 [Anticipated]
First Submitted: November 16, 2017
First Submitted that
Met QC Criteria:
November 16, 2017
First Posted: November 17, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
November 16, 2017
Last Update Posted: November 17, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: National Cancer Institute (NCI)
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: This phase I trial studies the side effects and best dose of WEE1 inhibitor AZD1775 when given together with external beam radiation therapy and cisplatin in treating patients with cervical, vaginal, or uterine cancer. WEE1 inhibitor AZD1775 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 WEE1 inhibitor AZD1775, external beam radiation therapy, and cisplatin may work better in treating patients with cervical, vaginal, or uterine cancer.
Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose (RP2D) and safety profile of WEE1 inhibitor AZD1775 (AZD1775) in combination with radiotherapy 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 radiotherapy and concurrent cisplatin.

II. To evaluate the pharmacodynamic effects of AZD1775 when administered in combination with radiotherapy 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 of AZD1775 in combination with standard radiotherapy and concurrent cisplatin in women with gynecological cancer.

OUTLINE: This is a dose-escalation study of WEE1 inhibitor AZD1775.

Patients undergo external beam radiation therapy on days 1-5 and receive WEE1 inhibitor AZD1775 orally (PO) on days 1, 3, and 5 or 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.

Open or close this module Conditions
Conditions: Endometrioid Adenocarcinoma
Recurrent Cervical Carcinoma
Stage I Uterine Corpus Cancer
Stage I Vaginal Cancer
Stage IA Uterine Corpus Cancer
Stage IB Cervical Cancer
Stage IB Uterine Corpus Cancer
Stage II Cervical Cancer
Stage II Uterine Corpus Cancer
Stage II Vaginal Cancer
Stage IIA Cervical Cancer
Stage IIB Cervical Cancer
Stage III Cervical Cancer
Stage III Uterine Corpus Cancer
Stage III Vaginal Cancer
Stage IIIA Cervical Cancer
Stage IIIA Uterine Corpus Cancer
Stage IIIB Cervical Cancer
Stage IIIB Uterine Corpus Cancer
Stage IIIC Uterine Corpus Cancer
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 24 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Treatment (radiation therapy, cisplatin, AZD1775)
Patients undergo external beam radiation therapy on days 1-5 and receive WEE1 inhibitor AZD1775 PO on days 1, 3, and 5 or days 1-5 and cisplatin 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.
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: External Beam Radiation Therapy
Undergo external beam radiation therapy
Other Names:
  • Definitive Radiation Therapy
  • EBRT
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Drug: WEE1 Inhibitor AZD1775
Given PO
Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775
Open or close this module Outcome Measures
Primary Outcome Measures:
1. RP2D defined as the dose level with < 1/6 patients with dose limiting toxicities
[ Time Frame: Up to week 5 ]

Secondary Outcome Measures:
1. Incidence of acute adverse events assessed by National Cancer Institute (NCI) Clinical Trials Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
[ Time Frame: Up to 2 years ]

Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a subanalysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.
2. Incidence of late adverse events assessed by NCI CTCAE version 4.0
[ Time Frame: Up to 2 years ]

Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a subanalysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.
3. Objective response assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria
[ Time Frame: Up to 2 years ]

4. Pharmacodynamic effects of WEE1 inhibitor AZD1775 when given in combination with radiation therapy and cisplatin
[ Time Frame: Up to 2 years ]

Pharmacodynamic biomarkers will include: pCDC2, Ki67, γH2AX, pH3, and CC3. Associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics; however, logistic regression may be used if warranted.
5. Progression-free survival
[ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Female
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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
Open or close this module Contacts/Locations
Study Officials: Stephanie Lheureux
Principal Investigator
University Health Network Princess Margaret Cancer Center LAO
Locations: United States, North Carolina
Duke University Medical Center
[Suspended]
Durham, North Carolina, United States, 27710
Canada, Ontario
University Health Network Princess Margaret Cancer Center LAO
[Recruiting]
Toronto, Ontario, Canada, M5G 2M9
Contact:Contact: Stephanie Lheureux 416-946-2415 stephanie.lheureux@uhn.ca
Contact:Principal Investigator: Stephanie Lheureux
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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