Clinical Trials /

AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma

NCT03668340

Description:

This research study is studying an investigational drug as a possible treatment for uterine cancer. The drug involved in this study is: -AZD1775

Related Conditions:
  • Endometrial Serous Adenocarcinoma
  • Uterine Carcinosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma
  • Official Title: A Phase 2 Study of the Wee1 Inhibitor AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma

Clinical Trial IDs

  • ORG STUDY ID: 18-316
  • NCT ID: NCT03668340

Conditions

  • Uterine Cancer

Interventions

DrugSynonymsArms
AZD1775Part A: AZD1775

Purpose

This research study is studying an investigational drug as a possible treatment for uterine cancer. The drug involved in this study is: -AZD1775

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved AZD1775 as a treatment for
      any disease.

      The "investigational drug" AZD1775 is being given alone to patients with this type of cancer.
      AZD1775 is also being studied in lung cancer, ovarian cancer, and other solid tumors
      throughout the world. AZD1775 blocks the activity of Wee1, a protein that helps to regulate
      how cells divide and grow. Certain cancer cells may be more vulnerable to having this process
      blocked. This study is being done to assess the safety and effectiveness of AZD1775 to learn
      if AZD1775 works in treating this type of cancer.
    

Trial Arms

NameTypeDescriptionInterventions
Part A: AZD1775Experimental-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle
  • AZD1775
Part B: AZD1775 in CarcinosarcomaExperimental-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle
  • AZD1775
Part C: AZD1775 in Uterine Serous with biopsiable diseaseExperimental-AZD1775 will be taken by mouth daily on days 1 through 5 and days 8 through 12 of each 21-day cycle
  • AZD1775

Eligibility Criteria

        Inclusion Criteria:

          -  Participants in Parts A and C must have histologically or cytologically confirmed
             recurrent or persistent uterine serous carcinoma. For the purposes of this study,
             uterine carcinomas (with the exception of carcinosarcomas) that have any component
             that is considered serous will be considered a uterine serous carcinoma.

          -  Participants in Part B must have histologically or cytologically confirmed recurrent
             uterine carcinosarcoma. Additionally, the following features must also be present:

               -  Presence of a p53 alteration (by either IHC or next generation sequencing)

               -  Metastatic or extra-uterine component must be confirmed on pathology to be from
                  the carcinoma component of the disease

               -  Patients without confirmation that the metastatic or extrauterine component of
                  disease is of carcinoma histology may be considered after discussion with the PI

          -  Participants must have measurable disease, defined as at least one lesion that can be
             accurately measured per RECIST 1.1 criteria. See Section 11 for the evaluation of
             measurable disease.

          -  Participants must have had one prior platinum-based chemotherapy regimen for
             management of advanced or metastatic uterine serous carcinoma or uterine
             carcinosarcoma. Chemotherapy administered only in conjunction with primary RT as a
             radiosensitizer should not count as a systemic regimen. There is no restriction on the
             number of prior lines of therapy a participant may have previously received.

          -  Age 18 years or older.

          -  ECOG performance status 0 or 1 (see Appendix A)

          -  Participants must have normal organ and marrow function as defined below:

               -  absolute neutrophil count ≥1,500/mcL

               -  hemoglobin ≥9 g/dL

               -  platelets ≥100,000/mcL

               -  total bilirubin ≤ upper limit of normal (ULN) or ≤1.5x ULN in patients with liver
                  metastases or well-documented Gilbert's Syndrome.

               -  AST(SGOT)/ALT(SGPT) ≤3 × ULN or ≤5 × ULN in patients with liver metastases

               -  creatinine ≤1.5 × ULN OR

               -  creatinine clearance ≥45 mL/min/1.73 m2 as calculated by the Cockroft-Gault
                  method for participants with creatinine levels above institutional normal.

          -  Willingness to release archival tissue for research purposes.

          -  Participants in Part C must have biopsiable disease (in a lesion that is not being
             utilized as the target lesion for RECIST assessment) and be willing to undergo pre-
             and on-treatment biopsies. Participants in Part B with biopsiable disease must be
             willing to undergo pre- and on-treatment biopsies.

          -  The effects of AZD1775 on the developing human fetus are unknown. For this reason,
             women of child-bearing potential must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) from 2 weeks prior to study entry and for
             1 month after study drug discontinuation. Please see Appendix C for "Definition Women
             of Childbearing Potential and Acceptable Contraceptive Methods." Patients of
             child-bearing potential should not be breastfeeding, and must have a negative serum or
             urine pregnancy test within 3 days prior to the start of study treatment. Should a
             woman become pregnant or suspect she is pregnant while she 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:

          -  Participants who have had chemotherapy, radiotherapy, or investigational therapy
             within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of
             AZD1775, or those who have not recovered to Grade 1 from adverse events (excluding
             alopecia or anorexia) due to agents administered more than 3 weeks earlier.
             Participants may not have had hormonal therapy within 2 weeks of the first dose of
             AZD1775.

          -  Participants who are receiving any other investigational agents.

          -  Participants who have MSI-high or MMR-deficient tumors will not be eligible unless
             they have already received prior therapy with pembrolizumab or another PD1/PD-L1
             immune checkpoint inhibitor or are deemed not to be a candidate for immune checkpoint
             therapy.

          -  Participants with known brain metastases or other CNS disease should be excluded from
             this clinical trial because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events. Participants with treated brain metastases that have no
             evidence of progression or hemorrhage for at least 2 weeks after treatment will be
             allowed on study.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to AZD1775.

          -  Participants may not have had prior receipt of a cell cycle checkpoint inhibitor
             (e.g., Chek1, Wee1, or ATR inhibition)

          -  Participants receiving any medications or substances that are sensitive CYP3A4
             substrates or are CYP3A4 substrates with a narrow therapeutic index, or which are
             moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued two
             weeks prior to Day 1 of dosing and withheld through the study until 2 weeks after the
             last dose of study drug. Co-administration of aprepitant or fosaprepitant during this
             study is prohibited.

          -  Transporter studies (in vitro) have shown that AZD1775 is an inhibitor of breast
             cancer resistance protein (BRCP). Please see Appendix B for additional details
             regarding prohibited drugs and drugs to be used with caution, including drugs affected
             by CYP3A4 or BRCP. Because the lists of these agents are constantly changing, it is
             important to also regularly consult a frequently-updated list such as
             http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as
             the Physicians' Desk Reference may also provide this information.

          -  Participants must not have undergone major surgical procedures within 28 days of
             beginning study treatment or minor surgical procedures within 7 days of beginning
             study treatment. Port-a-cath placement will be allowed within a 7 day window of
             starting study treatment.

          -  Participants must be able to swallow oral medication and may not have a percutaneous
             endoscopic gastrostomy (PEG) tube, be receiving total parenteral nutrition (TPN), or
             be dependent on IV fluid support.

          -  Participants with any of the following cardiac diseases currently or within the last 6
             months as defined by the New York Heart Association (NYHA) ≥ Class 2 will not be
             eligible:

               -  Unstable angina pectoris

               -  Congestive heart failure

               -  Acute myocardial infarction

               -  Conduction abnormality not controlled with pacemaker or medication

               -  Significant ventricular or supraventricular arrhythmias (patients with chronic
                  rate-controlled atrial fibrillation in the absence of other cardiac abnormalities
                  are eligible).

          -  Participants with a mean resting corrected QT interval (QTc) ≥ 480msec at study entry,
             as calculated by the Frederica formula (QTcF) by institutional standards obtained from
             an electrocardiogram (ECG) or congenital long QT syndrome. (Note: if one ECG
             demonstrates a QTcF >480 msec, then a mean QTcF of ≤ 480 msec obtained from 3 ECGs 2-5
             minutes apart is required at study entry.

          -  Participants with any concomitant or prior invasive malignancies are ineligible with
             the following exceptions:

               -  Treated limited-stage basal cell or squamous cell carcinoma of the skin

               -  Carcinoma in situ of the breast or cervix

               -  Prior cancer treated with curative intent with no evidence of recurrent disease 3
                  years following diagnosis and judged by the investigator to be at low risk of
                  recurrence

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because AZD1775 is an agent with an
             unknown potential for teratogenic or abortifacient effects. Because there is an
             unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with AZD1775, breastfeeding should be discontinued if the
             mother is treated with AZD1775.

          -  Known HIV-positive participants are ineligible because of the potential for
             pharmacokinetic interactions of antiretroviral medications with AZD1775 and the
             potential for an increased risk of lethal infections for these participants when
             treated with marrow-suppressive therapy.

          -  Because the composition, PK, and metabolism of many herbal supplements are unknown,
             the concurrent use of all herbal supplements is prohibited during the study
             (including, but not limited to, cannabis, St. John's wort, kava, ephedra [m huang],
             ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, and ginseng).
             Participants should stop herbal medications at least 7 days prior to first dose of
             AZD1775.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:2 years
Safety Issue:
Description:Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009]

Secondary Outcome Measures

Measure:Clinical benefit rate
Time Frame:2 years
Safety Issue:
Description:Clinical benefit rate is defined as response rate plus stable disease x 6 months.
Measure:Duration of Response
Time Frame:2 years
Safety Issue:
Description:The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Measure:Assess the toxicities of AZD1775 in women with recurrent or persistent uterine serous carcinoma or uterine carcinosarcoma using CTCAE v4
Time Frame:2 years
Safety Issue:
Description:Toxicities will be assessed using CTCAE v4.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Uterine Cancer

Last Updated

June 22, 2020