Clinical Trials /

Adavosertib Before Surgery in Treating Patients With Advanced High Grade Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT02659241

Description:

This pilot early phase I trial studies how adavosertib affects the tumor deoxyribonucleic acid (DNA) of patients undergoing surgery for high grade (fast growing or aggressive) ovarian, fallopian tube, or primary peritoneal cancer that has spread to other places in the body. Certain characteristics in the DNA of these patients may affect how well they respond to treatment. Learning how adavosertib affects DNA in tumor cells may help doctors plan effective treatment.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Adavosertib Before Surgery in Treating Patients With Advanced High Grade Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
  • Official Title: A Pilot Study of Wee1 Inhibition Induction Prior to Tumor Reductive Surgery in Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2015-0519
  • SECONDARY ID: NCI-2016-00118
  • SECONDARY ID: 2015-0519
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02659241

Conditions

  • Carcinomatosis
  • Elevated Serum CA-125 Tumor Antigen
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal High Grade Serous Adenocarcinoma
  • Stage III Fallopian Tube Cancer AJCC v7
  • Stage III Ovarian Cancer AJCC v6 and v7
  • Stage III Primary Peritoneal Cancer AJCC v7
  • Stage IIIA Fallopian Tube Cancer AJCC v7
  • Stage IIIA Ovarian Cancer AJCC v6 and v7
  • Stage IIIA Primary Peritoneal Cancer AJCC v7
  • Stage IIIB Fallopian Tube Cancer AJCC v7
  • Stage IIIB Ovarian Cancer AJCC v6 and v7
  • Stage IIIB Primary Peritoneal Cancer AJCC v7
  • Stage IIIC Fallopian Tube Cancer AJCC v7
  • Stage IIIC Ovarian Cancer AJCC v6 and v7
  • Stage IIIC Primary Peritoneal Cancer AJCC v7
  • Stage IV Fallopian Tube Cancer AJCC v6 and v7
  • Stage IV Ovarian Cancer AJCC v6 and v7
  • Stage IV Primary Peritoneal Cancer AJCC v7

Interventions

DrugSynonymsArms
AdavosertibAZD-1775, AZD1775, MK-1775, MK1775Basic Science (adavosertib)

Purpose

This pilot early phase I trial studies how adavosertib affects the tumor deoxyribonucleic acid (DNA) of patients undergoing surgery for high grade (fast growing or aggressive) ovarian, fallopian tube, or primary peritoneal cancer that has spread to other places in the body. Certain characteristics in the DNA of these patients may affect how well they respond to treatment. Learning how adavosertib affects DNA in tumor cells may help doctors plan effective treatment.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To explore baseline levels and effects of adavosertib (AZD1775) on DNA copy number,
      mutation, and level of ribonucleic acid (RNA) and protein expression (together described as
      "molecular results") in tumor protein p53 (p53)-related pathways before and after treatment
      in women with primary advanced high grade serous ovarian, fallopian tube, or primary
      peritoneal cancer.

      SECONDARY OBJECTIVES:

      I. To correlate molecular results to clinical endpoints including response and survival.

      II. To correlate molecular results to pathologic endpoints including tumor volume and
      apoptosis.

      III. To compare DNA copy number and level of RNA and protein expression in p53-related
      pathways in tissue from patients treated with AZD1775 to those untreated with AZD1775 in the
      preoperative period.

      IV. To determine the toxicity of AZD1775 given preoperatively, with a focus on postoperative
      wound healing.

      V. To determine the feasibility of treating preoperatively with AZD1775.

      OUTLINE:

      Patients receive adavosertib orally (PO) once daily (QD) on days 1-5. Patients then undergo
      standard of care laparoscopy. Patients may also receive adavosertib PO QD on days 8-12,
      15-19, and 22-26 for up to 28 days based on surgery schedule.

      After completion of study treatment, patients are followed up at 30 days and then every 3
      months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Basic Science (adavosertib)ExperimentalPatients receive adavosertib PO QD on days 1-5. Patients then undergo standard of care laparoscopy. Patients may also receive adavosertib PO QD on days 8-12, 15-19, and 22-26 for up to 28 days based on surgery schedule.
  • Adavosertib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with presumed advanced-stage high grade serous ovarian, fallopian tube, or
             primary peritoneal carcinoma, based on the presence of carcinomatosis, and/or elevated
             cancer antigen (CA)125, and/or ovarian mass(es), or at the discretion of the treating
             physician

          -  Medically able to undergo primary cytoreductive surgery, at least 13 days and up to 28
             days after starting study drug, as determined by treating physician

          -  No prior therapy for high-grade serous ovarian, fallopian tube, or primary peritoneal
             carcinoma

          -  Patients must be able to swallow and tolerate oral medications and not have
             gastrointestinal illnesses that would preclude absorption of AZD1775 (e.g.
             uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome; ulcerative
             disease); Note: patient may not have a percutaneous endoscopic gastrostomy (PEG) tube
             or be receiving total parenteral nutrition (TPN)

          -  Absolute neutrophil count >= 1,500/mcL (within 7 days prior to initiation of therapy)

          -  Hemoglobin >= 9 gm/dL (within 7 days prior to initiation of therapy)

          -  Platelets >= 100,000/mcL (within 7 days prior to initiation of therapy)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 7 days prior to
             initiation of therapy)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
             limit of normal unless the liver is involved with tumor, in that case, AST and ALT
             must be =< 5 x upper limit of normal (within 7 days prior to initiation of therapy)

          -  Creatinine clearance > 50 mL/min (assessed by Cockcroft Gault estimation) and
             creatinine < 1.5 x ULN (within 7 days prior to initiation of therapy)

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 or 1

          -  Women of childbearing potential (WoCBP) may be included only if acceptable
             contraception is in place for two weeks before study entry, for the duration of the
             study and for 90 days after the last dose of AZD1775; WoCBP are defined as those who
             are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or
             complete hysterectomy) or postmenopausal (defined as 12 months with no menses without
             an alternative medical cause); acceptable methods of contraception include true
             abstinence in line with the preferred and usual lifestyle choice of the patient, tubal
             ligation, vasectomized partner, barrier methods (eg, cap plus spermicide, sponge plus
             spermicide, diaphragm plus spermicide, or male condom plus a spermicide), intrauterine
             device methods (eg, Copper T or Levonorgestrel-releasing intrauterine system), or
             hormonal methods (eg, any registered and marketed contraceptive agent that contains an
             oestrogen and/or a progestational agent and that is administered via the oral,
             subcutaneous, transdermal, intrauterine, or intramuscular route as an implant, hormone
             shot or injection, combined pill, minipill or patch); all methods of contraception
             (with the exception of total abstinence) should be used in combination with the use of
             a condom by their male sexual partner for intercourse; periodic abstinence, the rhythm
             method, and the withdrawal method are not acceptable methods of birth control; all
             WoCBP must have a negative pregnancy test within 3 days prior to study the initiation
             of therapy; should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately

          -  Women must not breast-feed while taking the study medications

          -  Patients must be able to understand and willing to sign an informed consent

        Exclusion Criteria:

          -  Prior treatment for ovarian, fallopian tube, or primary peritoneal cancer

          -  Current receipt of any other investigational agents or any additional anti-cancer
             agents for this or any other disease

          -  Known central nervous system (CNS) disease other than neurologically stable, treated
             brain metastases -- defined as metastasis having no evidence of progression or
             hemorrhage after treatment for at least 2 weeks

          -  Presence of other active cancers; patients with stage I cancer who have received
             definitive local treatment within the last 3 years, and whom are considered unlikely
             to recur, are eligible; all patients with previously treated in-situ carcinoma (i.e.,
             non-invasive) are eligible, as are patients with prior non-melanoma skin cancers

          -  Major surgical procedures =< 28 days of beginning study treatment, or minor surgical
             procedures =< 7 days (minor procedures done at time of laparoscopy are allowed); no
             waiting required following port-a-cath placement

          -  Significant symptom burden from presumed diagnosis including large volume ascites,
             pain requiring narcotic medication, or shortness of breath on exertion

          -  Myocardial infarction within 6 months before starting therapy, symptomatic congestive
             heart failure (New York Heart Association > class II), unstable angina, or unstable
             cardiac arrhythmia requiring medication

          -  Corrected QT interval (QTc) > 470 msec (as calculated by Fridericia correction
             formula) at study entry or congenital long QT syndrome

          -  Caution should be exercised when inhibitors or substrates of P-glycoprotein (P-gP),
             substrates of cytochrome P450 family 1 subfamily A member 2 (CYP1A2) with a narrow
             therapeutic range, sensitive substrates of cytochrome P450 family 2 subfamily C member
             19 (CYP2C19) or CYP2C19 substrates with a narrow therapeutic range are administered
             with AZD1775

          -  Herbal preparations are not allowed throughout the study; these herbal medications
             include, but are not limited to: St. John's wort, kava, ephedra (ma huang), gingko
             biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng; not willing
             to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos,
             and exotic citrus fruits from 14 days prior to the dose of study medication and during
             the entire study due to potential CYP3A4 interaction with the study medication; orange
             juice is allowed

          -  Any known hypersensitivity or contraindication to the components of study treatment

          -  Pregnant or breast-feeding

          -  As judged by the investigator, any evidence of severe or uncontrolled systemic
             diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral,
             diffuse, parenchymal lung disease], uncontrolled chronic renal diseases
             [glomerulonephritis, nephritic syndrome, Fanconi syndrome or renal tubular acidosis]),
             serious active infection or current unstable or uncompensated respiratory or cardiac
             conditions, or uncontrolled hypertension (blood pressure >= 140/90), active bleeding
             diatheses or active infection including hepatitis B, hepatitis C, and human
             immunodeficiency virus; screening for chronic conditions and infectious diseases is
             not required

          -  As judged by the investigator, the patient is unsuitable to participate in the study
             and the patient is unlikely to comply with study procedures, restrictions, and
             requirements

          -  Subject has had prescription or non-prescription drugs or other products known to be
             sensitive cytochrome P450 family 3 subfamily A member 4 (CYP3A4) substrates or CYP3A4
             substrates with a narrow therapeutic index, or to be moderate to strong inhibitors /
             inducers of CYP3A4 which cannot be discontinued two weeks prior to day 1 of dosing and
             withheld throughout the study until 2 weeks after the last dose of study drug;
             co-administration of aprepitant or fosaprepitant during this study is prohibited

          -  The use of statins including atorvastatin are prohibited and patients should be moved
             on to non-breast cancer resistance protein (BCRP) alternatives
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in level of deoxyribonucleic acid (DNA) copy number in p53-related pathways
Time Frame:Baseline up to 28 days
Safety Issue:
Description:Descriptive statistics and graphical methods will be used to summarize the change in DNA copy number from pre-treatment to post-treatment with adavosertib. These changes for untreated patients will also be summarized. A paired t-test will be used to test that mean changes from pre-treatment to post-treatment are different from 0 if the changes are found to be normally distributed. Otherwise, median changes from pre-treatment to post-treatment will be tested with a Wilcoxon signed-rank test. A 2-sample t-test will be used to compare mean changes between treated and untreated patients if the changes are normally distributed. Otherwise, median changes will be compared between treated and untreated patients with a Wilcoxon rank sum test.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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