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Summary

for females ages 18–130 (full criteria)
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

A Phase II Study of AZD1775 plus Chemotherapy in Patients with Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Patients will receive AZD1775 plus carboplatin or AZD1775 plus weekly paclitaxel. The primary study objective is to evaluate the objective response rate (ORR).

Official Title

A Multicentre Phase II Study of AZD1775 Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Details

This is a phase II study of AZD1775 plus chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients will receive AZD1775 plus carboplatin or AZD1775 plus weekly paclitaxel.

The primary endpoint for the study is overall response rate (ORR) defined as the proportion of patients achieving a complete or partial tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Secondary endpoints include assessment of the duration of response (DoR), overall survival (OS), progression-free survival (PFS), disease control rate (DCR), Gynecologic Cancer Intergroup (GCIG) cancer antigen-125 response, safety and tolerability, clinically significant changes in safety-related laboratory parameters, pharmacokinetics (PK) and drug-drug interactions.

A Safety Review Team (SRT) will assess the safety and tolerability of the first 6 patients in each arm by incidence and severity of adverse events (AEs) after a minimum of 1 treatment cycle as determined by NCI CTCAE v4.03 and the occurrence of pre-defined dose-limiting toxicities (DLTs). Patients must complete Cycle 1 safety evaluations, and return to the study centre for Cycle 2 Day 1 evaluations to be considered evaluable for the safety lead-in.

Arm B: Arm B (AZD1775 + paclitaxel) will enroll approximately 30 additional patients at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.

Arm C2: Initially, 6 patients will be enrolled to receive 5 doses of AZD1775 in approx. 12 hour intervals over the first 2.5 days of Weeks 1, 2, and 3 (i.e., Days 1-3, 8-10, and 15-17) of each 28 day cycle. If 1 patient or less experiences a DLT during Cycle 1, then 6 more patients will be enrolled for a total of 12. However, if 2 or more of the first 6 patients experience a DLT then the AZD1775 dosing may be modified to 2 weeks on followed by 1 week off. All patients will receive carboplatin on Day 1 of each 28 day cycle. AZD1775 should be taken approximately 2 hours before or 2 hours after food. Patients may continue on study as long as they are benefitting, have no evidence of disease progression, and do not meet any criteria for discontinuation or withdrawal.

Enrollment in Arms A and C is complete. Enrollment will not continue in Arm D.

Keywords

Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Paclitaxel Albumin-Bound Paclitaxel Carboplatin

Eligibility

For females ages 18–130

Inclusion

  1. Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.
  2. Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease(progression during platinum-containing therapy) are ineligible.
  3. No more than 2 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.
  4. Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m2 or cumulative epirubicin dose of ≤ 720 mg/m2 (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin).
  5. At least 1 measurable lesion according to RECIST v1.1.
  6. Radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment.
  7. ECOG Performance Status (PS) score of 0 - 1.
  8. Baseline Laboratory Values:
  9. ANC ≥1500/μL
  10. HgB ≥ 9 g/dL
  11. Platelets> 100,000/μL
  12. ALT & AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases
  13. Serum bilirubin within normal limits (WNL) or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
  14. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method.
  15. Left ventricular ejection fraction (LVEF) WNL as determined by multiple gated acquisition (MUGA) or echocardiography (ECHO).
  16. Female patients, ≥18, (not of childbearing potential and fertile female patients of childbearing potential) who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start.
  17. Predicted life expectancy ≥ 12 weeks

    Exclusion

  18. Any study drug ≤ 21 days or 5 half-lives (whichever is shorter) prior to the first dose.
  19. Major surgical procedures ≤ 28 days of beginning study, or minor surgical procedures ≤7 days.
  20. Grade>1 toxicity from prior therapy (except alopecia or anorexia).
  21. Known CNS disease other than neurologically stable, treated brain metastases (e.g.,metastasis having no evidence of progression or haemorrhage after treatment for ≥2 weeks)
  22. Any Rx or non Rx drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 and withheld throughout the study until 2 weeks after last dose.Co-administration of aprepitant during this study is prohibited.
  23. Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2:
  24. Unstable angina
  25. Congestive heart failure
  26. Acute myocardial infarction
  27. Conduction abnormality not controlled with pacemaker or medication
  28. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
  29. Corrected QT interval (QTc)>470 msec at study entry or congenital long QT syndrome.
  30. Pregnant or lactating.
  31. Serious active infection upon enrolment, or other serious underlying medical condition that would impair the patient's ability to receive study treatment.
  32. Presence of other active cancers, or history of treatment for invasive cancer within 3 years. Patients with Stage I cancer who have received definitive local treatment within 3 years, and whom are considered unlikely to recur, are eligible. Patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.

Locations

  • Research Site accepting new patients
    San Francisco, California, United States
  • Research Site accepting new patients
    Los Angeles, California, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
AstraZeneca
ID
NCT02272790
Phase
Phase 2
Lead Scientist
Lee-May Chen
Study Type
Interventional
Last Updated
May 1, 2017
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