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

Phase 2

Completed

Conditions: primaire buikvlieskanker
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer
10038588
10033283

Registration Number: NL-OMON46453

Lead Sponsor: Astra Zeneca

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

1. Has read and understands the informed consent form (ICF) and has given written consent.;2. Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer.;3. 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.;4. No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy.;5. 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). Subjects without any prior anthracycline exposure can also be included (applies to Arm D only).;6. At least 1 measurable lesion according to RECIST v1.1.;7. Any prior palliative 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. ;8. ECOG Performance Status (PS) score of 0 - 1.;9. Baseline Laboratory Values within 7 days of starting study drugs:
a) ANC *1500/*L
b) HgB * 9 g/dL with no blood transfusions in the past 28 days
c) Platelets * 100,000/*L
d) ALT & AST * 3 x ULN or * 5 x ULN if known hepatic metastases
e) Serum bilirubin within normal limits (WNL) or *1.5 x 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.
f) Serum creatinine *1.5 x ULN OR measured creatinine clearance (CrCl) * 45 mL/min by the Cockcroft-Gault method.;10. Left ventricular ejection fraction (LVEF) WNL of the institution, as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only).;11. Female patients who are not of childbearing potential and fertile female patients of
childbearing potential who agree to use adequate contraceptive measures from 2
weeks prior to the study and until 1 month after study treatment discontinuation,
who are not breastfeeding, and who have a negative serum or urine pregnancy test
within 3 days prior to start of study treatment;12. Predicted life expectancy * 12 weeks;13. Must be *18 years of age.;14. Willingness and ability to comply with study and follow-up procedures.

Exclusion Criteria

1. Participation in another clinical investigational study within the previous 28 days. ;2. Use of a study drug (approved or investigational drug therapy) * 21 days or 5 half-lives
(whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is * 21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required.;3. Major surgical procedures * 28 days of beginning study treatment, or minor surgical
procedures * 7 days. No waiting required following port-a-cath placement, or any other central venous access placement.;4. No other chemotherapy, immunotherapy, hormonal anti-cancer therapy, radiotherapy (except for palliative local radiotherapy), biological therapy or other novel agent is permitted while the patient is receiving study medication. ;5. Grade >1 toxicity from prior therapy (except alopecia or anorexia).;6. Known malignant CNS disease other than neurologically stable, treated brain metastases * defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment.;7. Any prescription or non-prescription 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 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug.

8. Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) * Class 2:
a) Unstable angina
b) Congestive heart failure
c) Acute myocardial infarction
d) Conduction abnormality not controlled with pacemaker or medication
e) Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).;9. AZD1775 should not be given to patients with a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. AZD1775 has not ben studied in patients with ventricular arrhythmias or recent myocardial infarction.;10. Corrected QT interval (QTc) >470 msec at study entry or congenital long QT syndrome. QTc interval will be calculated using Fridericia's formula (per institutional standards) obtained from 3 ECGs performed 2-5 minutes apart at study entry.

11.Pregnant or lactating.;12. Serious active infection upon enrolment, or other serious underlying medical condition that would impair the patient's ability to receive study treatment. ;13. Presence of other active cancers, or history of treatment for invasive cancer within the last 3 years. 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.;14. Psychological, familial, sociological, or geographic conditions that do not permit compliance with the protocol.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of this study is ORR for the arms included in the efficacy<br /><br>assessment, defined as the proportion of patients achieving a complete or<br /><br>partial tumour response according to Response Evaluation Criteria in Solid<br /><br>Tumours (RECIST) v1.1 (Eisenhauer et al 2009).</p><br>

Secondary Outcome Measures