EFFORT: Efficacy of AZD1775 in Parp Resistance; A Randomized 2-Arm, Non-Comparative Phase 2 Study of AZD1775 Alone or AZD1775 and Olaparib in Women With Ovarian Cancer Who Have Progressed During PARP Inhibition
This phase II trial studies how well adavosertib with or without olaparib work in treating
patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back
(recurrent). Adavosertib and olaparib may stop the growth of tumor cells by blocking some of
the enzymes needed for cell growth.
I. To determine the objective response rate (ORR) as determined by Response Evaluation
Criteria in Solid Tumors version 1.1 (RECIST 1.1) of adavosertib (AZD1775) alone or in
combination with olaparib in women with recurrent ovarian cancer in whom progression has been
documented following poly ADP-ribose polymerase (PARP) inhibitor therapy.
I. To evaluate the overall safety and tolerability of AZD1775 alone or in combination with
olaparib in this population.
II. To evaluate the disease control rate (DCR) = overall response rate (ORR) plus stable
disease rate for 16 weeks.
III. To evaluate the progression free survival (PFS) and overall survival (OS) of this
population following AZD1775 alone or in combination with olaparib.
IV. To evaluate the duration of response by RECIST version (v)1.1.
I. To evaluate the efficacy of each arm by BRCA-mutation status (BRCA-mt) and homologous
recombination deoxyribonucleic acid (DNA) repair deficiencies (HRD).
II. To describe endogenous and dynamic markers of DNA damage response in tumor tissue and
circulating surrogates, such as circulating tumor cells (CTC), circulating tumor DNA (ctDNA),
exosomes (cellular/nuclear), cell cycle kinetics (CDKs), and immunophenotype.
III. To examine genomic alterations associated with response and mechanisms of resistance to
olaparib and/or AZD1775.
OUTLINE: Patients are randomized to 1 of 2 arms. If enrollment pauses for 1 arm, patients
will be assigned to the enrolling arm. Study has a new arm 3 and enrolling patients.
ARM I: Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles
repeat every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive olaparib PO twice daily (BID) on days 1-21 and adavosertib PO QD on
days 1-3 and 8-10. Cycles repeat every 21 days in the absence of disease progression or
Arm III: Patient receive ceralasertib tablets by PO BID each day on Days 1-14. You will also
take olaparib tablets by PO BID each day on Days 1-28.
After completion of study treatment, patients are followed up for 30 days and periodically
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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