This is a Phase II, randomized, multi-centre study aiming at comparing the efficacy of Olaparib and Cediranib vs. weekly Paclitaxel in terms of progression free survival (PFS) in platinum refractory or resistant recurrent ovarian cancer. Patients will be randomised in a 1:1:1 ratio to three treatment arms: * Arm A: Paclitaxel 80 mg/mq every week * Arm B: Cediranib 20 mg/day + Olaparib 600 mg / day (i.e. 300 mg BD) given every day * Arm C: Cediranib 20 mg/day given 5 days per weeks + Olaparib 600 mg / day (i.e. 300 mg BD) given 7 days per weeks
Both the experimental arms (Arm B and C) will be compared with Arm A in terms of PFS. If both superior to the control (Arm A), they will be compared in terms of gastrointestinal safety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
123
Comparator active compound
Experimental compound
Experimental compound
Spedali Civili di Brescia
Brescia, BS, Italy
Ospedale San Gerardo - ASST Monza
Monza, MB, Italy
Istituto Oncologico Veneto (IOV)
Padua, PD, Italy
Arcispedale Santa Maria Nuova
Reggio Emilia, RE, Italy
Efficacy: Progression Free Survival (PFS)
PFS is defined as time from randomization to the date of first progression or death for any cause, whichever comes first. Progression was established as the radiological disease progression according to RECIST 1.1 (as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions") or to clinical assessment in case radiological evaluation is not feasible due to clinical condition.
Time frame: An average of 30 months for each participant
Safety: Number of Evacuations Per Day
Number of evacuations per day used as an index of gastro-intestinal toxicity profile of experimental drugs
Time frame: Evacuation were collected daily for the first four weeks of treatment of experimental drugs
Efficacy: Objective Response Rate (ORR)
Percentage of patients with an objective response as determined by RECIST 1.1
Time frame: Disease assessments were scheduled every 8 weeks (+/- 1 week) from randomization for all treatment duration (an average of 3.5 months).
Efficacy: PFS2
PFS2 is defined as time from first progression to the date of second progression or death for any cause, whichever comes first.
Time frame: Up to one year after the last patient enrolled
Efficacy: Overall Survival (OS)
OS is defined as time from randomization to the date of death for any cause
Time frame: Up to one year after the last patient enrolled
Efficacy: Quality of Life
Quality of Life evaluated by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire
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Policlinico Umberto I - Università La Sapienza
Rome, RM, Italy
Istituto Eurpeo di Oncologia (IEO)
Milan, Italy
Time frame: Up to sixth month of study treatment
Safety: Maximum Toxicity Grade
Maximum toxicity grade experienced by each patient, for each toxicity, according to NCI-CTCAE v. 4.03
Time frame: Up to 30 days after the end of treatment
Safety: Number of Patients Experiencing Grade 3-4 Toxicity for Each Toxicity
Number of patients experiencing grade 3-4 toxicity for each toxicity according to NCI-CTCAE v. 4.03
Time frame: Adverse events were collected at the end of each cycle for the duration of treatment for each participant (an average of 3.5 months) and following 30 days after the end of treatment.
Safety: Type, Frequency and Nature of SAEs
Type, frequency and nature of SAEs, according to NCI-CTCAE v. 4.03
Time frame: Up to 30 days after the end of treatment
Safety: Number of Patients With at Least a SAE; Patients With at Least a SADR
Number of patients with at least a SAE; patients with at least a SADR, according to NCI-CTCAE v. 4.03
Time frame: Up to 30 days after the end of treatment
Safety: Number of Patients With at Least a SUSAR
Number of patients with at least a SUSAR, according to NCI-CTCAE v. 4.03
Time frame: Up to 30 days after the end of treatment
Compliance: Number of Administered Cycles
The endpoint for compliance is the number of administered cycles.
Time frame: Up to one year after the last patient enrolled
Compliance: Reasons for Discontinuation and Treatment Modification
The endpoints for compliance are the reasons for discontinuation and treatment modification.
Time frame: Up to one year after the last patient enrolled
Compliance: Dose Intensity
Entire dose administered during treatment
Time frame: Up to one year after the last patient enrolled