Best Approach in Recurrent-Ovarian-Cancer-with Cediranib-Olaparib

NCT03314740 | Completed Phase 2 Results DMC

• 1 other identifier: IRFMN-OVA-7289
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Ovarian Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  Evacuation were collected daily for the first four weeks of treatment of experimental drugs

Secondary Outcomes (12)

• Efficacy: Objective Response Rate (ORR)

  Disease assessments were scheduled every 8 weeks (+/- 1 week) from randomization for all treatment duration (an average of 3.5 months).

• Efficacy: PFS2

  Up to one year after the last patient enrolled

• Efficacy: Overall Survival (OS)

  Up to one year after the last patient enrolled

• Efficacy: Quality of Life

  Up to sixth month of study treatment

• Safety: Maximum Toxicity Grade

  Up to 30 days after the end of treatment

Study Arms (3)

Arm A

ACTIVE COMPARATOR

Intravenous administration of weekly Paclitaxel (dosage: 80 mg/mq) for a maximum of 6 cycles. Cycle is defined as 4 weeks.

Drug: Paclitaxel

Arm B

EXPERIMENTAL

Oral administration of two experimental drugs: * Cediranib 20 mg/day given 7 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death.

Drug: Cediranib; Drug: Olaparib

Arm C

EXPERIMENTAL

Oral administration of two experimental drugs: * Cediranib 20 mg/day given 5 days per week * Olaparib 600 mg / day (i.e. 300 mg twice a day) 7 days per week until progression, unacceptable toxicity, patient or physician decision to discontinue or death.

Drug: Cediranib; Drug: Olaparib

Interventions

Paclitaxel DRUG

Comparator active compound

Also known as: chemotherapy

Arm A

Cediranib DRUG

Experimental compound

Also known as: tyrosine kinase inhibitor

Arm B; Arm C

Olaparib DRUG

Experimental compound

Also known as: Parp inihibitor

Arm B; Arm C

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Patients affected by uro-genital neoplasm of ovary.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients affected by pathologically confirmed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Relapsed/progressive disease within 6 months from last platinum-based chemotherapy (platinum resistant/refractory disease).
• Any line of treatment (after the first).
• Any "last" chemotherapy line, including Paclitaxel, that should have been administered at least 6 months before the study beginning.
• Patients must be women \> 18 years of age.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥ 10.0 g/dL and no blood transfusions in the 28 days prior to entry/randomization - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• White blood cells (WBC) \> 3x109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional Upper Limit of Normal (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional Upper Limit of Normal, unless liver metastases are present in which case it must be ≤ 5x ULN
• Creatinine clearance estimated using the Cockcroft-Gault equation ≥51 mL/min,.
• ECOG performance status 0-1.
• Patients must have a life expectancy ≥ 16 weeks.
• Evidence of non-childbearing status for women of childbearing potential (negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1 or postmenopausal women. Postmenopausal status is defined as:

You may not qualify if:

• Any previous treatment with a PARP inhibitor, including Olaparib.
• Prior treatment with Cediranib (previous bevacizumab or other antiangiogenic drugs are allowed)
• Previous progression to weekly Paclitaxel
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years
• Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting Olaparib is 2 weeks.
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting Olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Persistent toxicities (\>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
• Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein \< 1.5g in a 24 hr period or urine protein/creatinine ratio \< 1.5.
• A history of poorly controlled hypertension or resting blood pressure \>150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy (measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2-minute intervals and averaged. If the first two diastolic readings differ by more than 5 mmHg, then an additional reading should be obtained and averaged).
• Blood transfusions within 28 days prior to study start.
• Features suggestive of Myelodysplastic syndrome or Acute myeloid leukemia (MDS/AML) on peripheral blood smear.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
• Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• AstraZeneca: collaborator

Study Sites (6)

Spedali Civili di Brescia

Brescia, BS, 25123, Italy

Location

Ospedale San Gerardo - ASST Monza

Monza, MB, 20900, Italy

Location

Istituto Oncologico Veneto (IOV)

Padua, PD, 35128, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, RE, 42123, Italy

Location

Policlinico Umberto I - Università La Sapienza

Rome, RM, 00161, Italy

Location

Istituto Eurpeo di Oncologia (IEO)

Milan, 20141, Italy

Location

Related Publications (2)

• Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.

  PMID: 35170751 DERIVED

• Colombo N, Tomao F, Benedetti Panici P, Nicoletto MO, Tognon G, Bologna A, Lissoni AA, DeCensi A, Lapresa M, Mancari R, Palaia I, Tasca G, Tettamanzi F, Alvisi MF, Rulli E, Poli D, Carlucci L, Torri V, Fossati R, Biagioli E; BAROCCO study group. Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer. Gynecol Oncol. 2022 Mar;164(3):505-513. doi: 10.1016/j.ygyno.2022.01.015. Epub 2022 Jan 19.

  PMID: 35063281 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Paclitaxel; Drug Therapy; cediranib; Tyrosine Kinase Inhibitors; olaparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Therapeutics; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Elena Biagioli
• Organization: Istituto di Ricerche Farmacologiche Mario Negri

elena.biagioli@marionegri.it

+39 0239014650

Study Officials

• Roldano Fossati, MD

  Mario Negri Institute for Pharmacological Research

  STUDY DIRECTOR

• Nicoletta Colombo, MD

  European Institute of Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: October 19, 2017
• Study Start: June 12, 2017
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: January 10, 2025
• Results First Posted: January 10, 2025

Record last verified: 2024-11

Locations

IT (6)