Olaparib +/- Cediranib or Chemotherapy in Patients With Platinum-resistant Ovarian Cancer

NCT03117933 | Completed Phase 2

• 3 other identifiers: OCTO_0622016-000559-2816/LO/2150
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 14

Brief Summary

The trial will compare the drugs olaparib and cediranib with standard chemotherapy in platinum resistant ovarian cancer. Patients will be randomised to one of three treatment groups: olaparib only, olaparib and cediranib and the control group paclitaxel. The aim is to compare efficacy of the 3 treatments and also how well each treatment is tolerated including the participants quality of life.

Conditions

Ovarian Cancer

Keywords

BRCA1/2 mutation; Platinum resistance

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival (PFS), measured as time from date of randomisation to RECIST-defined progression or death from any cause (whichever is first)

  up to 18 months

Secondary Outcomes (7)

• Adverse events

  up to 18 months

• Overall Survival

  12 & 18 months

• Objective Response Rate

  up to 18 months

• Objective Response Rate

  up to 18 months

• Quality of Life Outcomes

  up to 18 months

Study Arms (3)

A: Paclitaxel

ACTIVE COMPARATOR

Paclitaxel, IV weekly, 80mg/m2; until progression

Drug: Paclitaxel

B: Olaparib

EXPERIMENTAL

Olaparib, oral, 300mg twice daily; until progression

Drug: Olaparib

C: Olaparib and Cediranib

EXPERIMENTAL

Olaparib, oral, 300mg twice daily and Cediranib, tablet, 20mg once daily; until progression

Drug: Olaparib; Drug: Cediranib

Interventions

Olaparib DRUG

Tablet, 100mg and 150mg

B: Olaparib; C: Olaparib and Cediranib

Cediranib DRUG

Tablet 15mg and 20mg

C: Olaparib and Cediranib

Paclitaxel DRUG

Intravenous (IV)

A: Paclitaxel

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients, age ≥ 16 years with relapsed epithelial ovarian, primary peritoneal or fallopian tube cancer who have relapsed within 12 months of previous platinum-based therapy. Their most recent chemotherapy does not have to have been platinum-based.
• Patients can have received prior PARP inhibitor, but there must be a \> 6 month interval since treatment.
• Patients can have received prior antiangiogenic therapy, but there must be a \> 6 month interval since treatment; except for bevacizumab where a 6 week interval is required.
• Measurable disease by RECIST Version 1.1 performed in past 4 weeks. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
• Sufficient archival tissue confirming histological diagnosis available.
• ECOG PS 0-2
• Able to swallow and retain oral medications.
• Life expectancy \> 12 weeks in terms of disease related mortality
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Written (signed and dated) informed consent prior to any study specific procedures and be capable of co-operating with protocol.
• Patients must have
• Haemoglobin ≥ 9.0 g/dL and no blood transfusions in the 28 days prior to randomisation
• Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count \> 100 x 109/L

You may not qualify if:

• Received previous single agent weekly paclitaxel for relapsed disease.
• Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used during the trial and for 6 months after stopping treatment. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Pregnancy test will be performed monthly in women of child bearing potential.
• Postmenopausal is defined as:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• LH and FSH levels in the post-menopausal range for women under 50,
• radiation-induced oophorectomy with last menses \>1 year ago,
• chemotherapy-induced menopause with \>1 year interval since last menses, or surgical sterilisation (bilateral oophorectomy or hysterectomy).
• Treatment with any other investigational agent, systemic chemotherapy, or participation in another interventional clinical trial within 28 days prior to enrolment.
• Radiotherapy within 2 weeks from the last dose prior to study treatment
• Started a stable dose of bisphosphonates for bone metastases less than 4 weeks prior to treatment with study drug e.g. patient is eligible and can continue to take bisphosphonates if these were started at least 4 weeks prior to treatment with study drug.
• Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
• Concomitant use of potent inducers of CYP3A4 such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John Wort.
• Persistent toxicities (\>=CTCAE grade 2) caused by previous cancer therapy with the exception of alopecia.
• Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
• Blood transfusions within 1 month prior to study start

Sponsors & Collaborators

• University of Oxford: lead
• AstraZeneca: collaborator

Study Sites (14)

Belfast City Hospital

Belfast, County Antrim, BT9 7AM, United Kingdom

Location

Mount Vernon Cancer Centre

Northwood, Middlesex, United Kingdom

Location

City Hospital Nottingham

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Royal Surrey County Hospital

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Royal United Hospital

Bath, United Kingdom

Location

Velindre

Cardiff, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

St Bartholomew's

London, EC1A 7BE, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Royal Marsden Chelsea & Sutton

London, United Kingdom

Location

University College London

London, United Kingdom

Location

The Christie

Manchester, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (2)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

• Mansouri A, McGregor N, Dunn R, Dobbie S, Holmes J, Collins L, Nicum S. Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol. BMJ Open. 2021 Jan 15;11(1):e041463. doi: 10.1136/bmjopen-2020-041463.

  PMID: 33452192 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib; cediranib; Paclitaxel

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

Study Design

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

Model Details: Randomised open label trial with 3 arms, stratified for prior PARP use, prior anti-angiogenic use and BRCA status.

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: April 18, 2017
• Study Start: March 9, 2017
• Primary Completion: March 12, 2021
• Study Completion: December 31, 2023
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (14)