Olaparib Tablets Maintenance Monotherapy Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

NCT03534453 | Completed Phase 3

• 1 other identifier: D0816C00016
• Study Type: interventional
• Target: 229
• Locations: 2 countries
• Sites: 25

Brief Summary

This is a prospective, open-label, single arm, multi-centre interventional study to assess the clinical efficacy and safety of olaparib maintenance monotherapy and will be conducted in patients with platinum sensitive relapsed (PSR) high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy

Conditions

Relapsed Ovarian Cancer; Following Complete or Partial Response to Platinum Based Chemotherapy; Platinum Sensitive

Keywords

ovarian cancer; PARP Inhibitor; Platinum sensitive

Outcome Measures

Primary Outcomes (1)

• Time from first dosing date of olaparib to date of disease progression or death from any cause (if this occurs before disease progression)

  Progression free survival (using investigator assessment) according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1) of olaparib tablets maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy

  from first dosing date until objective radiological disease progression by RECIST 1.1, or death from any cause, whichever come first, assessed 45 months.

Secondary Outcomes (6)

• Time from first dosing date of olaparib to date of disease progression or death from any cause (if this occurs before disease progression)

  from first dosing date until objective radiological disease progression by RECIST 1.1, or death from any cause, whichever come first, assessed 45 months.

• Time from first dosing date of olaparib to date of death from any cause

  from first dosing date to death, assessed 45 months.

• Time from first dosing date of olaparib to date of second progression event or death from any cause (if this occurs before second progression event)

  from first dosing date to second progression, or death from any cause, whichever come first, assessed 45 months.

• Time from first dosing date of olaparib to date of first subsequent treatment commencement or death from any cause (if this occurs before commencement of first subsequent treatment)

  Time from first dosing date of olaparib to date of first subsequent treatment commencement or death from any cause (whichever earlier), assessed 45 months.

• Time from first dosing date of olaparib to date of second subsequent treatment commencement or death from any cause (if this occurs before commencement of second subsequent treatment)

  Time from first dosing date of olaparib to date of second subsequent treatment commencement or death from any cause (whichever earlier), assessed 45 months.

Other Outcomes (5)

• AEs/SAEs

  AEs and SAEs collected from informed consent until post treatment 30-day follow-up period, assessed 45 months.

• clinical chemistry/haematology parameters.

  assessment until post treatment 30-day follow-up period, assessed 45 months.

• Immune-markers PD-L1 expression in tumor tissues

  PD-L1 expression in tumor tissues before olaparib treatment.

Study Arms (1)

Olaparib 300mg tablets

EXPERIMENTAL

Taken orally twice daily

Drug: Olaparib 300mg tablets

Interventions

Olaparib 300mg tablets DRUG

300mg Olaparib tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Olaparib 300mg tablets

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Age 18 years or over
• Patients with platinum sensitive relapsed high grade (serous or endometrioid) epithelial ovarian cancers (including primary peritoneal and/or fallopian tube cancer)
• Platinum sensitive disease is defined as disease progression ≥6 months after completion of their last dose of platinum based chemotherapy
• Patients should have received at least 2 previous lines of platinum containing therapy prior to enrolment:
• For the last chemotherapy course immediately prior to enrolment on the study, patients must be, in the opinion of the investigator, in response (partial or complete radiological response according to RECIST 1.1 criteria) and no evidence of a rising CA-125, following completion of this chemotherapy course.
• Have availability of 10 ml blood for germline BRCA testing and tumor sample for sBRCA and HRRm testing: paraffin-embedded archived tumor tissue block (preferred) or, if a block is not possible, it would be better to have qualified 15 5-μm unstained sections.
• 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 with no blood transfusions in the past 28 days
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN
• Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min:
• Estimated creatinine clearance =\[(140-age \[years\]) x weight (kg)\]/\[serum creatinine (mg/dL) x 72\] (x F)a

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrolment in the present study
• Participation in another clinical study with an investigational product during the most recent chemotherapy course
• Any previous treatment with PARP inhibitor, including olaparib
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years. Patients with a history of localised triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• 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 (\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• 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 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Major surgery within 2 weeks of starting study treatment, or patients have not recovered from any effects of any major surgery.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (25)

Research Site

Beijing, 100142, China

Location

Research Site

Changsha, 410013, China

Location

Research Site

Chengdu, 610041, China

Location

Research Site

Chongqing, 400030, China

Location

Research Site

Chongqing, 400038, China

Location

Research Site

Hangzhou, 310006, China

Location

Research Site

Hangzhou, 310022, China

Location

Research Site

Harbin, 150081, China

Location

Research Site

Hefei, 230031, China

Location

Research Site

Jinan, 250012, China

Location

Research Site

Shanghai, 200011, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Shanghai, 200080, China

Location

Research Site

Shenyang, 110016, China

Location

Research Site

Tianjin, 300060, China

Location

Research Site

Tianjin, 300100, China

Location

Research Site

Wuhan, 430030, China

Location

Research Site

Wuhan, 430079, China

Location

Research Site

Xi'an, 710061, China

Location

Research Site

Zhengzhou, 450008, China

Location

Research Site

Ampang, 68000, Malaysia

Location

Research Site

Johor Bahru, 81100, Malaysia

Location

Research Site

Kuala Lumpur, 59100, Malaysia

Location

Research Site

Kuching, 93586, Malaysia

Location

Research Site

Putrajaya, 62250, Malaysia

Location

Related Publications (2)

• Li H, Peng Z, Zhu J, Zhao W, Huang Y, An R, Zheng H, Qu P, Wang L, Zhou Q, Wang D, Lou G, Wang J, Wang K, Kong B, Xie X, Yin R, Low J, Rozita AM, Sen LC, Meng YC, Kiong KS, Liu J, Liang Z, Lv W, Zhu Y, Hu W, Sun W, Su J, Wang Q, Zang R, Ma D, Gao Q. Exploratory biomarker analysis in the phase III L-MOCA study of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer. BMC Med. 2024 May 16;22(1):199. doi: 10.1186/s12916-024-03409-9.

  PMID: 38755585 DERIVED

• Gao Q, Zhu J, Zhao W, Huang Y, An R, Zheng H, Qu P, Wang L, Zhou Q, Wang D, Lou G, Wang J, Wang K, Low J, Kong B, Rozita AM, Sen LC, Yin R, Xie X, Liu J, Sun W, Su J, Zhang C, Zang R, Ma D. Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA). Clin Cancer Res. 2022 Jun 1;28(11):2278-2285. doi: 10.1158/1078-0432.CCR-21-3023.

  PMID: 35131903 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

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

Study Officials

• Ding MA, PhD

  Tongji Hospital, Tongji Medical College of Huazhong University of Sicence and Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: May 23, 2018
• Study Start: May 29, 2018
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (20); MY (5)