Multi-maintenance Olaparib After Disease Recurrence in Participants With Platinum Sensitive BRCAm High Grade Serous Ovarian Cancer

NCT02855697 | Completed Early Phase 1 DMC

• 1 other identifier: 15_DOG01_142
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

PARP inhibitors, such as olaparib, significantly improve progression free survival (PFS) in participants with recurrent, platinum-sensitive high-grade serous/endometrioid ovarian cancer (HGS/EOC), who harbour a germline mutation in BRCA 1 or 2 genes. Despite some of the most impressive hazard ratios seen in ovarian oncology, such improvements in PFS have not translated into improved overall survival (OS) advantage potentially because maintenance poly ADP ribose polymerase inhibitors (PARPi) are only being administered during a single remission. Here the investigators will test the feasibility of administering a second course of olaparib in participants who have recurrent platinum-sensitive HGS/EOC.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• To determine the feasibility of administering a second course of maintenance olaparib for more than 6 months (26 weeks) to participants with recurrent platinum-sensitive HGS/EOC who have been previously treated with olaparib.

  The proportion of participants who remain on olaparib for more than 6 months (26 weeks) in the second course of maintenance olaparib.

  6 months after the last patient has started the second course of olaparib

Secondary Outcomes (3)

• Impact of multi-maintenance olaparib treatment on time to first subsequent therapy (TFST) in participants with platinum sensitive recurrent BRCAm HGS/EOC.

  6 months after the last event

• Impact of multi-maintenance olaparib treatment on time to second subsequent therapy (TSST) in participants with platinum sensitive recurrent BRCAm HGS/EOC.

  6 months after the last event

• Progression-free survival (PFS) for each course of chemotherapy followed by olaparib

  6 months after the last event

Other Outcomes (1)

• To evaluate the feasibility of obtaining fresh tissue biopsies before each course of platinum chemotherapy, where the intention is to maintain platinum-induced clinical benefit with olaparib.

  6 months after the last patient starts the second course of olaparib.

Study Arms (1)

Olaparib +/- cediranib

EXPERIMENTAL

Patients are administered two courses of maintenance olaparib following chemotherapy. It is possible for patients to take cediranib during the second course of olaparib if recommended as per the protocol.

Drug: Olaparib; Drug: Cediranib; Drug: Platinum-based Chemotherapy

Interventions

Olaparib DRUG

300 mg taken twice daily, equivalent to a total daily dose of 600 mg

Also known as: Lynparza, AZD2281, KU-0059436

Olaparib +/- cediranib

Cediranib DRUG

20mg dose of cediranib was selected for this study

Also known as: AZD2171

Olaparib +/- cediranib

Platinum-based Chemotherapy DRUG

1 or 2 two courses of platinum-based chemotherapy administered depending on trial entry point.

Olaparib +/- cediranib

Eligibility Criteria

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

You may qualify if:

• Progressive, measureable high grade serous or endometrioid ovarian cancer, fallopian tube or primary peritoneal cancer
• Participants who have not been treated with PARP inhibitor previously will be treated with two maintenance courses of olaparib.
• Participants, who have received one course of maintenance olaparib before entry to the trial, will only receive one further course of treatment.
• Aged 18 or over
• Measureable disease by RECIST 1.1
• ECOG performance status 0-2 and life expectancy of over 12 weeks
• Adequate haematological function: Hb ≥ 10.0 g/l, Neutrophils ≥ 1.5 x 109/l, Platelets ≥ 100 x 109/l; coagulation: INR \<1.4 (unless therapeutically anti-coagulated) and/or APPT ratio \<1.4
• Adequate liver function: bilirubin ≤1.5 x ULN, Transaminases (ALT and AST) ≤2.5x ULN unless liver metastases are present in which case they must be ≤ 5x ULN
• Adequate renal function defined as GFR ≥ 51ml/min
• Written, informed consent that includes genetic research on tissue derived from biopsies.
• Pathogenic germline BRCA-1 or -2 gene mutation
• Ability to swallow oral medication (tablets).

You may not qualify if:

• Concurrent medical illness that would impact on compliance with the protocol including MDS/ AML
• Uncontrolled brain metastases or seizures. A scan to confirm the absence of brain metastases is not required.
• Known positivity for Hep B, Hep C or HIV.
• Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• 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.
• Another cancer, which has been active within the previous 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and no evidence of recurrence of other malignancy.
• Female participants who are able to become pregnant (or are already pregnant or lactating) unless the following apply: Those who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for one month afterwards are considered eligible. Alternatively if the participant can abstain from sexual intercourse for the same interval, then they are eligible to participate.
• Participants who are planning to receive maintenance bevacizumab.
• Participants will be excluded if the side effects of previous treatments have not resolved to grade I or less, with the exception of alopecia or grade 2 neurotoxicity that is considered related to cytotoxic chemotherapy.
• Radiotherapy, surgery or tumour embolization within 28 days before the cycle 1 day 1 of the platinum-containing chemotherapy.
• Additional concurrent anti-cancer therapy.
• Causes of malabsorption e.g. uncontrolled diarrhoea or poorly controlled stoma is not permitted.
• Participants who have contra-indications to VEGF inhibitors will not be eligible to receive cediranib (second treatment). These contra-indications include concurrent or past history of malignant fistula, uncontrolled hypertension, recent arterial thrombosis (cerebrovascular accident or myocardial infarction) within the past 6 months, participants who are at risk of bowel perforation, proteinuria greater than 2g/24 hours or a past history of VEGF inhibitor-associated reversible posterior leukoencephalopathy.
• Any participant that is participating in another interventional clinical trial within 30 days or 5-lives prior to signing of consent. Participation in an observational trial would be acceptable.

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Clinical Trials Unit, Manchester: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

olaparib; cediranib; Platinum Compounds

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)

Inorganic Chemicals

Study Officials

• Gordon Jayson, MD, Prof.

  The Christie National Health Service (NHS) Foundation Trust

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: August 4, 2016
• Study Start: May 26, 2017
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 22, 2022

Record last verified: 2022-02

Locations

GB (1)