Efficacy of Olaparib in Advanced Cancers Occurring in Patients With Germline Mutations or Somatic Tumor Mutations in Homologous Recombination Genes

NCT03967938 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: Precision 2 - Olaparib
• Study Type: interventional
• Target: 540
• Locations: 1 country
• Sites: 1

Brief Summary

At present targeted therapy with the PARP inhibitor olaparib has become standard of care in advanced platinum sensitive BRCA1/2 mutant ovarian cancer. The key in this sensitivity is the loss of homologous recombination (HR) function. The current project aims to treat patients with any type of cancer carrying in their germline a mutation in genes that generate such an homologous recombination deficiency (HRD) or have an acquired somatic mutation in their tumor with the targeted PARP inhibitor olaparib. The project would thus bring access to a targeted drug matched to the genomic profile of the tumor of these patients and provide oncologists with information regarding efficacy and safety of olaparib in these patients. This evidence could then later lead to a more routine regulatory access.

Conditions

Advanced Cancers Harbouring Mutations in HRG

Outcome Measures

Primary Outcomes (2)

• Response rate according to RECIST 1.1

  The primary analysis will estimate the proportion of patients who achieve confirmed objective response according to the RECIST criteria. Objective response is defined as confirmed CR or PR.

  every 2 months from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Response duration according to RECIST 1.1

  Patients whose best RECIST assessment is stable disease, partial, or complete response will be considered to have achieved disease control. Descriptive statistics will be produced for the duration of confirmed objective response and disease control.

  from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (3)

• locus-specific LOH

  through study completion, an average of 1 year

• PFS

  every 2 months from date of randomization until teh date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

• OS

  every 2 months from date of randomization until teh date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

Study Arms (1)

Olaparib

EXPERIMENTAL

tablets of 300mg twice daily until disease progression

Drug: Olaparib Oral Capsule

Interventions

Olaparib Oral Capsule DRUG

Olaparib tablets 300mg twice daily

Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• 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
• Female or male aged \> 18 years
• Histologically proven advanced cancer, either locally or metastatic, harboring a specific pathogenic genetic alteration (with the exception of breast, pancreas, or prostate cancer patients harboring a BRCA1/2 mutation and HRD ovarian cancer)
• No approved targeted therapy for the specific genetic alteration in the specific tumor type
• No other genomic driven phase I, II or III trial available for the specific genomic alteration in the specific tumor type
• Available tumor tissue for verification of the mutation by Sanger sequencing.
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients must have a life expectancy ≥16 weeks
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT and is suitable for repeated assessment.
• \*Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for local genetic testing.

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)
• Ovarian cancer patients harboring a HRD and breast, prostate and pancreas cancer patients who carry a BRCA1/2 mutation
• Previous enrolment in the present study
• Participation in another clinical study with an investigational product during the last 4 weeks or radiotherapy (except for palliative reasons) within three weeks prior to study treatment.
• History of non-compliance to medical regimens
• 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 localized 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 indicating uncontrolled, potentially reversible cardiac conditions as judged by the investigator (er., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>500ms, electrolyte disturbances, etc.) or patients with congenital long QT syndrome
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within four weeks prior to study treatment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
• 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 and patients must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• AZ-VUB: lead
• AstraZeneca: collaborator
• Kom Op Tegen Kanker: collaborator

Study Sites (1)

UZ Brussel

Brussels, 1090, Belgium

Location

MeSH Terms

Interventions

olaparib

Study Officials

• Sofie Joris, Dr

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinator Investigator

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: May 30, 2019
• Study Start: February 7, 2019
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)