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NCT03205761: COMETABreast

Analysis of Olaparib Response in Patients With BRCA1 and/or 2 Promoter Methylation Diagnosed of Advanced Breast Cancer

Completed Phase 2 Results posted Last updated 18 October 2024
What this trial tests

Phase 2 trial testing Olaparib in Advanced Breast Cancer in 11 participants. Completed in 15 December 2022.

Timeline
23 October 2017
Primary endpoint
15 December 2022
15 December 2022

Quick facts

Lead sponsorSpanish Breast Cancer Research Group
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment11
Start date23 October 2017
Primary completion15 December 2022
Estimated completion15 December 2022
Sites16 locations across Spain

Drugs / interventions tested

Conditions studied

Sponsor

Spanish Breast Cancer Research Group

Who can join

18 and older, female only, with Advanced Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) Primary · Through study treatment, and average of 8 weeks

ORR is defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) out of the patients from the efficacy population. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an \>=30% decrease in the sum of the longest diameter of target lesions. Tumor response will be assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1). Efficacy population is a subset of the intend to treat population that has received at least one dose of study medication and has performed at least one tumor response assessment acco

GroupValue95% CI
Olaparib1
Clinical Benefit Rate (CBR) Secondary · Through study treatment, and average of 8 weeks

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CBR was defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR) plus stable disease (SD) ≥ 24 weeks out of the efficacy population. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an \>=30% decrease in the sum of the longest diameter of target lesions; SD is defined as a failure to meet criteria for CR or PR in the absence of progressive disease. Overall Response (OR) = CR + PR. Efficacy population is a subs

GroupValue95% CI
Olaparib4
Response Duration (RD) Secondary · Through study treatment, up to 19 months

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. RD was defined as the time from the first documentation of objective tumor response (complete response (CR) or partial response (PR)) to the first documented progressive disease (PD), or to death due to any cause, whichever occurs first. Per RECIST, CR is defined as the disappearance of all target lesions; PR is defined as an \>=30% decrease in the sum of the longest diameter of target lesions; PD is defined as a 20% increase in the sum of the longest diameter of target lesions, or a

GroupValue95% CI
Olaparib18.4
Progression Free Survival (PFS) Secondary · Through study treatment, and average of 8 weeks

Tumor response was assessed using Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1). PFS is defined as the time from enrollment to the first documented progression disease (PD), or death from any cause, whichever occurs first. PD is defined using RECIST, 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.

GroupValue95% CI
Olaparib1.81.2 – 3.7
Overall Survival (OS) Secondary · Up to 14 months

Overall Survival (OS) defined as the time from the date of study enrollment to the date of death from any cause.

GroupValue95% CI
Olaparib8.91.2 – 13.7
The Number of Participants Who Experienced Adverse Events (AE) Related to Study Treatment Secondary · Through study treatment, and average of 8 weeks

Safety assessments were performed at baseline and during the study: blood pressure, pulse, body temperature, performance status evaluation, 12-lead electrocardiogram, hemoglobin, red blod cells, platelet, mean cell volume, mean cell haemoglobin concentration, mean cell haemoglobin, white blood cells, absolute differential white cell count, absolute neutrophil count or segmented neutrophil count and band forms, activated partial thromboplastin time, international normalised ratio, sodium, potassium, calcium, magnesium, fasting glucose, creatinine, total bilirubin, gamma glutamyltransferase, alk

GroupValue95% CI
Olaparib8
Correlation Value Between BRCA1 Methylation Status and Efficacy Outcome Data Secondary · Through study treatment, and average of 8 weeks

To evaluate the effect of methylation status with efficacy rate parameters it will be used chi-square test if both of them are quantitative, and will be used an ANOVA analysis if one variable is quantitative and the other one is qualitative.

Patients with no Response: BRCA1 methylated
GroupValue95% CI
Olaparib5
Patients with no Response: BRCA1 no methylated
GroupValue95% CI
Olaparib2
Patients with Partial Response or Stable: BRCA1 methylated
GroupValue95% CI
Olaparib4
Patients with Partial Response or Stable: BRCA1 no methylated
GroupValue95% CI
Olaparib0
Correlation Value Between BRCA2 Methylation Status and Efficacy Outcome Data Secondary · Through study treatment, and average of 8 weeks

To evaluate the effect of methylation status with efficacy rate parameters it will be used chi-square test if both of them are quantitative, and will be used an ANOVA analysis if one variable is quantitative and the other one is qualitative.

Patients with Partial Response or Stable : BRCA2 methylated
GroupValue95% CI
Olaparib1
Patients with Partial Response or Stable : BRCA2 no methylated
GroupValue95% CI
Olaparib3
Patients with no Response : BRCA2 methylated
GroupValue95% CI
Olaparib3
Patients with no Response : BRCA2 no methylated
GroupValue95% CI
Olaparib4

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Olaparib
Serious: 4/11 (36%)
Deaths: 8/11

Serious adverse events (1 terms)

ReactionSystemOlaparib
Progression DiseaseGeneral disorders
Other adverse events (21 terms — click to expand)

ReactionSystemOlaparib
AstheniaGeneral disorders
Abdominal pain upperGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
HeadacheNervous system disorders
HypertensionVascular disorders
AnaemiaBlood and lymphatic system disorders
VertigoEar and labyrinth disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
HaemoglobinInvestigations
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Depressed moodPsychiatric disorders
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
OrthopnoeaRespiratory, thoracic and mediastinal disorders
LymphoedemaVascular disorders

Most-reported serious reactions: Progression Disease.

Data from ClinicalTrials.gov NCT03205761 adverse events section.

Sponsor's own description

This is a multicenter single-arm phase II clinical trial to evaluate the efficacy and safety of olaparib in patients diagnosed of advanced triple negative breast cancer (TNBC) with methylation of BRCA1 and/or BRCA2 promoters assessed in DNA from metastatic lesions and absence of BRCA1 and 2 germline mutations.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment.
    Garrido-Castro AC, Lin NU, Polyak K. · · 2019 · cited 1061× · PMID 30679171 · DOI 10.1158/2159-8290.cd-18-1177
  2. An Overview of PARP Inhibitors for the Treatment of Breast Cancer.
    Cortesi L, Rugo HS, Jackisch C. · · 2021 · cited 263× · PMID 33710534 · DOI 10.1007/s11523-021-00796-4
  3. DNA Repair Pathways in Cancer Therapy and Resistance.
    Li LY, Guan YD, Chen XS, Yang JM, et al · · 2020 · cited 254× · PMID 33628188 · DOI 10.3389/fphar.2020.629266
  4. A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation.
    Castroviejo-Bermejo M, Cruz C, Llop-Guevara A, Gutiérrez-Enríquez S, et al · · 2018 · cited 238× · PMID 30377213 · DOI 10.15252/emmm.201809172
  5. The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade glioma treated in EORTC 22033.
    Bady P, Kurscheid S, Delorenzi M, Gorlia T, et al · · 2018 · cited 76× · PMID 29368212 · DOI 10.1007/s00401-018-1810-6
  6. Cell-Free DNA Fragmentomics: A Promising Biomarker for Diagnosis, Prognosis and Prediction of Response in Breast Cancer.
    Gianni C, Palleschi M, Merloni F, Di Menna G, et al · · 2022 · cited 26× · PMID 36430675 · DOI 10.3390/ijms232214197
  7. Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.
    Kaur P, Porras TB, Ring A, Carpten JD, et al · · 2019 · cited 20× · PMID 30728399 · DOI 10.1038/s41598-018-37574-8
  8. BRCAness as an Important Prognostic Marker in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy: A Multicenter Retrospective Study.
    Kosaka Y, Yamamoto Y, Tanino H, Nishimiya H, et al · · 2020 · cited 4× · PMID 32098267 · DOI 10.3390/diagnostics10020119

Verify or expand the search:

Other trials of Olaparib

Trials testing the same drug.

Other recruiting trials for Advanced Breast Cancer

Currently open trials in the same condition.

Other Spanish Breast Cancer Research Group trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03205761.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing