Trial Outcomes & Findings for Analysis of Olaparib Response in Patients With BRCA1 and/or 2 Promoter Methylation Diagnosed of Advanced Breast Cancer (NCT NCT03205761)

NCT ID: NCT03205761

Last Updated: 2024-10-18

Results Overview

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 according to RECIST v.1.1 (unless a progression, death or unacceptable toxicity is seen before the first tumor response assessment).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Through study treatment, and average of 8 weeks

Results posted on

2024-10-18

Participant Flow

Participant milestones

Participant milestones
Measure	Olaparib Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Overall Study STARTED	11
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Olaparib Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Overall Study Withdrawal by Subject	1
Overall Study Progressive Disease	10

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	51 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Spain	11 participants n=5 Participants
Menopause Status Postmenopausal	8 Participants n=5 Participants
Menopause Status Premenopausal	3 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 0	6 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 1	5 Participants n=5 Participants
Histopathologic type Ductal	8 Participants n=5 Participants
Histopathologic type Lobular	1 Participants n=5 Participants
Histopathologic type Not Available / Not Done	1 Participants n=5 Participants
Histopathologic type Adenoid Cystic Carcinoma	1 Participants n=5 Participants
Histologic grade Grade 1	1 Participants n=5 Participants
Histologic grade Grade 2	3 Participants n=5 Participants
Histologic grade Grade 3	7 Participants n=5 Participants
Status at Initial Diagnosis Without metastasis	7 Participants n=5 Participants
Status at Initial Diagnosis With metastasis	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through study treatment, and average of 8 weeks

Outcome measures

Outcome measures
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Overall Response Rate (ORR)	1 Participants

SECONDARY outcome

Timeframe: 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 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 according to RECIST v.1.1 (unless a progression, death or unacceptable toxicity is seen before the first tumor response assessment).

Outcome measures

Outcome measures
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Clinical Benefit Rate (CBR)	4 Participants

SECONDARY outcome

Timeframe: Through study treatment, up to 19 months

Population: There was only 1 Partial Response.

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 measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Olaparib n=1 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Response Duration (RD)	18.4 months

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Progression Free Survival (PFS)	1.8 months Interval 1.2 to 3.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Overall Survival (OS)	8.9 months Interval 1.2 to 13.7

SECONDARY outcome

Timeframe: 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, alkaline phosphatase, aspartate transaminase, alanine transaminase, urea/blood urea nitrogen, total protein, albumin and lactic dehydrogenase, urinalysis by dipstick, serum or urine pregnancy test, bone marrow or blood cytogenetic analysis. AEs were graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for AE) v. 4.03

Outcome measures

Outcome measures
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
The Number of Participants Who Experienced Adverse Events (AE) Related to Study Treatment	8 Participants

SECONDARY outcome

Timeframe: Through study treatment, and average of 8 weeks

Population: Only 4 patients with Partial Response or Stable Disease.

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.

Outcome measures

Outcome measures
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Correlation Value Between BRCA1 Methylation Status and Efficacy Outcome Data Patients with no Response: BRCA1 methylated	5 Participants
Correlation Value Between BRCA1 Methylation Status and Efficacy Outcome Data Patients with no Response: BRCA1 no methylated	2 Participants
Correlation Value Between BRCA1 Methylation Status and Efficacy Outcome Data Patients with Partial Response or Stable: BRCA1 methylated	4 Participants
Correlation Value Between BRCA1 Methylation Status and Efficacy Outcome Data Patients with Partial Response or Stable: BRCA1 no methylated	0 Participants

SECONDARY outcome

Timeframe: Through study treatment, and average of 8 weeks

Population: Only 4 patients with Partial Response or Stable Disease.

Outcome measures

Outcome measures
Measure	Olaparib n=11 Participants Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Correlation Value Between BRCA2 Methylation Status and Efficacy Outcome Data Patients with Partial Response or Stable : BRCA2 methylated	1 Participants
Correlation Value Between BRCA2 Methylation Status and Efficacy Outcome Data Patients with Partial Response or Stable : BRCA2 no methylated	3 Participants
Correlation Value Between BRCA2 Methylation Status and Efficacy Outcome Data Patients with no Response : BRCA2 methylated	3 Participants
Correlation Value Between BRCA2 Methylation Status and Efficacy Outcome Data Patients with no Response : BRCA2 no methylated	4 Participants

Adverse Events

Olaparib

Serious events: 4 serious events

Other events: 8 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Olaparib n=11 participants at risk Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
General disorders Progression Disease	36.4% 4/11 • Number of events 4 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.

Other adverse events

Other adverse events
Measure	Olaparib n=11 participants at risk Patients with a positive methylation status on at least one of the two genes and lacking of known deleterious or suspected deleterious mutations in both genes could be included in the study to receive olaparib tablet formulation at 600 mg total daily dose (given in two oral administrations of 300 mg every 12 hours approximately). Patients will continue to receive their treatment until objective disease progression, symptomatic deterioration, unacceptable toxicity, death or withdrawal of consent, whichever occurs first.
Blood and lymphatic system disorders Anaemia	9.1% 1/11 • Number of events 2 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Ear and labyrinth disorders Vertigo	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Gastrointestinal disorders Abdominal pain upper	18.2% 2/11 • Number of events 2 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Gastrointestinal disorders Constipation	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Gastrointestinal disorders Dyspepsia	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Gastrointestinal disorders Nausea	18.2% 2/11 • Number of events 2 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Gastrointestinal disorders Vomiting	18.2% 2/11 • Number of events 3 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
General disorders Asthenia	27.3% 3/11 • Number of events 3 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
General disorders Oedema peripheral	18.2% 2/11 • Number of events 2 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Investigations Haemoglobin	9.1% 1/11 • Number of events 2 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Metabolism and nutrition disorders Decreased appetite	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Musculoskeletal and connective tissue disorders Back pain	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.1% 1/11 • Number of events 2 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Nervous system disorders Headache	18.2% 2/11 • Number of events 2 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Psychiatric disorders Depressed mood	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Psychiatric disorders Insomnia	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Respiratory, thoracic and mediastinal disorders Orthopnoea	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Vascular disorders Hypertension	18.2% 2/11 • Number of events 5 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.
Vascular disorders Lymphoedema	9.1% 1/11 • Number of events 1 • AEs have been recorded through study treatment, an average of 8 weeks. Deaths were assessed up to 14 months. AE were reported after Informed Consent Document (ICD) and before study drugs until approximately 30 days following the discontinuation of study treatment.

Additional Information

Scientific Director / Medical Lead / Project Manager

Spanish Breast Cancer Research Group

Phone: +34916592870

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60