Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Pembrolizumab

Albumin-Bound Paclitaxel

Olaparib

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

1. Neoadjuvant phase; Treatment 1: Pembrolizumab+ Paclitaxel + Carboplatin (Cycles 1-4) Treatment 2: Pembrolizumab + Olaparib (Cycles 1-4)
2. Definitive Surgery
3. Adjuvant phase; Pembrolizumab + Olaparib (1-9 cycles)

Note: each cycle = 3 weeks (Neoadjuvant Treatment 1 and 2, and Adjuvant Treatment)

200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4

80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4

Area under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles 1-4

Each subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant treatment.

Definitive Surgery

Yuko Takahashi, MD., PhD.

Hironobu TAN, PhD.

Masaya Hattori, MD., PhD.

Kumiko Kida, MD., PhD.

This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for germline BRCA (gBRCA) 1/2 mutated triple negative breast cancer (TNBC).

Pembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be studied

Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer

Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B/OPERETTA)

Pathological complete response rate (ypT0/TisypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.

Residual Cancer Burden (RCB) 0/1 rate is defined as the proportion of subjects on evaluation from routine pathologic sections of the primary breast tumor and the regional lymph nodes after the completion of neoadjuvant therapy assessed by the local pathologist at the time of definitive surgery. Six variables are included in a calculation formula. The calculated RCB index value can also be categorized as one of four RCB classes (0 - 3). The calculation formula and detailed description can be found at a dedicated Web site: http://www.mdanderson.org/breastcancer_RCB.

Pathological complete response rate (ypT0/is) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen regardless of regional lymph nodes status following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.

The Proportion of Three Year-Overall Survival (3y-OS) is defined as the proportion of survival subjects without death due to any cause at 3 years from registration. Subjects without documented death at the time of the analysis will be censored at the date of the last follow-up.

The Proportion of Three-Year Distant Metastatic Free Survival (3y-DMFS) is defined as the proportion of survival subjects without distant metastatic disease at 3 years from registration. Subjects without documented distant metastatic disease at the time of the analysis will be censored at the date of the last follow-up.

The Proportion of Three-Year Disease Free Survival (3y-DFS) is defined as the proportion of survival subjects without metastatic disease and secondary malignancy at 3 years from registration. Subjects without documented metastatic disease and secondary malignancy at the time of the analysis will be censored at the date of the last follow-up.

Safety measurements are the incidence of, causality of, and outcome of AEs/SAEs; and changes in vital sign measurements and laboratory values.

Merck Sharp & Dohme LLC

Okayama University

Assistant professor, Endocrinological Center

Standard mammography

Standard mammography and tomosynthesis

cedric De Bazelaire, MD PHD

Matthieu Resche-Rigon, MD PHD

matthieu resche-rigon

Isabelle THOMASSIN- NAGGARA, Pr

Tomosynthesis is an innovative technique developed in digital mammography for obtaining a sectional image of the breast. Mammography has the main disadvantage of being an imaging projection that creates overlays, which eliminates tomosynthesis.

The objective of this study is to evaluate if the BI-RADS classification obtained by tomosynthesis with synthetic mammography is superior to that obtained by conventional mammography in terms of specificity while not inferior in terms of sensitivity.

Evaluation of Tomosynthesis for Characterization and the Management of Breast Lesions

EVALUATION DE LA TOMOSYNTHESE DANS LA CARACTERISATION ET LA PRISE EN CHARGE DES LESIONS MAMMAIRES : "ETOLE"

The primary evaluation parameter will be the classification error of tumors according to the BiRads scale obtained by mammography (BiRadsM) and by tomosynthesis (BiRadsT) according to the gold standard.

The visibility (presence or absence) of signs of poor prognosis criteria. We will compare the visibility of poor prognosis criteria seen on mammography + ultrasound and seen on tomosynthesis with synthetic mammography + ultrasound.

Needs for supplementary breast imaging exams and biopsies

The reproducibility of the interpretation of tomosynthesis will be assessed with differences of classifications BiRadsT observed between the two radiologists

Cumulative incidence of Breast cancer diagnosis among women with benign at after primary evaluation

Assistance Publique - Hôpitaux de Paris

Participants will receive two 50 mg capsules in the morning and two 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.

Participants will receive eight 50 mg capsules in the morning and eight 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.

Participants will receive capsules of olaparib orally as stated in arm description.

James Carmichael, BSc, MBChB, MD, FRCP

Andrew Tutt, PhD MRCP FRCR

The purpose of the study is to see if the drug KU-0059436 (olaparib) is effective and well tolerated in treating participants with measurable breast cancer gene (BRCA)1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists.

This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1- or BRCA2- associated breast cancer. Two sequential participant cohorts will receive continuous oral olaparib in 28-day cycles. The first cohort will receive 400 mg bd and the second cohort will receive 100 mg bd.

Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer

A Phase II, Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU-0059436 Given Orally Twice Daily in Patients With Advanced BRCA1- or BRCA2-associated Breast Cancer.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The ORR is the percentage of participants whose best tumor response is either complete response (CR) or partial response (PR), according to the RECIST v1.0 criteria. The CR is defined as disappearance of all target lesions (TLs). The PR is defined as at least a 30% decrease in the sum of longest diameters (LD) taking as reference the baseline sum of LD. Percentage of participants with ORR is reported.

Duration of response is defined as the date of progression per RECIST criteria - the date when CR or PR \[whichever is earliest\] is confirmed + 1. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Duration of response was analyzed for those participants who had OR.

The CBR is defined as the percentage of participants with a RECIST tumor response of confirmed CR, PR or stable disease (SD) for ≥ 8 weeks +/- 1 week visit window. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum of LD since the treatment started.

The tumor size is defined as the sum of the longest diameters as measured among all target lesions. At each assessment, the percentage change in tumor size is defined as 100 × 1 - (sum of all target lesion diameters at visit/sum of all target lesion diameters at baseline).

PFS is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression. Those participants who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where participants had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment. PFS was analyzed using Kaplan-Meier estimate.

ECOG performance status is used by researchers to assess how a participant's disease is progressing. The scores are: 0=Fully Active, able to carry out work without restrictions; 1=Restricted activity and able to carry out light work or sedentary nature; 2=capable of self-care but unable to carry out work activities; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely Disabled, and totally confined to bed or chair; 5=Dead. Change in ECOG performance status was defined as improved (less than the baseline value), no change (same as at baseline), worsened (greater than the baseline value) or missing (score is missing or was not recorded at baseline). If no measurement was recorded at Cycle 1 Day 1, the change was calculated in relation to the last recorded ECOG value prior to Day 1.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Number of participants with clinically significant changes in vital signs are reported. Vital sign parameters included body temperature, blood pressure, and pulse rate.

Number of participants with at least 2-grade change from baseline to worst toxicity grade in clinical laboratory parameters are reported. Laboratory parameters included hematology, clinical chemistry, and urinalysis.

KuDOS Pharmaceuticals Limited

AstraZeneca

Safety population included all participants who received at least one dose of study drug.

Participants received two 50 mg capsules in the morning and two 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion was met.

Olaparib 100 mg

Participants received eight 50 mg capsules in the morning and eight 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion was met.

Olaparib 400 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The full analysis set comprised of all enrolled participants with positive BRCA status, who took at least one dose of investigational medicinal product irrespective of whether they completed the trial schedule and IMP regime or not.

The plasma concentration data was analysed using a population approach and polyadenosine 5' diphosphoribose polymerase (PARP) inhibition data had already been obtained from Study D0810C00002. Hence no pharmacokinetic and PARP inhibition data are included.

Global Clinical Lead

The per-protocol (PP) population included all enrolled participants who completed the trial schedule and medication regime without any major deviations to the protocol.

Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

The PP population included all enrolled participants who completed the trial schedule and medication regime without any major deviations to the protocol.

Duration of Response (DoR) to Olaparib

Clinical Benefit Rate (CBR)

Best Percentage Change in Tumor Size

Progression-free Survival (PFS)

Cycle 7 Day 1

Withdrawal visit

Number of Participants With Improvement in Eastern Co-operative Oncology Group (ECOG) Performance Status Total Score From Baseline

Any TEAE

Any TESAE

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Tachycardia

Supraventricular arrhythmia

Number of Participants With Clinically Significant Changes in Vital Signs From Baseline

Hemoglobin

White blood cells

Absolute neutrophil count

Lymphocytes

Platelets

Activated partial thromboplastin time

Alanine aminotransferase

Aspartate aminotransferase

Alkaline phosphatase

Gamma glutamyl transferase

Albumin

Total bilirubin

Sodium (decrease)

Potassium (increase)

Creatinine

Glucose (increase)

Glucose (decrease)

Calcium (decrease)

Amylase

Lipase

Number of Participants With at Least 2-Grade Change From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

KU-0059436 (AZD2281)(PARP inhibitor)

James Carmichael, BSc MBChB MD FRCP

The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.

Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer

A Phase II Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU 0059436 Given Orally Twice Daily in Patients With Advanced BRCA1 or BRCA2 Associated Ovarian Cancer

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)

The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).

Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.

olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily

Olaparib 100 mg bd

olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily

Olaparib 400 mg bd

BRCA1 or BRCA2 mutations known to cause loss of gene function (clinical deleterious or suspected deleterious mutations).

BRCA mutation

Gerard Lynch

PP Analysis Set

ITT Analysis Set

PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)

Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)

Clinical Benefit (CB)

PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm

Duration of Response

Best Percentage Change in Tumour Size

Progression-Free Survival (PFS)

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

AZD2281

Liposomal Doxorubicin

Jane Robertson, BSc, MBCHB, MD

Stan Kaye, BSc, MB, FRCP, FRCR, SMedSCi

The purpose of the study is to compare the efficacy and safety of 2 doses of drug AZD2281 against liposomal doxorubicin to see which is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and who have failed previous platinum therapy.

Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer

A Phase II, Open-Label, Randomised, Comparative, International Multicentre Study to Assess the Safety and Efficacy of Different Doses of AZD2281 Given Orally Twice Daily Versus Intravenous Liposomal Doxorubicin Given Monthly in Patients With Advanced BRCA1- or BRCA2-Associated Ovarian Cancer Who Have Failed Previous Platinum-based Chemotherapy

PFS was defined as the time to progression from the date of randomisation until the date of radiological assessment of progression per RECIST criteria or death (by any cause in the absence of progression)

ORR was defined according to RECIST. Complete response (CR) or partial response - (PR)- 30% decrease Patients with a best RECIST response of CR or PR had to have a confirmed response at least 28 days later.

The number of patients with confirmed CR (disappearance of all target lesions) or PR (30% decrease in the sum of the longest diameter of target lesions ) or SD ( small changes ) \>4 months, divided by the number of randomised patients

The duration of response was defined as time (months) from initial assessment of PR/CR until earliest date of objective progression or death. (Values may be underestimated as some patients had not progressed at final analysis so true duration is likely to be greater than that in database.)

The percentage change (reduction) from baseline in the sum of the lengths of the longest diameter (LD) of the RECIST target lesions were objectively documented, regardless of whether the patient was still taking study medication

Best percentage change in cancer antigen 125 (CA-125) levels

The percentage of patients reporting a RECIST confirmed response and/or a CA-125 response (in the absence of progression). A CA-125 response was defined as a confirmed greater or equal to 50% reduction in CA-125.

OS was defined as time from randomisation to date of death from any cause. Patients who had not died at time of analysis were censored at last date they were known to be alive. Median OS was not calculable for olaparib groups due to an insufficient number of deaths so the percentage of participants who died are shown along with 95% confidence intervals

Best HRQoL response using the TOI endpoint. Improvement was defined as a change from baseline of greater than or equal to +7. The TOI score ranges from 0-100.

Best HRQoL response using the total FACT-O endpoint. Improvement was defined as a change from baseline of greater than or equal to +9.

Best HRQoL response using the FOSI endpoint. Improvement was defined as a change from baseline of greater than or equal to +3.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer	NCT05485766	Triple Negative... Triple Negative... Breast Neoplasm... Breast Cancer BRCA1 Mutation BRCA2 Mutation BRCA Mutation BRCA-Associated...	Pembrolizumab Paclitaxel Carboplatin Olaparib Definitive Surg...	18 Years -	Okayama University
Evaluation of Tomosynthesis for Characterization and the Management of Breast Lesions	NCT02959398	Breast Neoplasm... Tomosynthesis BRCA1 Protein BRCA2 Protein	Standard mammog... Standard mammog...	18 Years -	Assistance Publique - Hôpitaux de Paris
Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer	NCT00494234	Breast Neoplasm...	Olaparib	18 Years - 130 Years	AstraZeneca
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer	NCT00494442	Ovarian Neoplas...	KU-0059436 (AZD... KU-0059436 (AZD...	18 Years - 130 Years	AstraZeneca
Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer	NCT00628251	Ovarian Neoplas...	AZD2281 Liposomal Doxor... AZD2281	18 Years - 130 Years	AstraZeneca
Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer	NCT00628251	Ovarian Neoplas...	AZD2281 Liposomal Doxor... AZD2281	18 Years - 130 Years	AstraZeneca
A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)	NCT00516373	Ovarian Neoplas... BRCA1 Protein BRCA2 Protein	KU-0059436 (AZD...	18 Years - 130 Years	AstraZeneca
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer	NCT00494442	Ovarian Neoplas...	KU-0059436 (AZD... KU-0059436 (AZD...	18 Years - 130 Years	AstraZeneca

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