Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

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

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

300 mg Olaparib (tablets) will be taken orally, twice a day (approximately every twelve hours)

Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase, an enzyme involved in DNA repair.

Olaparib tablet

Kelsey Mitch, RN

Joshua Plassmeyer, MS

Alexander B Olawaiye, MD

This is a prospective non-randomized efficacy trial of olaparib maintenance therapy after frontline treatment with platinum-based therapy in advanced ovarian cancer patients with BRCAwt, homologous recombination deficient (HRD) disease.

The use of PARP inhibitors has revolutionized how we think of the BRCA mutated population of ovarian cancer patients. However, this population with BRCA mutation is not the only one with homologous recombination deficiencies (HRD). Examples of BRCAwt but HR deficient mutations (HRD) include: BRIP1, RAD51C/D, and CHEK2 as well as epigenetic changes like BRCA methylation. This study is designed to provide information on if BRCAwt, HRD patients with advanced ovarian cancer benefit from maintenance olaparib monotherapy after frontline treatment. PAOLA-1 showed that this population had improved PFS from the addition of olaparib to bevacizumab but there is currently no information on how this population does with olaparib alone. For this reason, a similar population to PAOLA-1 will be used in this study. This study is designed to fill an important gap in the data provided by PAOLA-1. It is now considered standard of care for patients with BRCAwt, HRD disease to receive maintenance PARPi either alone (e.g. niraparib) based of PRIMA or in combination with bevacizumab based of PAOLA-1. Therefore, there is little to no concern that patients will be missing out on potentially beneficial therapy that could impact their prognosis.

Upfront Maintenance Olaparib in Advanced Ovarian Cancer BRCAwt Patients With Known Homologous Recombination Deficiency

A Non-randomized Prospective Phase II Study of Upfront Maintenance Olaparib in Advanced Ovarian Cancer BRCAwt Patients With Known Homologous Recombination Deficiency

Time (median number of months) between enrolment and progression (defined by RECIST 1.1) or death, whichever occurs first, and censored at the last date of disease assessment in the absence of progressive disease. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

Percentage of participants free of disease progression at 1 year. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

Time (median number of months) between enrollment and progression or death, whichever occurs first, and censored at the last date of disease assessment in the absence of progressive disease. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

Time (median number of months) between enrollment and second objective disease progression, or death from any cause, whichever occurs first, and censored at last date of disease assessment in the absence of second disease progression. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

Time (median number of months) from enrolment to death from any cause and censored at date of last follow-up.

The EORTC QLQ-C30 is a cancer-specific questionnaire assessing 15 health-related quality of life (HRQoL) scales through 30-items: a global health status, five functional scales (physical, role, emotional, cognitive, and social) and nine symptomatic scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For each dimension, one score is generated on a 0-100 scale, with higher score representing better HRQoL. Minimal clinically important difference defined as ±10 points.

AstraZeneca

Professor, Department of Obstetrics, Gynecology & Reproductive Sciences

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Breast Diseases

Skin Diseases

Adenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Adenocarcinoma of the Appendix

Navitoclax

Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily (bid). Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated. Navitoclax will be administered daily. The initial dose of olaparib 200 mg has been selected after considering the single agent Phase I/II dose based and on ongoing combination studies on expected toxicity and evidence for reduced PARP inhibition

Olaparib tablet will be administered alone for 14 days at a starting dose of 200 mg twice daily. Subsequently olaparib will be administered continuously over 28 days at a fixed dose and the dose of navitoclax will be escalated.

For navitoclax, a lead-in of 7 days at 150 mg PO will be used prior to dose escalation. The DLT period for dose levels above DL 3 will include the 14-day olaparib alone lead-in, the 7 days combination with navitoclax at 150 mg and the first 28 day cycle of the combination of olaparib and navitoclax cycle at the full dose level dosing (49 days).

Helen Mackay

Helen MacKay, MD

Rossanna Pezo, MD

Katarzyna Jerzak, MD

Lilian Gien, MD

Stephanie Lheureux, MD

Neesha Dhani, MD

Gita Bhat, MD

Robert C. Grant, MD

Husam Ali Mahmoud Alqaisi, MD

Amit M. Oza, MD

Diane Provencher, MD

Annick Pina, MD

Beatrice Cormier, MD

Omar Moreira-Basha, MD

Thomas Warkus, MD

Vanessa Samouëlian, MD

The purpose of this Phase I study is to determine if the PARP inhibitor olaparib can be safely combined with navitoclax, an inhibitor of Bcl-2/Bcl-XL, in women with TNBC who have somatic or germline mutations in breast cancer gene one (BRCA1) and breast cancer gene two (BRCA2) BRCA1/2 or PALB2 and in women with recurrent HGSC who have progressed greater than 6 months since their last platinum containing chemotherapy. The trial is designed as an open- label multi-center Phase I interventional and translational study. It will identify the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D of olaparib combined with navitoclax for study in Phase II. There is a plan for a follow on Phase II study depending on the results obtained during this Phase I trial.The rationale for this study is that for a subset of patients, olaparib, will increase tumor cell survival dependence on inhibition of cell death by Bcl 2/Bcl- XL. Thus, navitoclax will augment apoptosis induced by PARP inhibition with olaparib.

In this trial, olaparib will be delivered alone for 14 days with the hypothesis that priming of the apoptotic machinery will be required prior to introduction of the senolytic agent (navitoclax). To date navitoclax and olaparib have not been combined in the clinic. The Phase I study will therefore be conducted to define the recommended Phase II dose (RP2D). A plan for a future Phase II study will depend on the results obtained during this Phase I trial. Based on the potential for overlapping toxicity (particularly hematologic toxicity) an interrupted dosing schedule will be used for the navitoclax. Based on preclinical studies it is believed that intermittent delivery of the senolytic agent is in line with the proposed mechanism of action. Subsequently the dose of navitoclax will be escalated with a fixed dose of olaparib in 28-day cycles.

The trial is designed as an open-label multi-center Phase I interventional and translational study. It will identify the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D of olaparib combined with navitoclax for study in Phase II.

Combination of Olaparib and Navitoclax in Women With HGSC and TNBC

A Phase I Trial of the Combination of Olaparib and Navitoclax in Women With High Grade Serous Epithelial Ovarian Cancer and Triple Negative Breast Cancer

The RP2D will be determined based on an evaluation of multiple endpoints, which will include the DLT( dose limiting toxicity) rate.

The maximum drug concentration will be measured in blood samples as part of the PK profile of olaparib and navitoclax when given in combination.

The time to reach maximum drug concentration will be measured in blood samples as part of the PK profile of olaparib and navitoclax when given in combination.

Exactis Innovation

Centre hospitalier de l'Université de Montréal (CHUM)

Princess Margaret Hospital, Canada

Sunnybrook Health Sciences Centre

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pharmaceutical Solutions

Durvalumab

Antineoplastic Agents, Immunological

Investigator's choice single-agent chemotherapy plus durvalumab 1500 mg every 3 weeks.

Investigator's choice single-agent chemotherapy.

Investigator's choice platinum doublet chemotherapy plus durvalumab 1500 mg every 3 weeks for 4 cycles followed by maintenance durvalumab 1500 mg every 3 weeks plus olaparib 300 mg twice daily.

Investigator's choice platinum doublet chemotherapy plus durvalumab 1500 mg every 3 weeks for 4 cycles followed by maintenance durvalumab 1500 mg every 3 weeks

Durvalumab concentrate for solution for infusion will be supplied in glass vials containing 500 mg durvalumab at a concentration of 50 mg/mL

Olaparib tablets (100 mg and 150 mg strengths) supplied in high-density polyethylene (HDPE) bottles.

Investigator's choice single-agent chemotherapy regimen

Single-agent chemotherapy

Investigator's choice platinum doublet chemotherapy

Platinum doublet chemotherapy

Federico Cappuzzo, MD

Lorenza Landi, MD

This is a randomized, non-comparative, phase II study investigating whether: 1) the addition of durvalumab to investigator's choice second line chemotherapy prolongs survival versus investigator's choice second line chemotherapy in NSCLC patients with locally advanced disease progressing on durvalumab given after concomitant chemoradiotherapy; 2) whether the addition of olaparib to durvalumab improves survival over durvalumab alone after induction chemoimmunotherapy in patients relapsing after completing durvalumab maintenance therapy for stage III disease.

After evaluation of inclusion and exclusion criteria and after consent form signature, all eligible patients progressing during durvalumab therapy will be in the Part A of the trial randomized to in a 1:1 ratio to investigator's choice single-agent chemotherapy plus durvalumab (Arm A: experimental arm) or to investigator's choice single-agent chemotherapy (Arm B: standard arm). In the clinical trial's Part B, patients progressing after completion of durvalumab therapy will be further randomized in a 1:1.7 ratio to investigator's choice platinum doublet chemotherapy plus durvalumab for 4 cycles followed by maintenance durvalumab plus olaparib (Arm C: experimental arm) or to investigator's choice platinum doublet chemotherapy plus durvalumab for 4 cycles followed by durvalumab (Arm D: experimental arm). Therapy will be continued up to disease progression, toxicity or patient refusal.

In the group of individuals progressing during durvalumab theray, patients will be randomized to the experimental arm (durvalumab+chemotherapy) or to the standard arm (chemotherapy alone). The standard arm will act as a calibration arm.

In the second groups patients will be randomized to the experimental arm durvalumab+chemotherapy followed by maintenance durvalumab+olaparib or to the other experimental arm durvalumab+chemotherapy followed by maintenance durvalumab.

Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab

Phase II, Two-cohorts, Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab (MEDI4736)

Overall Survival (OS) rate at 12 months in patients treated in arm A versus B and in patients treated in arm C versus arm D.

Progression free survival (PFS) will be calculated from the date of randomization to the first documented evidence of progressive disease or death due to any cause (whichever occurs first) in patients treated in arm A versus B and in patients treated in arm C versus arm D.

Objective response rate (ORR) is defined as the number of subjects with a best overall response (BOR) of CR or PR divided by the number of randomized subjects for each treatment in each coort.

All adverse events will be reported until 30 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first, and serious adverse events and adverse events of special interest will continue to be reported until 90 days after the final dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurs first.

Progression-free survival (PFS) and Overall survival (OS) will be evaluated according to biomarkers ((i.e., PD-L1, ERCC1, SLFN11, STK11, KEAP1, p53 expression, DNA repair genes \[including BRCA 1-2 mutations\] and tumor mutational burden).

Fondazione Ricerca Traslazionale

Prostatic Neoplasms

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Abiraterone Acetate

Prednisone

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Cytochrome P-450 Enzyme Inhibitors

Subjects will receive a regimen of Olaparib tablets 300 mg twice daily in combination with Abiraterone acetate 1000 mg plus Prednisone 5mg once daily until radiographic disease progression (assessed by the investigator according to RECIST1.1 and PCWG3) or intolerable adverse events (assessed by the investigator according to the actual clinical situation).

Lynparza (Olaparib tablets) 300 mg should be taken orally twice daily.

Qingkeshu (Abiraterone acetate tablets) 1000 mg should be taken orally once daily.

Abiraterone acetate

Prednisone Tablets should be taken 5 mg once daily.

Prednisone tablet

Junlong Zhuang, MD

This is a single-center, single-arm, prospective study to assess the efficacy and safety of Olaparib combined with Abiraterone plus Prednisone in subjects with metastatic hormone sensitive prostate cancer (mHSPC) who carry deleterious germline or homologous recombination repair (HRR) mutations.

Olaparib is an oral, highly selective poly (ADP-ribose) polymerase (PARP) inhibitor that potently inhibits the activity of deoxyribonucleic acid repair polymerases. Abiraterone acetate (AA) is a prodrug of abiraterone that potently inhibits cytochrome P450c17, a key enzyme in androgen biosynthesis.

A total of 30 mHSPC subjects with HRR gene mutations that meet the criteria will be included in the study. Eligible subjects will receive oral Olaparib tablets 300 mg BID, combined with Abiraterone acetate 1000 mg QD plus Prednisone 5 mg, and the study will end when the primary endpoint radiographic progression-free survival (rPFS) data maturity reaches 60%. During the treatment and follow-up periods, all subjects will have regular visits to assess the efficacy and safety of Olaparib in combination with abiraterone acetate plus prednisone. Radiographic progression-free survival (rPFS), prostate-specific antigen response (PSA response rate), prostate-specific antigen progression-free survival (PSA-PFS), radiological objective response rate (ORR) and other indicators will be assessed and calculated.

The Study of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation

A Single-center, Single-arm, Prospective Study to Investigate the Efficacy and Safety of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment

Time from the start of study drug to radiographic progression, or death due to any cause, whichever occurs first.

PSA response is defined as a ≥ 50% decline in PSA from baseline PSA value. This PSA decline must be confirmed as sustained by a second PSA value obtained ≥ 3 weeks later.

PSA-PFS is defined as the time from the start of study drug to the first PSA progression or death due to any cause without progression. PSA progression is defined as a first PSA increase greater than or equal to 25% of baseline and ≥ 2 ng/ml and confirmed a second time after 3 or more weeks.

ORR is the percentage of patients with at least one visit response of Complete response (CR) or Partial response (PR), in their soft tissue disease assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), in the absence of progression on bone scan assessed by Prostate Cancer Working Group 3 (PCWG3)). Per RECIST v1.1, CR=Disappearance of all target lesions; PR = \>=30% decrease in the sum of diameters of target lesions; For each treatment group, ORR is the number of patients with a CR and PR.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Upfront Maintenance Olaparib in Advanced Ovarian Cancer BRCAwt Patients With Known Homologous Recombination Deficiency	NCT06120972	Ovarian Cancer	Olaparib tablet	18 Years -	University of Pittsburgh
Combination of Olaparib and Navitoclax in Women With HGSC and TNBC	NCT05358639	High Grade Sero... Triple Negative... Ovarian Cancer	Olaparib tablet Navitoclax	18 Years -	Sunnybrook Health Sciences Centre
Upfront Maintenance Olaparib in Advanced Ovarian Cancer BRCAwt Patients With Known Homologous Recombination Deficiency	NCT06120972	Ovarian Cancer	Olaparib tablet	18 Years -	University of Pittsburgh
Combination of Olaparib and Navitoclax in Women With HGSC and TNBC	NCT05358639	High Grade Sero... Triple Negative... Ovarian Cancer	Olaparib tablet Navitoclax	18 Years -	Sunnybrook Health Sciences Centre
Randomized Trial Comparing Standard of Care Versus Immune- Based Combination in Relapsed Stage III Non-small-cell Lung Cancer (NSCLC) Pretreated With Chemoradiotherapy and Durvalumab	NCT05568212	Non-small-cell ...	Durvalumab Olaparib tablet Single-agent ch... Platinum double...	18 Years -	Fondazione Ricerca Traslazionale
The Study of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation	NCT05167175	Prostate Cancer Prostate Carcin... Metastatic Pros...	Olaparib tablet Abiraterone ace... Prednisone tabl...	18 Years -	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
The Study of Olaparib Combined With Abiraterone and Prednisone in mHSPC Patients With HRR Gene Mutation	NCT05167175	Prostate Cancer Prostate Carcin... Metastatic Pros...	Olaparib tablet Abiraterone ace... Prednisone tabl...	18 Years -	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Combination of Olaparib and Navitoclax in Women With HGSC and TNBC	NCT05358639	High Grade Sero... Triple Negative... Ovarian Cancer	Olaparib tablet Navitoclax	18 Years -	Sunnybrook Health Sciences Centre

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