Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Immune System Diseases

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Cicatrix

Carcinoma

Fallopian Tube Neoplasms

Peritoneal Neoplasms

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

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Poly(ADP-ribose) Polymerase Inhibitors

Rucaparib

Enzyme Inhibitors

Oral rucaparib

The purpose of this study is to determine which patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib.

Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate \[ADP\] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies. An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutations.

Clinical data with PARP inhibitors indicate there is an ovarian cancer patient population beyond just those with germline BRCA (gBRCA) mutations that may benefit from treatment with a PARP inhibitor. This study will define a molecular signature of HRD in ovarian cancer that correlates with response to rucaparib and enables selection of appropriate ovarian cancer patients for treatment with rucaparib. The HRD signature will be based on an association between the extent of genomic scarring (a downstream consequence of HRD) in a patient's tumor and observed clinical benefit from rucaparib treatment. Genomic scarring can be assessed by quantifying the extent of loss of heterozygosity across the tumor genome (tumor genomic LOH). One of the main advantages of detecting tumor genomic LOH is that it can identify HRD tumors regardless of the underlying mechanisms, which include both known (i.e., BRCA mutations) and unknown genetic and other mechanisms.

Once determined, this signature will be prospectively applied to ARIEL2 PART 2 and ARIEL3. This Phase 2 study (ARIEL2) will also compare archival versus recently collected tumor tissue in order to validate the use of archival tumor tissue for assessment of HRD status in ARIEL3.

This study will include 2 parts:

PART 1 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received ≥1 prior platinum-based regimen and had platinum-sensitive disease

PART 2 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens

A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or PR on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.

Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available.

Foundation Medicine

Myriad Genetics, Inc.

pharmaand GmbH

If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.

All patients who participated in Part 1 who received at least one dose of rucaparib

Part 1 Overall

All patients who participated in Part 2 who received at least one dose of rucaparib

Part 2 Overall

Patients with a deleterious BRCA mutation detected in their tumor.

tBRCA

Patients without a BRCA mutation in their tumor, but have high LOH.

Non-tBRCA LOH+

Patients without a BRCA mutation in their tumor, but have low LOH.

Non-tBRCA LOH-

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).

Non-tBRCA LOH Unknown

Total

Part 1

Part 2

Overall participant count is separated into Part 1 and Part 2 patients.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Number of Prior Chemotherapy Regimens

Number of Prior Platinum Regimens

Refractory = Best response of progressive disease (PD) and PD occurs during or up to 2 months after regimen; Resistant = PD 0-\<6 months after last platinum with best response other than PD; Sensitive = PD ≥6 months after last platinum

Platinum Sensitivity Status

Medical Information Department

Part 1: tBRCA

Part 1: Non-tBRCA LOH+

Part 1: Non-tBRCA LOH-

Part 1: Non-tBRCA LOH Unknown

Safety population by HRD subgroups: Consists of all Part 1 patients who received at least one dose of rucaparib.

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)

Part 2: tBRCA

Part 2: Non-tBRCA LOH+

Part 2: Non-tBRCA LOH-

Part 2: Non-tBRCA LOH Unknown

Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Safety population by HRD subgroups: Consist of all Part 1 patients who received at least one dose of rucaparib

Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)

Safety population by HRD subgroups: Consist of all Part 1 and Part 2 patients who received at least one dose of rucaparib.

Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria

Efficacy population by HRD subgroups. The overall number of patients analyzed includes only patients with confirmed RECIST CR or PR.

Duration of Response Per RECIST v1.1

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)

Overall Survival (Part 2 of Study)

Cycle 1 Day 15

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 1

All Part 1 and Part 2 patients with at least one PK sample collected

Steady State Trough (Cmin) Level Rucaparib Concentrations

Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor. Part 1 enrolled patients who received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.

Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)	NCT01891344	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Peritoneal Canc...	Oral rucaparib	18 Years -	pharmaand GmbH
A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)	NCT01891344	Ovarian Cancer Epithelial Ovar... Fallopian Tube ... Peritoneal Canc...	Oral rucaparib	18 Years -	pharmaand GmbH

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