NCT01968213 · CITED IN SOURCE DOCUMENTS

Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2023-06-09

Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease Progression According to RECIST Version 1.1, as Assessed by the Investigator, or Death From Any Cause (Investigator Progression Free Survival as Per invPFS)

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outcome · POSTED

Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18

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outcome · POSTED

Time to an 8-point Decrease in the Total Score of the FOSI-18

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outcome · POSTED

Individual Model Parameter Estimates of Rucaparib and Covariates Identification

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer. * Received ≥2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial. * Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen. * Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response. * For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response. * Have sufficient archival tumor tissue for analysis. Exclusion Criteria: * History of prior cancer except for non-melanoma skin cancer, breast cancer curatively \> 3 years ago, curatively treated solid tumor (\>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer. * Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible. * Untreated or symptomatic central nervous system metastases. * Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drug. * Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.
healthy Volunteers: false
minimum Age: 18 Years
sex: FEMALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
intervention Names
Drug: Rucaparib
label
Rucaparib
type
EXPERIMENTAL
description
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
intervention Names
Drug: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Rucaparib
description
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
name
Rucaparib
other Names
CO-338
PF 01367338
AG 14699
type
DRUG
arm Group Labels
Placebo
description
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 564
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Progression-free survival by Investigator (invPFS) is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever occurs first. Progressive disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
measure
Disease Progression According to RECIST Version 1.1, as Assessed by the Investigator, or Death From Any Cause (Investigator Progression Free Survival as Per invPFS)
time Frame
Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 3 years.

secondary Outcomes

description
To evaluate PFS by RECIST v1.1, as assessed by independent radiology review (IRR).
measure
Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS)
time Frame
Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 8.2 years.
description
Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive.
measure
Overall Survival (OS)
time Frame
All patients were followed for survival up to approximately 8.2 years.
description
The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related symptoms and is based on numerical point scoring of symptoms. The DRS-P subscale of the questionnaire is specifically designed to assess physical symptoms of ovarian cancer and evaluate changes in the subscale point score in individual assessments over time. This study looked at the time to a 4-point reduction in subscale score as an indicator of improvement in disease-related physical symptoms on cancer therapy.
measure
Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18
time Frame
Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
description
The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related physical, emotional and treatment-related symptoms, and is based on numerical point scoring of symptoms. The questionnaire is designed to evaluate changes in the total score in individual assessments over time. This study looked at the time to an 8-point reduction in the total score as an indicator of improvement in disease-related symptoms on cancer therapy.
measure
Time to an 8-point Decrease in the Total Score of the FOSI-18
time Frame
Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
description
Concentration summary statistics
measure
Individual Model Parameter Estimates of Rucaparib and Covariates Identification
time Frame
Study data collection occurred over approximately 7 months.

Full study description

brief Summary: Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.
detailed Description: 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). Clinical data have shown that ovarian cancer patients with and without evidence of a gBRCA mutation benefit from treatment with a PARP and that maintenance treatment with a PARP inhibitor following a response to platinum-based treatment increases PFS in patients with ovarian cancer. While patients with a BRCA mutation derived the most benefit, patients without evidence of a BRCA mutation also derived significant benefit. Patients enrolled into this study will be stratified into 3 groups based on tumor HRD status. The purpose of this study is to identify which of these groups of patients will most likely benefit from treatment with rucaparib. It is anticipated that rucaparib will provide therapeutic benefit and increase PFS in patients with HRD associated with a BRCA gene mutation or other HR gene alteration.

Source references

references

citation
Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. doi: 10.1016/j.ygyno.2023.05.060. Epub 2023 May 30.
pmid
37262961
type
DERIVED
citation
Green ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
pmid
35397664
type
DERIVED
citation
Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
pmid
35170751
type
DERIVED
citation
Colombo N, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Meunier J, Cameron T, Maloney L, Goble S, Bedel J, Ledermann JA, Coleman RL. The effect of age on efficacy, safety and patient-centered outcomes with rucaparib: A post hoc exploratory analysis of ARIEL3, a phase 3, randomized, maintenance study in patients with recurrent ovarian carcinoma. Gynecol Oncol. 2020 Oct;159(1):101-111. doi: 10.1016/j.ygyno.2020.05.045. Epub 2020 Aug 26.
pmid
32861537
type
DERIVED
citation
Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. doi: 10.1016/S1470-2045(20)30061-9.
pmid
32359490
type
DERIVED
citation
Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12.
pmid
28916367
type
DERIVED