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Ovarian CancerPhase 2ARIEL2NCT01891344

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

A Phase 2 study testing Oral rucaparib in people with Ovarian Cancer and Epithelial Ovarian Cancer, run by pharmaand GmbH at 75 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Oral rucaparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
491 participants
Where
75 sitesin 6 countries
Study dates
30 Oct 2013to 28 Sep 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have a histologically confirmed diagnosis of high grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
  • Received at least 3 prior chemotherapy regimens. Non-chemotherapy regimens and maintenance therapies administered as single agent treatment will not count as a chemotherapy regimen
  • Relapsed/progressive disease as confirmed by CT scan
  • Have biopsiable and measurable disease. Note: biopsy is optional for patients known to harbor a deleterious gBRCA mutation
  • Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses

Who cannot join

  • History of prior cancers except for those that have been curatively treated, with no evidence of cancer currently (provided all chemotherapy was completed >6 months prior and/or bone marrow transplant >2 years prior to first dose of rucaparib).
  • Prior treatment with any PARP inhibitor
  • Symptomatic and/or untreated central nervous system metastases
  • Pre-existing duodenal stent and/or any other gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
  • Hospitalization for bowel obstruction within 3 months prior to enrollment

Trial locations and contacts

75 sites in 6 countries.

75 sites in 6 countries

United States36 sites

  • Women's Cancer Care Associates

    Albany, New York, 12208

  • Providence Alaska Medical Center

    Anchorage, Alaska, 99508

  • Hope - A Woman's Cancer Institute

    Asheville, North Carolina, 28006

  • Johns Hopkins Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Cincinnati Physicians Company

    Cincinnati, Ohio, 45206

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Saint Jude Heritage Medical Center

    Fullerton, California, 92835

  • Comprehensive Cancer Centers of Nevada

    Henderson, Nevada, 89014

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • Horizon BioAdvance

    Lafayette, Indiana, 47905

  • Altus Research

    Lake Worth, Florida, 33461

  • Rocky Mountain Cancer Centers

    Lakewood, Colorado, 80228

  • University of California Los Angeles

    Los Angeles, California, 90404

  • Norton Cancer Institute

    Louisville, Kentucky, 40241

  • University of Miami Hospital & Clinics Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • New York University Langone Medical Center

    New York, New York, 10016

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma

    Oklahoma City, Oklahoma, 73019

  • Florida Hospital Cancer Institute

    Orlando, Florida, 32804

  • UF Health Cancer Center

    Orlando, Florida, 32806

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • UPMC Cancer Center

    Pittsburgh, Pennsylvania, 15213

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • UC San Diego

    San Diego, California, 92093

  • California Pacific Medical Center

    San Francisco, California, 94115

  • University of California, San Francisco

    San Francisco, California, 94158

  • Coastal Integrative Cancer Care

    San Luis Obispo, California, 93401

  • Central Coast Medical Oncology

    Santa Maria, California, 93454

  • University of Washington - Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

  • University of Arizona Cancer Center

    Tucson, Arizona, 85719

Other trials in United States

Canada11 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N4N2

  • Cross Cancer Centre

    Edmonton, Alberta, T6G1Z2

  • British Columbia Cancer Agency

    Kelowna, British Columbia, V1Y 5L3

  • London Regional Cancer Centre

    London, Ontario, N6A4L6

  • Centre Hospitalier de L'Universite de Montreal

    Montreal, Quebec, H2L 4M1

  • Jewish General Hospital

    Montreal, Quebec, H3T 1E2

  • Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H8L6

  • CHU de Québec - Université Laval

    Québec, G1R 2J6

  • BC Cancer Agency - Fraser Valley Centre

    Surrey, British Columbia, V3V 1Z2

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G2M9

  • Vancouver Cancer Centre, British Columbia Cancer Agency (BCCA)

    Vancouver, British Columbia, V5Z4E6

Other trials in Canada

United Kingdom9 sites

  • Addenbrooke's Hospital

    Cambridge, CB20QQ

  • Beatson West of Scotland Cancer Centre

    Glasgow, Scotland, G120YN

  • St James University Hospital

    Leeds, West Yorkshire, LS97TF

  • Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • Imperial College Healthcare NHS Trust - Hammersmith Hospital

    London, W120HS

  • University College London

    London, W1T4TJ

  • The Christie NHS Foundation Trust

    Manchester, M204BX

  • Sir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care

    Newcastle upon Tyne, NE77DN

  • Royal Marsden Sutton Hospital

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Australia8 sites

  • Flinders Cancer Clinic - Flinders Medical Centre (FMC)

    Bedford Park, South Australia, 5042

  • Mercy Hospital for Women

    Heidelberg, Victoria, 3084

  • Royal Brisbane & Women's Hospital

    Herston, Queensland, 4029

  • Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Royal Melbourne Hospital

    Parkville, Victoria, 3052

  • Royal North Shore Hospital

    Saint Leonards, New South Wales, 2065

  • Prince of Wales Hospital

    Sydney, New South Wales, 2031

  • Crown Princess Mary Cancer Centre (Westmead Hospital)

    Westmead, Wentworthville, NSW 2145

Other trials in Australia

France8 sites

  • Institut Bergonie

    Bordeaux, Aquitaine, 33076

  • Centre Leon Berard

    Lyon, Auvergne-Rhône-Alpes, 69373

  • Centre Catherine de Sienne

    Nantes, Pays de la Loire Region, 44202

  • Hopital Tenon

    Paris, Île-de-France Region, 75020

  • Hôpital Européen Georges-Pompidou

    Paris, Île-de-France Region, 75908

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, Auvergne-Rhône-Alpes, 69495

  • Institut Claudius Regaud

    Toulouse, Midi-Pyrenees, 31052

  • Institut de cancerologie Gustave Roussy

    Villejuif, Île-de-France Region, 94805

Other trials in France

Spain3 sites

  • Hospital Vall d'Hebron

    Barcelona, 8035

  • Instituto Valencia de Oncologia

    Valencia, 46009

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

About this study

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

Read the 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). 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

Being tested
Oral rucaparib
Keywords
ovarian cancer, fallopian tube cancer, primary peritoneal cancer, peritoneal cancer, platinum sensitive, relapsed disease, PARP Inhibitor, rucaparib, homologous recombination, homologous recombination deficiency, genomic scarring, loss of heterozygosity, CO-338, PF 01367338, AG 14699, platinum sensitive ovarian cancer, platinum sensitive fallopian tube cancer, platinum sensitive primary peritoneal cancer, platinum sensitive peritoneal cancer, gynecological cancer
Medical subject headings
Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral rucaparibDrug

    Also called CO-338, PF 01367338, AG 14699

    600 mg BID

Study groups in NCT01891344
Study groupRoleWhat they receive
Ovarian cancerExperimentalrucaparib
Receives: Drug: Oral rucaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

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

    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.

    Measured: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Secondary outcomes (6)

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

    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.

    Measured: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

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

    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.

    Measured: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

  3. Duration of Response Per RECIST v1.1

    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.

    Measured: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

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

    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.

    Measured: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

  5. Overall Survival (Part 2 of Study)

    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.

    Measured: All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.

  6. Steady State Trough (Cmin) Level Rucaparib Concentrations

    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.

    Measured: Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2013 (estimated)
  2. Study start30 Oct 2013
  3. Primary completion5 Nov 2019
  4. Study completion28 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
491 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01891344
Sponsor's protocol ID
CO-338-017
Other IDs
2013-000517-20
Acronym
ARIEL2
Status last verified
Jun 2023
First submitted
20 Jun 2013
Last updated
12 Jun 2023
Data monitoring committee
No

Publications

  • 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.

    PubMed 35397664

  • 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.

    PubMed 35170751

  • Swisher EM, Kwan TT, Oza AM, Tinker AV, Ray-Coquard I, Oaknin A, Coleman RL, Aghajanian C, Konecny GE, O'Malley DM, Leary A, Provencher D, Welch S, Chen LM, Wahner Hendrickson AE, Ma L, Ghatage P, Kristeleit RS, Dorigo O, Musafer A, Kaufmann SH, Elvin JA, Lin DI, Chambers SK, Dominy E, Vo LT, Goble S, Maloney L, Giordano H, Harding T, Dobrovic A, Scott CL, Lin KK, McNeish IA. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2). Nat Commun. 2021 May 3;12(1):2487. doi: 10.1038/s41467-021-22582-6.

    PubMed 33941784

  • Kristeleit RS, Oaknin A, Ray-Coquard I, Leary A, Balmana J, Drew Y, Oza AM, Shapira-Frommer R, Domchek SM, Cameron T, Maloney L, Goble S, Lorusso D, Ledermann JA, McNeish IA. Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety. Int J Gynecol Cancer. 2019 Nov;29(9):1396-1404. doi: 10.1136/ijgc-2019-000623.

    PubMed 31685558

  • Swisher EM, Lin KK, Oza AM, Scott CL, Giordano H, Sun J, Konecny GE, Coleman RL, Tinker AV, O'Malley DM, Kristeleit RS, Ma L, Bell-McGuinn KM, Brenton JD, Cragun JM, Oaknin A, Ray-Coquard I, Harrell MI, Mann E, Kaufmann SH, Floquet A, Leary A, Harding TC, Goble S, Maloney L, Isaacson J, Allen AR, Rolfe L, Yelensky R, Raponi M, McNeish IA. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017 Jan;18(1):75-87. doi: 10.1016/S1470-2045(16)30559-9. Epub 2016 Nov 29.

    PubMed 27908594

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oral rucaparib in people with Ovarian Cancer and Epithelial Ovarian Cancer, run by pharmaand GmbH at 75 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 75 sites in United States, Canada, United Kingdom, Australia, France and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study) (time frame: Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01891344, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.

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