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OVARIAN CANCERPhase 1NCT03695380

A Clinical Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab to Patients With Advanced Platinum-sensitive Ovarian Cancer

A Phase 1 study testing Cobimetinib, Niraparib and Atezolizumab in people with OVARIAN CANCER, run by Hoffmann-La Roche at 20 sites in 3 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 study will include a safety run-in phase (Stage 1) and a randomization phase (Stage 2). The purpose of Stage 1 is to evaluate the safety of cobimetinib when administered in combination with niraparib (Cohort 1) and cobimetinib with niraparib plus atezolizumab (Cohort 2). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
OVARIAN CANCER
What is being tested?
Cobimetinib, Niraparib and Atezolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
20 sitesin 3 countries
Study dates
9 Jan 2019to 12 Jul 2023
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Ability to comply with the study protocol, in the investigator's judgment
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of patient-reported outcome questionnaires
  • Histological diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
  • Previous treatment with a minimum of one and a maximum of two prior platinum based treatment regimens
  • Platinum-sensitive disease
  • Availability of tumor biopsy tissue prior to first dose of study treatment with confirmation by the central laboratory that the sample is not only of adequate quality but also assignable to a molecularly defined subgroup based on breast cancer susceptibility gene (BRCA) and loss of heterozygosity (LOH) status
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  • Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
  • Adequate hematologic and organ function
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Life expectancy of at least 12 weeks
  • Resolved or stabilized toxicities resulting from previous therapy to Grade 1
  • Negative HIV test at screening
  • Negative hepatitis B surface antigen and total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA < 500 IU/mL test at screening
  • Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test at screening
  • For women of childbearing potential: Women must remain abstinent or use two contraceptive methods with a failure rate of <1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib, 6 months after the last dose of niraparib, and 5 months after the last dose of atezolizumab. Women must refrain from donating eggs during this same period

Who cannot join

  • Prior treatment with mitogen-activated protein kinase inhibitor, polyadenosine diphosphate-ribose polymerase inhibitor, or immune checkpoint inhibitor therapies
  • Prior chemotherapy, hormonal therapy, radiotherapy, antibody therapy, or other immunotherapy, gene therapy, vaccine therapy, or treatment with experimental drugs within 14 days prior to first dose of study treatment
  • Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medication 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the study
  • History of other malignancy that could affect compliance with the protocol or interpretation of results, or known to have potentially fatal outcome
  • Symptomatic and/or untreated central nervous system metastases
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  • Surgical procedure, significant traumatic injury within 14 days prior to enrollment, or anticipation of need for major surgical procedure during the study
  • Minor surgical procedure within 3 days
  • History or evidence of retinal pathology on ophthalmic examination
  • Left ventricular ejection fraction below institutional lower limit of normal
  • History of clinically significant cardiovascular dysfunction
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan
  • History or evidence of inherited bleeding diathesis or significant coagulopathy at risk for bleeding
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or to any component of the atezolizumab formulation
  • Known allergy or hypersensitivity to any component of the cobimetinib or niraparib formulation
  • Active or history of autoimmune disease or immune deficiency including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barre syndrome, or multiple sclerosis
  • Uncontrolled serious medical or psychiatric illness
  • History of malabsorption or other condition that would interfere with absorption of oral study drugs, including preexisting duodenal stent or ongoing intestinal obstruction
  • Active tuberculosis
  • Severe infection within 14 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Treatment with therapeutic oral or IV antibiotics within 7 days prior to initiation of study treatment
  • Treatment with a live, attenuated influenza vaccine within 28 days prior to study treatment initiation, at any time during the study, and for at least 5 months after the last dose of study drug
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
  • Previous treatment with strong CYP3A inhibitors (such as ketoconazole and clarithromycin), strong CYP3A inducers (such as carbamazepine and phenytoin), and moderate CYP3A inducers (such as efavirenz, modafinil) within 7 days prior to the initiation of study treatment or with ongoing requirements for these medications
  • Pregnancy or breastfeeding, or intention to become pregnant during the study

Trial locations and contacts

20 sites in 3 countries.

20 sites in 3 countries

United States9 sites

  • Medical College of Georgia; Obstetrics & Gynecolog

    Augusta, Georgia, 30912-3335

  • Mayo Clinic-Jacksonville

    Jacksonville, Florida, 32224

  • Moores Cancer Center at UC San Diego Health

    La Jolla, California, 92093

  • Medical College of Wisconsin; Department of Obstetrics and Gynecology

    Milwaukee, Wisconsin, 53226

  • Tennessee Oncology; Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Stephenson Cancer Center Investigational Pharmacy

    Oklahoma City, Oklahoma, 73104

  • Florida Hospital Cancer Institute; Clinical Research Department

    Orlando, Florida, 32804

  • Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology

    St Louis, Missouri, 63108

  • University of Arizona Cancer Center, North

    Tucson, Arizona, 85719

Other trials in United States

Spain8 sites

  • Centro Oncologico de Galicia COG; Medical Oncology

    A Coruña, LA Coruña, 15009

  • Hospital Universitari Vall dHebron; Oncology

    Barcelona, 08035

  • ICO Girona

    Girona, 17007

  • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia

    Jaén, 23007

  • Clinica Universidad de Navarra Madrid; Servicio de Oncología

    Madrid, 28027

  • Hospital Ramon y Cajal; Servicio de Oncologia

    Madrid, 28034

  • Hospital Clinico San Carlos; Servicio de Oncologia

    Madrid, 28040

  • Hospital Clínico Universitario de Valencia; Servicio de Oncología

    Valencia, 46010

Other trials in Spain

Italy3 sites

  • Istituto Europeo di Oncologia; Svil. Nuovi Farmaci per Terapie Innovative

    Milan, Lombardy, 20141

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples, Campania, 80131

  • Fondazione Policlinico Universitario "A. Gemelli"; Unità di Fase 1: Unità di Farmacologia Clinica

    Rome, Lazio, 00168

Other trials in Italy

About this study

Official title: A Phase Ib Study of Cobimetinib Administered in Combination With Niraparib, With or Without Atezolizumab, To Patients With Advanced Platinum-sensitive Ovarian Cancer

The study will include a safety run-in phase (Stage 1) and a randomization phase (Stage 2).

The purpose of Stage 1 is to evaluate the safety of cobimetinib when administered in combination with niraparib (Cohort 1) and cobimetinib with niraparib plus atezolizumab (Cohort 2).

Read more

Stage 1 will enable patient enrollment in the randomized phase of the study (Stage 2) with both regimens at the recommended dose levels from Stage 1.

Stage 2 is a randomized, dose-expansion phase, evaluating clinical outcomes in patients with advanced platinum-sensitive ovarian cancer.

All patients will continue to receive study treatment until disease progression (according to "Response Evaluation Criteria in Solid Tumors" (RECIST), Version 1.1, unacceptable toxicity, death, or patient or investigator decision to withdraw, whichever occurs first.

Conditions
OVARIAN CANCER
Being tested
Cobimetinib, Niraparib, Atezolizumab
Medical subject headings
Ovarian Neoplasms

What participants receive

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

  • CobimetinibDrug

    Cobimetinib will be administered at a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle (Stage 1) and PO QD on Days 1-21 (21/7 schedule) at the established dose for the doublet regimen in Stage 1 (Stage 2).

  • NiraparibDrug

    Niraparib will be administered at a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle (Stage 1) and PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1 (Stage 2).

  • AtezolizumabDrug

    Atezolizumab will be administered by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle (Stages 1 and 2).

Study groups in NCT03695380
Study groupRoleWhat they receive
Arm A: Cobimetinib - NiraparibExperimentalStage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1, Cohort 1.
Receives: Drug: Cobimetinib; Drug: Niraparib
Arm B: Cobimetinib - Niraparib - AtezolizumabExperimentalStage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.
Receives: Drug: Cobimetinib; Drug: Niraparib; Drug: Atezolizumab
Cohort 1 - Cobimetinib - NiraparibExperimentalStage 1 - Patients in Cohort 1 will be treated with cobimetinib plus niraparib. Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle. Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle.
Receives: Drug: Cobimetinib
Cohort 2 - Cobimetinib - Niraparib - AtezolizumabExperimentalStage 1 - Patients in Cohort 2 will be treated with cobimetinib plus niraparib and atezolizumab. Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle. Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle. Atezolizumab: Patients will also receive atezolizumab administered as an IV infusion at a fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle.
Receives: Drug: Cobimetinib

What is being measured

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

  1. Number of patients reporting Adverse Events (AEs)

    The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of number of patients reporting serious and non-serious AEs with severity graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI - CTCAE v5.0)

    Measured: From baseline up to 48 months

  2. Change from baseline in targeted clinical laboratory test results

    The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumabwill be evaluated in terms of number of patients reporting change from baseline in targeted clinical laboratory test results.

    Measured: From baseline up to 48 months

  3. Investigator-assessed confirmed objective response rate (ORR)

    The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of investigator-assessed confirmed ORR, as determined using RECIST v1.1 in the Intention To Treat (ITT) population and in molecularly defined subgroups by loss of heterozygosity (LOH) status.

    Measured: From baseline up to 48 months

Secondary outcomes (6)

  1. Progression-free survival (PFS)

    The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first, in the ITT population and in the molecularly defined subgroups by LOH status.

    Measured: From Baseline up to 48 months

  2. Duration of response (DOR)

    The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of DOR, defined for patients achieving at least one confirmed Partial Response (PR), which is measured from the first observation of a Complete Response (CR) or a PR to the time of disease progression in the ITT population and in the molecularly defined subgroups by LOH status.

    Measured: From baseline up to 48 months

  3. Overall survival (OS)

    The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of OS after randomization, defined as the time from randomization until death from any cause in the ITT population and in the molecularly defined subgroups by LOH status.

    Measured: From baseline up to 48 months

  4. Plasma concentration of cobimetinib and niraparib

    The Pharmacokinetic (PK) profile of cobimetinib plus niraparib is evaluated in terms of Plasma concentration at specified timepoints.

    Measured: Arm A: Day 15 of Cycle 1 and 2 - Arm B: Day 15 of Cycle 1

  5. Serum concentration of atezolizumab

    The PK profile of cobimetinib plus niraparib plus atezolizumab will be evaluated in terms of Serum concentration of atezolizumab at specified timepoints (Arm B only).

    Measured: Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months

  6. Number of patients with Anti-Drug Antibodies (ADA)

    The immunogenicity profile of Atezolizumab is evaluated in terms of number of patients with ADA at baseline and during the study.

    Measured: Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months

Timeline

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

  1. First posted4 Oct 2018
  2. Study start9 Jan 2019
  3. Primary completion12 Jul 2023
  4. Study completion12 Jul 2023

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03695380
Sponsor's protocol ID
YO40482
Other IDs
2018-000631-27, 2018
Status last verified
Aug 2023
First submitted
30 Sep 2018
Last updated
14 Aug 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Publications

  • Mutch D, Voulgari A, Chen XM, Bradley WH, Oaknin A, Perez Fidalgo JA, Montosa FG, Herraez AC, Holloway RW, Powell MA, Nowicka M, Schaefer G, Merchant M, Yan Y. Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti-PD-L1, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer. Cancer. 2024 Jun 1;130(11):1940-1951. doi: 10.1002/cncr.35222. Epub 2024 Jan 30.

    PubMed 38288862

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cobimetinib, Niraparib and Atezolizumab in people with OVARIAN CANCER, run by Hoffmann-La Roche at 20 sites in 3 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 15 inclusion and 25 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 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, Spain, Italy. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of patients reporting Adverse Events (AEs) (time frame: From baseline up to 48 months). The study lists 3 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 NCT03695380, which also lists 1 linked publication.

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 14 Aug 2023.

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