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History of Changes for Study: NCT04802759
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
Latest version (submitted September 20, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 16, 2021 None (earliest Version on record)
2 April 14, 2021 Arms and Interventions, Study Status, Contacts/Locations, Eligibility and Outcome Measures
3 May 14, 2021 Study Status and Contacts/Locations
4 June 14, 2021 Contacts/Locations and Study Status
5 July 12, 2021 Study Status and Contacts/Locations
6 August 11, 2021 Contacts/Locations and Study Status
7 September 1, 2021 Study Status and Contacts/Locations
8 October 18, 2021 Study Status and Contacts/Locations
9 November 12, 2021 Contacts/Locations, Arms and Interventions, Outcome Measures, Study Status, Eligibility, Study Design and Study Description
10 December 10, 2021 Study Status
11 January 7, 2022 Study Status and Contacts/Locations
12 February 4, 2022 Contacts/Locations and Study Status
13 March 4, 2022 Study Status and Contacts/Locations
14 April 1, 2022 Study Status
15 May 2, 2022 Study Status
16 May 31, 2022 Contacts/Locations and Study Status
17 June 23, 2022 Study Status, Contacts/Locations and Eligibility
18 July 25, 2022 Arms and Interventions, Study Status, Eligibility, Outcome Measures, Study Design and Study Description
19 August 23, 2022 Study Status
20 September 20, 2022 Study Status
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Study NCT04802759
Submitted Date:  March 16, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: CO42867
Brief Title: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
Official Title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Breast Cancer (MORPHEUS- BREAST CANCER)
Secondary IDs: 2020-004889-19 [EudraCT Number]
Open or close this module Study Status
Record Verification: March 2021
Overall Status: Recruiting
Study Start: April 30, 2021
Primary Completion: October 31, 2026 [Anticipated]
Study Completion: April 30, 2027 [Anticipated]
First Submitted: March 15, 2021
First Submitted that
Met QC Criteria:
March 16, 2021
First Posted: March 17, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
March 16, 2021
Last Update Posted: March 17, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary: This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with breast cancer. The current cohort (Cohort 1) will focus on participants with inoperable, locally advanced or metastatic, estrogen receptor (ER)-positive breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; e.g., palbociclib, ribociclib, abemaciclib) in the first- or second-line setting. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the patient population.
Detailed Description:
Open or close this module Conditions
Conditions: Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 6
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 255 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: GDC-9545 Monotherapy Drug: GDC-9545
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Giredestrant
  • RO7197597
  • RG6171
Experimental: GDC-9545 + Abemaciclib Drug: GDC-9545
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Giredestrant
  • RO7197597
  • RG6171
Drug: Abemaciclib
150 mg orally twice a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Verzenio™
Experimental: GDC-9545 + Ipatasertib Drug: GDC-9545
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Giredestrant
  • RO7197597
  • RG6171
Drug: Ipatasertib
400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-0068
  • RO5532961
  • RG7440
Experimental: GDC-9545 + GDC-0077 Drug: GDC-9545
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Giredestrant
  • RO7197597
  • RG6171
Drug: GDC-0077
9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Inavolisib
  • RO7113755
  • RG6114
Experimental: GDC-9545 + Ribociclib Drug: GDC-9545
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Giredestrant
  • RO7197597
  • RG6171
Drug: Ribociclib
600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Kisqali®
Experimental: GDC-9545 + Everolimus Drug: GDC-9545
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Giredestrant
  • RO7197597
  • RG6171
Drug: Everolimus
10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • Afinitor®
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percentage of Participants with Objective Response, Defined as a Complete or Partial Response, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
[ Time Frame: From Baseline until disease progression (up to 6 years) ]

2. Number of Participants with Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)
[ Time Frame: From Baseline until 30 days after the last dose of study drug (up to 6 years) ]

3. Plasma Concentration of GDC-9545 at Specified Timepoints
[ Time Frame: Day 1 of Cycles 1, 2, 4, 8, and 16 (each cycle is 28 days), and at treatment discontinuation visit (within 30 days after last dose) ]

4. Plasma Concentration of Abemaciclib at Specified Timepoints
[ Time Frame: Days 1 and 15 of Cycle 1; Day 1 of Cycles 2 and 3 (each cycle is 28 days), and at treatment discontinuation visit (within 30 days after last dose) ]

5. Plasma Concentration of Ipatasertib at Specified Timepoints
[ Time Frame: Days 1 and 15 of Cycle 1; Day 1 of Cycles 2 and 3 (each cycle is 28 days) ]

6. Plasma Concentration of GDC-0077 at Specified Timepoints
[ Time Frame: Days 1 and 15 of Cycle 1; Day 1 of Cycles 2 and 3 (each cycle is 28 days) ]

7. Plasma Concentration of Ribociclib at Specified Timepoints
[ Time Frame: Days 1 and 15 of Cycle 1; Day 1 of Cycle 2 (each cycle is 28 days) ]

8. Blood Concentration of Everolimus at Specified Timepoints
[ Time Frame: Days 1 and 15 of Cycle 1; Day 1 of Cycle 2 (each cycle is 28 days) ]

Secondary Outcome Measures:
1. Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1
[ Time Frame: From randomization to the date of the first recorded occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years) ]

2. Disease Control Rate, Defined as the Percentage of Participants with Stable Disease for ≥12 Weeks or a Complete or Partial Response, as Determined by the Investigator According to RECIST v1.1
[ Time Frame: From Baseline until disease progression (up to 6 years) ]

3. Clinical Benefit Rate, Defined as the Percentage of Participants with Stable Disease for ≥24 Weeks or with Confirmed Complete or Partial Response, as Determined by the Investigator According to RECIST v1.1
[ Time Frame: From Baseline until disease progression (up to 6 years) ]

4. Overall Survival
[ Time Frame: From randomization to death from any cause (up to 6 years) ]

5. Duration of Response, as Determined by the Investigator According to RECIST v1.1
[ Time Frame: From first occurrence of a document objective response to the first date of recorded disease progression or death from any cause, whichever occurs first (up to 6 years) ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Female
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

Inclusion Criteria for Cohort 1:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Documented estrogen receptor-positive (ER+) tumor
  • Patients for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
  • Radiologic/objective evidence of recurrence or progression after the most recent systemic therapy for breast cancer
  • Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease (note: at least one line of therapy must have contained a CDK4/6i administered for a minimum of 8 weeks prior to disease progression.)
  • Postmenopausal status for women
  • Life expectancy ≥3 months
  • Availability of a representative tumor specimen that is suitable for evaluation of Ki67, and/or additional biomarkers via central testing
  • Prior fulvestrant therapy is allowed
  • Measurable disease
  • Adequate hematologic and end-organ function
  • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

Exclusion Criteria:

General Exclusion Criteria for Cohort 1:

  • Known HER2-positive breast cancer
  • Prior treatment with cytotoxic chemotherapy for metastatic breast cancer
  • Concurrent hormone replacement therapy
  • Prior treatment with any of the protocol-specified study treatments
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Systemic treatment for ER+ breast cancer within 2 weeks of Cycle 1, Day 1 or 5 half-lives of the drug prior to Cycle 1, Day 1
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤1 or better, with the exception of alopecia of any grade and Grade ≤2 peripheral neuropathy
  • Prior allogeneic stem cell or solid organ transplantation
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
  • History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
  • Uncontrolled tumor-related pain
  • Uncontrolled or symptomatic hypercalcemia
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • History of leptomeningeal disease
  • Active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
  • Active cardiac disease or history of cardiac dysfunction
  • Positive HIV test at screening or at any time prior to screening
  • Active Hepatitis B or Hepatitis C virus infection
  • Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery, including gastric resection, potentially affecting enteral absorption
  • Known allergy or hypersensitivity to any of the study drugs or any of their excipients

GDC-9545 + Ipatasertib Arm Exclusion Criteria:

  • Prior treatment with an Akt inhibitor
  • Grade ≥2 uncontrolled or untreated hypercholesterolemia or hypertriglyceremia
  • History of Type 1 or Type 2 diabetes mellitus requiring insulin
  • Congenital long QT syndrome or screening QTcF >480 milliseconds
  • History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion
  • Treatment with strong CYP3A4 inducers and inhibitors within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug

GDC-9545 + Abemaciclib Arm Exclusion Criteria:

  • Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
  • History of major surgical resection involving the stomach or small bowel, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea
  • History of syncope of cardiovascular etiology, ventricular arrhythmia, or sudden cardiac arrest

GDC-9545 + GDC-0077 Arm Exclusion Criteria:

  • Prior treatment with any PI3K, Akt, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K/Akt/mTOR pathway
  • Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
  • Fasting glucose ≥126 mg/dL or ≥7.0 mmol/L and HbA1c ≥5.7%
  • Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition
  • Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
  • Symptomatic active lung disease, including pneumonitis
  • Inability to confirm biomarker eligibility based on valid results from either central testing of blood or local testing of blood or tumor tissue that documents one of the protocol-defined PIK3CA mutations

GDC-9545 + Ribociclib Arm Exclusion Criteria:

  • Currently receiving any of the following substances within 7 days before randomization: concomitant medications, herbal supplements, and/or fruits that are known as strong inhibitors or inducers of CYP3A4/5 or medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  • Currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting trial treatment
  • Impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: CO42867 www.roche.com/about_roche/roche_worldwide.htm
Telephone: 888-662-6728 (U.S. Only)
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: United States, California
City of Hope
[Not yet recruiting]
Duarte, California, United States, 91010
University of California, San Francisco (UCSF)
[Not yet recruiting]
San Francisco, California, United States, 94143
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
[Not yet recruiting]
Santa Monica, California, United States, 90404
Stanford Cancer Institute (SCI)
[Not yet recruiting]
Stanford, California, United States, 94305
United States, Massachusetts
Massachusetts General Hospital
[Not yet recruiting]
Boston, Massachusetts, United States, 02114
United States, Minnesota
University of Minnesota Medical Center (UMMC)
[Not yet recruiting]
Minneapolis, Minnesota, United States, 55455
United States, North Carolina
Levine Cancer Institute
[Not yet recruiting]
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
Thomas Jefferson University Hospital;Medical Oncology
[Not yet recruiting]
Philadelphia, Pennsylvania, United States, 19107
University of Pittsburgh Cancer Institute
[Not yet recruiting]
Pittsburgh, Pennsylvania, United States, 15219
Australia, South Australia
Flinders Medical Centre
[Not yet recruiting]
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Peninsula Private Hospital
[Not yet recruiting]
Frankston, Victoria, Australia, 3199
Australia, Western Australia
Linear Clinical Research Limited
[Not yet recruiting]
Nedlands, Western Australia, Australia, 6009
Israel
Hadassah Ein Karem Hospital
[Recruiting]
Jerusalem, Israel
Rabin MC; Davidof Center - Oncology Institute
[Not yet recruiting]
Petach Tikva, Israel, 4941492
The Chaim Sheba Medical Center
[Not yet recruiting]
Ramat Gan, Israel, 5211401
Tel Aviv Sourasky Medical Center; Movement Disorder
[Not yet recruiting]
Tel Aviv, Israel, 6423906
Korea, Republic of
National Cancer Center
[Not yet recruiting]
Goyang-si, Korea, Republic of, 10408
Seoul National University Hospital
[Not yet recruiting]
Seoul, Korea, Republic of, 03080
Spain
Hospital Universitario Vall d'Hebron
[Not yet recruiting]
Barcelona, Spain, 08035
Hospital Universitario Ramón y Cajal
[Not yet recruiting]
Madrid, Spain, 28034
Centro Integral Oncológico Clara Campal Ensayos Clínicos START
[Not yet recruiting]
Madrid, Spain, 28050
Hospital Clinico Universitario de Valencia; Servicio de Anatomia Patologica
[Not yet recruiting]
Valencia, Spain, 46010
Open or close this module IPDSharing
Plan to Share IPD: No

Qualified researchers may request access to individual patient level data through the 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 Sharing of Clinical Study 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).

Open or close this module References
Citations:
Links:
Available IPD/Information:

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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services