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A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer

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ClinicalTrials.gov Identifier: NCT04802759
Recruitment Status : Recruiting
First Posted : March 17, 2021
Last Update Posted : June 16, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer Drug: Giredestrant Drug: Abemaciclib Drug: Ipatasertib Drug: Inavolisib Drug: Ribociclib Drug: Everolimus Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 255 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : June 30, 2021
Estimated Primary Completion Date : October 31, 2026
Estimated Study Completion Date : April 30, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Active Comparator: Giredestrant Monotherapy Drug: Giredestrant
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-9545
  • RO7197597
  • RG6171

Experimental: Giredestrant + Abemaciclib Drug: Giredestrant
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-9545
  • RO7197597
  • RG6171

Drug: Abemaciclib
150 mg orally twice a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Name: Verzenio™

Experimental: Giredestrant + Ipatasertib Drug: Giredestrant
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-9545
  • 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: Giredestrant + Inavolisib Drug: Giredestrant
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-9545
  • RO7197597
  • RG6171

Drug: Inavolisib
9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-0077
  • RO7113755
  • RG6114

Experimental: Giredestrant + Ribociclib Drug: Giredestrant
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-9545
  • 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 Name: Kisqali®

Experimental: Giredestrant + Everolimus Drug: Giredestrant
30 milligrams (mg) orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Names:
  • GDC-9545
  • RO7197597
  • RG6171

Drug: Everolimus
10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
Other Name: Afinitor®




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 Giredestrant 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 Inavolisib 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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
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

Giredestrant + 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

Giredestrant + 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

Giredestrant + Inavolisib 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

Giredestrant + 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04802759


Contacts
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Contact: Reference Study ID Number: CO42867 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
Show Show 26 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04802759    
Other Study ID Numbers: CO42867
2020-004889-19 ( EudraCT Number )
First Posted: March 17, 2021    Key Record Dates
Last Update Posted: June 16, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

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).


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Everolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs