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A Study to Evaluate the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer

NCT03800836

Description:

This is a Phase Ib, open-label, multicenter study evaluating the safety and efficacy of ipatasertib in combination with atezolizumab and paclitaxel or nab-paclitaxel for patients with locally advanced or metastatic triple-negative breast cancer (mTNBC) who have not previously received chemotherapy in the advanced setting. Two triplets; ipatasertib in combination with atezolizumab and paclitaxel (Paclitaxel arm) and ipatasertib in combination with atezolizumab and nab-paclitaxel (Nab-Paclitaxel arm) are being evaluated for first-line chemotherapy treatment for advanced TNBC. Cohort 1 will evaluate first-line chemotherapy treatment in advanced TNBC patients and Cohort 2 will contain biopsy assessments of TNBC patients who have progressed after at least one line of chemotherapy in the advanced setting.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer
  • Official Title: A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Patients With Locally Advanced or Metastatic Triple-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CO40151
  • NCT ID: NCT03800836

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
IpatasertibPaclitaxel Arm: Ipatasertib + Atezolizumab + Paclitaxel
PaclitaxelPaclitaxel Arm: Ipatasertib + Atezolizumab + Paclitaxel
AtezolizumabPaclitaxel Arm: Ipatasertib + Atezolizumab + Paclitaxel
Nab-PaclitaxelNab-Paclitaxel Arm: Ipatasertib+Atezolizumab+Nab-Paclitaxel

Purpose

This is a Phase Ib, open-label, multicenter study evaluating the safety and efficacy of ipatasertib in combination with atezolizumab and paclitaxel or nab-paclitaxel for patients with locally advanced or metastatic triple-negative breast cancer (mTNBC) who have not previously received chemotherapy in the advanced setting. Two triplets; ipatasertib in combination with atezolizumab and paclitaxel (Paclitaxel arm) and ipatasertib in combination with atezolizumab and nab-paclitaxel (Nab-Paclitaxel arm) are being evaluated for first-line chemotherapy treatment for advanced TNBC. Cohort 1 will evaluate first-line chemotherapy treatment in advanced TNBC patients and Cohort 2 will contain biopsy assessments of TNBC patients who have progressed after at least one line of chemotherapy in the advanced setting.

Trial Arms

NameTypeDescriptionInterventions
Paclitaxel Arm: Ipatasertib + Atezolizumab + PaclitaxelExperimentalParticipants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by intravenous (IV) infusion on Days 1 and 15 of each 28 day cycle. Paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All patients in this study will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
  • Ipatasertib
  • Paclitaxel
  • Atezolizumab
Nab-Paclitaxel Arm: Ipatasertib+Atezolizumab+Nab-PaclitaxelExperimentalParticipants will receive ipatasertib orally daily on Days 1-21 of each 28 day cycle, and atezolizumab will be administered by IV infusion on Days 1 and 15 of each 28 day cycle. Nab-paclitaxel will be administered by IV infusion on Days 1, 8, and 15 of each 28 day cycle. All patients in this study will continue to be treated until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.
  • Ipatasertib
  • Atezolizumab
  • Nab-Paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group Performance Status of 0 or 1

          -  Adequate hematologic and organ function

          -  Life expectancy of at least 6 months

          -  For men and women of child bearing potential: agreement to remain abstinent or use
             protocol defined contraceptive measures during the treatment period and for at least
             28 days after the last dose of ipatasertib, 6 months after the last dose of
             paclitaxel, and 5 months after the last dose of atezolizumab, whichever occurs later

          -  Histologically documented TNBC that is locally advanced or metastatic

          -  Measurable disease according to RECIST v1.1

        Exclusion Criteria:

          -  History of malabsorption syndrome or other condition that would interfere with enteral
             absorption or results in the inability or unwillingness to swallow pills

          -  Active infection

          -  History of or current evidence of HIV infection

          -  Known clinically significant history of liver disease

          -  Pregnant or breastfeeding

          -  Left ventricular ejection fraction < 50%

          -  Prior treatment with an Akt inhibitor

          -  History of or known presence of brain or spinal cord metastases

          -  Patients may have received prior neoadjuvant or adjuvant chemotherapy and/or radiation
             treatment for early stage breast cancer, provided all chemotherapy was completed >= 12
             months prior to Day 1 of Cycle 1

          -  Uncontrolled tumor related complications

          -  Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1

          -  History of Type I or Type II diabetes mellitus requiring insulin

          -  Uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia

          -  History of or active inflammatory bowel disease or active bowel inflammation

          -  Clinically significant lung disease

          -  Treatment with strong CYP3A inhibitors or strong CYP3A inducers

          -  Active or history of autoimmune disease or immune deficiency

          -  Prior allogeneic stem cell or solid organ transplantation

          -  History of hypersensitivity reactions to study drug or any component of the study drug
             formulation

          -  Treatment with systemic immunostimulatory agents and immunosuppressive medication
             treatment, or anticipation of need for systemic immunosuppressive medication during
             the course of the study

          -  Grade >= 2 peripheral neuropathy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Cohort 1: Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR]), as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST), Version (v) 1.1
Time Frame:Baseline up to disease progression or treatment discontinuation, whichever occurs first (to approximately 12 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Cohort 1: Progression-Free Survival, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Safety Issue:
Description:
Measure:Cohort 1: Percentage of Participants who have an Objective Response (Complete or Partial), or Stable Disease for at least 24 weeks, as Assessed by Investigator Based on RECIST v1.1
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Safety Issue:
Description:
Measure:Cohort 1: Overall Survival in All Participants
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Safety Issue:
Description:
Measure:Cohort 1: Plasma Concentration of Ipatasertib
Time Frame:At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Safety Issue:
Description:
Measure:Cohort 1: Plasma Concentration of Ipatasertib's Metabolite (G-037720)
Time Frame:At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Safety Issue:
Description:
Measure:Cohort 1: Presence of Anti-Drug Antibody During Study Treatment
Time Frame:At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Safety Issue:
Description:
Measure:Cohort 1: Plasma Concentration of Atezolizumab
Time Frame:At Day 1 and Day 15 of Cycles 1-3, and Day 1 of Cycle 4 (each cycle is 28 days)
Safety Issue:
Description:
Measure:Cohort 1 and Cohort 2: Percentage of Participants with Adverse Events
Time Frame:Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 12 months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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