Clinical Trials /

A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

NCT03337724

Description:

This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2−) breast adenocarcinoma who are not suitable for endocrine therapy.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer
  • Official Title: A Double-Blind, Placebo-Controlled, Randomized Phase III Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Patients With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CO40016
  • SECONDARY ID: 2017-001548-36
  • NCT ID: NCT03337724

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
IpatasertibIpatasertib + Paclitaxel
PaclitaxelIpatasertib + Paclitaxel
PlaceboPlacebo + Paclitaxel

Purpose

This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2−) breast adenocarcinoma who are not suitable for endocrine therapy.

Trial Arms

NameTypeDescriptionInterventions
Ipatasertib + PaclitaxelExperimental
  • Ipatasertib
  • Paclitaxel
Placebo + PaclitaxelExperimental
  • Paclitaxel
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Women or men aged =>18 years with histologically documented triple-negative breast
             cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or
             metastatic and is not amenable to resection with curative intent

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Adequate hematologic and organ function within 14 days prior to treatment initiation

          -  Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
             v1.1

          -  Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or
             freshly cut unstained, serial tumor slides from the most recently collected tumor
             tissue for central molecular analysis:

          -  Valid results from central molecular analysis confirming PIK3CA/AKT1/PTEN-altered
             status in tumor tissue by next-generation sequencing (NGS)

        Exclusion Criteria:

          -  Treatment with approved or investigational cancer therapy within 14 days prior to
             treatment initiation

          -  Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or
             HR+/HER2- adenocarcinoma of the breast

          -  Participants with HR+/HER2- breast cancer for whom endocrine-based therapy is
             considered an appropriate option per local clinical guidelines (i.e. participants
             should not be considered eligible for endocrine-based treatment)

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

          -  Malignancies other than breast cancer within 5 years prior to treatment initiation
             (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin
             carcinoma, or Stage I uterine cancer)

          -  Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)

          -  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 requiring antibiotics

          -  Known human immunodeficiency virus (HIV) infection

          -  Known clinically significant history of liver disease consistent with Child-Pugh Class
             B or C, including active viral or other hepatitis, current drug or alcohol abuse, or
             cirrhosis

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to initiation of treatment (or anticipated need during study)

          -  Pregnant or breastfeeding, or intending to become pregnant during the study

          -  Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart
             failure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmia
             requiring medication, history of myocardial infarction within 6 months of treatment
             initiation, clinically significant electrocardiogram [ECG] abnormalities).

          -  Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or an
             equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a
             chronic disease

          -  Unresolved, clinically significant toxicity from prior therapy

          -  Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, or
             ascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiring
             continued use of bisphosphonate therapy)

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

          -  Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia

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

          -  Clinically significant lung disease (including pneumonitis, interstitial lung disease,
             idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history of
             opportunistic infections)

          -  Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5
             drug-elimination half-lives, whichever is longer, prior to initiation of treatment

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

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 53 months
Safety Issue:
Description:Progression-Free Survival (PFS) as determined by the Investigator using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1)

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 53 months
Safety Issue:
Description:Proportion of participants with an objective response (ORR), defined as partial response or complete response on 2 consecutive occasions ≥4 weeks apart) as determined by the Investigator using RECIST v.1.1
Measure:Duration of Response (DOR)
Time Frame:Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs earlier, up to approximately 53 months
Safety Issue:
Description:Time from the first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause.
Measure:Clinical Benefit Rate (CBR)
Time Frame:From randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, up to approximately 53 months
Safety Issue:
Description:Proportion of participants with a clinical benefit (CB), defined as an objective response (CR or PR), or stable disease for at least 24 weeks, as determined by the Investigator through the use of RECIST v1.1.
Measure:Overall Survival (OS)
Time Frame:From randomization up to death from any cause, up to approximately 53 months
Safety Issue:
Description:Time from randomization to death from any cause.
Measure:Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score
Time Frame:From Day 1 of Cycle 1 up to approximately 53 months
Safety Issue:
Description:GHS/HRQoL scores, assessed using selected questions from European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
Measure:Incidence and Severity of Adverse Events (AEs)
Time Frame:From randomization up to approximately 53 months
Safety Issue:
Description:Percentage of participants with an adverse event (AE), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0, including analysis of pre-specified AEs.
Measure:Changes in Vital Signs
Time Frame:From randomization up to approximately 53 months
Safety Issue:
Description:Change from baseline in selected vital signs.
Measure:Changes in Targeted Laboratory Results
Time Frame:From randomization up to approximately 53 months
Safety Issue:
Description:Change from baseline in selected laboratory test results.
Measure:Plasma Concentration of Ipatasertib and Its Metabolite (G-037720)
Time Frame:Day 1 and Day 15 of Cycle 1, and on Day 15 of Cycle 3
Safety Issue:
Description:

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

November 7, 2017