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

• Register: ClinicalTrials.gov
• Last refreshed on: 20 February 2023
• Main ID: NCT03337724
• Date of registration: 07/11/2017
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public 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 IPATunity130
• Scientific 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
• Date of first enrolment: January 6, 2018
• Target sample size: 580
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03337724
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Costa Rica, Czechia, France, Germany, Greece, Hungary, India, Italy, Japan, Korea, Republic of, Macedonia, The Former Yugoslav Republic of, Mexico, North Macedonia, Peru, Poland, Russian Federation, Singapore, Slovenia, South Africa, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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

- Histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that is
locally advanced or metastatic and is not amenable to resection with curative intent

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

- Eligible for taxane monotherapy, as per local investigator assessment (e.g., absence
of rapid clinical progression, life-threatening visceral metastases, or the need for
rapid symptom and/or disease control which may require combination chemotherapy)

- HR+/HER2- breast cancer that is not considered appropriate for endocrine-based therapy
and meets one of the following: patient has recurrent disease <=5 years of being on
adjuvant endocrine therapy or if patient with de novo metastatic disease have
progressed within 6 months of being on first line endocrine therapy.

- 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

- Confirmation of biomarker eligibility using an appropriately validated molecular assay
at a diagnostic laboratory, Clinically Laboratory Improvement Amendments (CLIA) or
equivalently accredited i.e., valid results from either central testing or local
testing of tumor tissue or blood demonstrating PIK3CA/AKT1/PTEN-altered status

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception and agreement to refrain from donating
eggs

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive methods and agreement to refrain from donating sperm

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 (patients receiving neo/adjuvant chemotherapy
eligible provided they have at least a 12 month disease-free interval)

- 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 systemic anti-microbial treatment (including antibiotics,
anti-fungals, and anti-viral agents)

- 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, except for alopecia
and Grade 1 peripheral neuropathy

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Placebo

Drug: Ipatasertib

Drug: Paclitaxel

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score [Time Frame: From Day 1 of Cycle 1 up to approximately 53 months]

Incidence and Severity of Adverse Events (AEs) [Time Frame: From randomization up to approximately 53 months]

Overall Survival (OS) [Time Frame: From randomization up to death from any cause, up to approximately 53 months]

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]

Changes in Targeted Laboratory Results [Time Frame: From randomization up to approximately 53 months]

Changes in Vital Signs [Time Frame: From randomization up to approximately 53 months]

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]

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]

Time to Deterioration in Pain [Time Frame: From Day 1 of Cycle 1 up to approximately 53 months]

Secondary ID(s)

CO40016

2017-001548-36

Source(s) of Monetary Support

Please refer to primary and secondary sponsors