Breast Cancer
Conditions
Brief summary
The purpose of this study is to find out whether a new drug, Ipatasertib, can slow the growth of advanced breast cancer when added to standard therapy (Fulvestrant).
Detailed description
Patients enrolled in this study will receive either Ipatasertib plus Fulvestrant or placebo (a substance that looks like the study drug but does not have any active or medicinal ingredient) plus Fulvestant. The study will provide information about the ability of Ipatasertib plus Fulvestrant to control the cancer, the side effects and safety of the treatment, how patients feel while taking the treatment and associated costs.
Interventions
DRUGIpatasertib
400 mg PO QD days 1-21 every 28 days
DRUGFulvestrant
500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles
OTHERPlacebo
PO QD days 1-21 every 28 days
Sponsors
Canadian Cancer Trials Group
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer * Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study * Clinical and/or radiographic progression during treatment with or within 28 days after discontinuation of first line of treatment with a CDK 4/6 inhibitor and an aromatase inhibitor (AI) for advanced/metastatic disease * Evidence of clinically and/or radiologically documented disease * ≥ 18 years of age * ECOG performance status of 0 or 1 * No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy * Must not have received more than one prior line of treatment with a CDK 4/6 inhibitor and an AI in the advanced disease setting. * Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study * Adequate hematology and organ function, in the absence of growth factors * Absolute neutrophils \> 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Hemoglobin \> 90 g/L * Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome * ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis) * Alkaline phosphatase ≤ 2.0 x ULN (or ≤ 5.0 x ULN if liver metastases, ≤ 7.0 x ULN if bone metastasis) * Fasting glucose ≤ 8.3 mmol/L * HbA1c ≤ 7.5% * Serum albumin ≥ 30 g/L * INR ≤ 1.2 * Serum Creatinine or Creatinine clearance ≤ 1.5 x ULN or ≥ 50 mL/min; measured directly by 24-hour urine sampling or as calculated by Crockcroft and Gault equation
Exclusion criteria
* Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days * Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption * Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors * Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome * Active or uncontrolled infections or serious illnesses or medical conditions * Clinically significant liver diseases * History of lung disease or history of opportunistic infections * Type 1 or Type 2 diabetes mellitus requiring insulin * Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia * Known abnormalities in coagulation * History of hypersensitivity to the study drugs or components * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression-free Survival (PFS) Using RECIST 1.1 | 4 years | Progression-free survival (PFS) defined as time from randomization to disease progression or death from any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Compare the Two Treatment Arms With Respect to Investigator Assessed PFS (Per RECIST 1.1) in the PIK3CA/AKT1/PTEN Altered Cohort | 4 years | The PFS is tested in the PIK3CA/PTEN/AKT1 altered status subset under the same 0.05 significance level among the 111 subjects in the PIK3CA/PTEN/AKT1 altered status subset |
| Commencement of Subsequent Line of Systemic Therapy or Death (TSST) | 4 years | Number of patients with commencement of subsequent line of systemic therapy or death between enrollment and the end of study |
Countries
Australia, Canada, New Zealand
Contacts
STUDY_CHAIRStephen Chia
BCCA - Vancouver Cancer Centre, BC Canada
Participant flow
Recruitment details
Dates of the recruitment period: January 27, 2021 to May 08, 2024
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60 Years |
| Body Mass Index | 27.72 Kg per meter square (kg/(m*m)) STANDARD_DEVIATION 5.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 107 Participants |
| Region of Enrollment Australia | 29 Participants |
| Region of Enrollment Canada | 180 Participants |
| Region of Enrollment New Zealand | 12 Participants |
| Sex: Female, Male Female | 247 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 42 / 125 | 36 / 125 |
| other Total, other adverse events | 124 / 124 | 120 / 124 |
| serious Total, serious adverse events | 18 / 124 | 18 / 124 |
Outcome results
None listed