The purpose of this research is to see if adding the investigational targeted drug capivasertib to standard endocrine therapy (hormone-blocking treatment) combined with a medicine that slows cancer cell growth can improve response to treatment for patients with metastatic breast cancer that's hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative.
Participants must have histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease.
Participants must have evidence of either 1) measurable disease with or without non-measurable disease, or 2) non-measurable disease only, but the non-measurable disease must include bone metastases. Participants must have a CT scan or MRI of the chest and abdomen AND a whole-body bone scan within 28 days prior to registration. X-rays, scans, or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form.
Participants must have HER2-negative breast cancer, defined as a negative in situ hybridization test or an IHC status of 0 or 1+. If IHC is 2+ (i.e. indeterminate), a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing (as per the ASCO-CAP guidelines).
Participants' most recent tumor biopsy or surgical resection specimen must be either ER-positive, PgR-positive, or both, as defined by immunohistochemistry (IHC) ≥1% (as per the ASCO-CAP guidelines).
Participants must not have active central nervous system (CNS) disease or evidence of active leptomeningeal disease.
Participants must not have had endocrine resistance as defined as breast cancer recurrence within 12 months of cessation of endocrine therapy in the adjuvant setting. Prior adjuvant CDK4/6 inhibitor use is allowed as long as participants did not have a recurrence within 12 months of completion of treatment with an adjuvant CDK4/6 inhibitor.
Participants must not have initiated, but must be planning to initiate, NSAI + palbociclib or ribociclib as the initial therapy for unresectable or metastatic disease.
Participants must not have received prior systemic therapy in the metastatic setting, including chemotherapy or hormone therapy. Prior exposure to any chemotherapy or anti-cancer agents including hormonal therapy in the (neo)adjuvant setting is allowed as long as appropriate washout period before randomization/enrollment is met.
Parallel
NSAI + CDK4/6i
DrugNSAI: Dosed per standard practice, Days 1-28 of every cycle; CDK4/6 Inhibitor (Palbociclib or Ribociclib): Dosed per standard practice, Days 1-21 of every cycle x 4 cycles
NSAI + CDK4/6i + Capivasertib
DrugNSAI: Dosed per standard practice, Days 1-28 of every cycle; CDK4/6 Inhibitor (Palbociclib or Ribociclib): Dosed per standard practice, Days 1-21 of every cycle x 4 cycles; Capivasertib: Dosed 4 days on and 3 days off weekly, every cycle
Fulvestrant + CDK4/6i + Capivasertib
DrugNSAI: Dosed per standard practice, Days 1-28 of every cycle; CDK4/6 Inhibitor (Palbociclib or Ribociclib): Dosed per standard practice, Days 1-21 of every cycle x 4 cycles Capivasertib: Dosed 4 days on and 3 days off weekly, every cycle Fulvestrant: Dosed days 1 and 15 of Cycle 1 and Day 1 of Cycles 2+
NSAI + CDK4/6i
DrugNSAI: Dosed per standard practice, Days 1-28 of every cycle; CDK4/6 Inhibitor (Palbociclib or Ribociclib): Dosed per standard practice, Days 1-21 of every cycle x 4 cycles
Guardant Reveal
Diagnostic testctDNA Assay
PFS
To evaluate progression-free survival (PFS) in participants with HR-positive and HER2 negative unresectable or metastatic breast cancer with detectable circulating tumor DNA (ctDNA) at baseline who do not achieve molecular response but show no evidence of progression per RECIST 1.1 after three cycles of standard of care (SOC) treatment with non-steroidal aromatase inhibitor (NSAI) + CDK4/6 inhibitor in Arms 2 and 3. PFS will be evaluated separately in participants randomized to NSAI + CDK4/6 inhibitor + capivasertib (Arm 2) and fulvestrant + CDK4/6 inhibitor + capivasertib (Arm 3) and compared to historical control.
Molecular Response
All Participants: To assess the percentage of participants who achieve molecular response after cycle 3 of SOC treatment and show stable disease or better per RECIST 1.1.
Cohort A Overall Survival
To evaluate the overall survival (OS) for participants on Arms 1, 2, and 3 (separately).
Cohort A Clinical Benefit Rate
To estimate the clinical benefit rate (CBR) (confirmed or unconfirmed complete or partial response or stable disease ≥ 6 months per RECIST 1.1) separately in Arms 1, 2 and 3 of this participant population from Step 2 Registration.
Cohort A Overall Response Rate
To estimate the overall response rate (ORR) (confirmed complete and partial responses per RECIST 1.1) separately in Arms 1, 2 and 3 of this participant population, among those with measurable disease at Step 2 Registration.
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SWOG Cancer Research Network
Lead sponsor
SWOG Clinical Trials Partnerships, LLC
Collaborator
AstraZeneca
Collaborator
Guardant Health, Inc.
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
