Clinical trial NCT04060862: A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
Official title: A Phase Ib/III Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-08-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The open-label Phase Ib portion of this study will evaluate the safety and pharmacokinetics of ipatasertib in combination with palbociclib and fulvestrant to identify a dose of ipatasertib that can be combined with palbociclib and fulvestrant in the Phase III portion. The randomized Phase III portion of this study will evaluate the efficacy, safety, and patient-reported outcome (PRO) objectives of ipatasertib + palbociclib + fulvestrant compared with placebo + palbociclib + fulvestrant in patients with HR+ HER2-, locally advanced unresectable or metastatic breast cancer who had relapsed during adjuvant endocrine therapy or progressed during the initial 12 months of first-line endocrine therapy in locally advanced unresectable or metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

* HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or metastatic
* For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
* For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm
* Radiologic/objective relapse during adjuvant endocrine therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer
* At least one measurable lesion via Response Evaluation Criteria in Solid Tumors, Version 1.1
* Phase III only: Tumor specimen from the most recently collected, available tumor tissue

Exclusion Criteria:

* Pregnant or breastfeeding, or intending to become pregnant
* Prior treatment with fulvestrant or other selective estrogen receptor down-regulator
* Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor
* Phase III only: Prior treatment with CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer
* Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer
* History of Type I or Type II diabetes mellitus requiring insulin
* History of or active inflammatory bowel disease or active bowel inflammation
* Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections

Primary outcomes:
measure: Phase III: Progression-Free Survival (PFS), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
Secondary outcomes:
measure: Phase Ib: Number of Participants With Adverse Events and Adverse Events With Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
timeFrame: Up to 36 Months
measure: Phase Ib: Plasma Concentration of Ipatasertib and Its Metabolite G-037720
timeFrame: Cycle 1, Day 1 and 15: 0.25 hours pre-dose, 0.5, 1, 2, 3, 4 and 6 hours post- dose ; Cycle 2, Day 15: 0.25 hours pre-dose; Cycle 3, Day 15: 0.15 hours pre-dose, 2 hours post-dose (each cycle = 28 days)
measure: Phase Ib: Maximum Concentration (Cmax) of Ipatasertib and Its Metabolite G-037720 in Plasma
timeFrame: Cycle 1: Day 1 and Day 15
measure: Phase Ib: Area Under the Plasma Concentration Time-curve From Zero to 24 Hours (AUC0-24) of Ipatasertib and Its Metabolite G-037720
timeFrame: Cycle 1: Day 1 and Day 15
measure: Phase Ib: Time to Maximum Concentration (Tmax) of Ipatasertib and Its Metabolite G-037720
timeFrame: Cycle 1: Day 1 and Day 15
measure: Phase III: Objective Response Rate (ORR) as Determined by the Investigator According to RECIST v1.1
timeFrame: From randomization in Phase III up to approximately 36 months
measure: Phase III: Duration of Objective Response (DOR) as Determined by the Investigator According to RECIST v1.1
timeFrame: From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
measure: Phase III: Clinical Benefit Rate (CBR) as Determined by the Investigator According to RECIST v1.1
timeFrame: From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
measure: Phase III: Overall Survival (OS) as Determined by the Investigator According to RECIST v1.1
timeFrame: From randomization in Phase III until the first occurrence of disease progression or death from any cause, whichever occurs first, up to approximately 36 months
measure: Phase III: Time to Deterioration (TTD) in Severity of Pain, According to the Brief Pain Inventory-Short Form (BPI-SF)
timeFrame: From randomization in Phase III to the first documentation of a ≥2-point increase in pain scale (up to approximately 36 months)
measure: Phase III: TTD in Presence and Interference of Pain According to the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) Pain Scale
timeFrame: From randomization in Phase III to the first documentation of a ≥10-point increase (up to approximately 36 months)
measure: Phase III: TTD in Physical Functioning (PF), Role Functioning (RF), GHS/QoL According to EORTC QLQ-C30
timeFrame: From randomization in Phase III to the first documentation of a ≥10-point decrease in the PF, RF and GHS/QoL of EORTC QLQ-C30 (up to approximately 36 months)
measure: Phase III: Number of Participants With Adverse Events
timeFrame: Up to approximately 36 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Piedmont Cancer Institute, PC
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute; GYN Oncology
state: Massachusetts
city: Florham Park
country: United States
facility: Summit Medical Group; MD Anderson Cancer Center
state: New Jersey
city: Malvern
country: Australia
facility: Cabrini Medical Centre; Oncology
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: RS
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre-Calgary
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Clinic; Clinical Trials Department
state: Ontario
city: Quebec City
country: Canada
facility: Hopital du Saint Sacrement
state: Quebec
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia; Servicio de Oncología
city: London
country: United Kingdom
facility: The Royal Marsden Hospital; Dept of Medicine
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit
Study officials:
References: