Clinical trial NCT02301988: A Study of Ipatasertib (GDC-0068) in Combination With Paclitaxel as Neoadjuvant Treatment for Participants With Early Stage Triple Negative Breast Cancer
Official title: A Phase II Randomized, Double-Blind, Study of Ipatasertib (GDC-0068), an Inhibitor to AKT, in Combination With Paclitaxel as Neoadjuvant Treatment for Patients With Early Stage Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: SOLTI Breast Cancer Research Group
First posted: 2014-11-26
Enrollment: 151
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled, multicenter, pre-operative Phase II study designed to estimate the efficacy of ipatasertib combined with paclitaxel chemotherapy versus placebo combined with paclitaxel chemotherapy in women with Stage Ia - IIIa triple-negative breast adenocarcinoma. The anticipated time on study treatment is 12 weeks.


Eligibility criteria: Inclusion Criteria:

* Premenopausal or postmenopausal women
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically documented, Stage Ia to operable Stage IIIa, triple-negative carcinoma of the breast with primary tumor greter than or equal to (\>/=) 1.5 centimeters (cm) in largest diameter (cT1-3) by MRI
* Adequate hematologic and organ function within 14 days before the first study treatment
* Availability of tumor tissue from formalin-fixed, paraffin-embedded (FFPE) core biopsy of breast primary tumor
* For female participants of childbearing potential, agreement to use highly effective form(s) of contraception for the duration of the study and for at least 6 months after last dose of study treatment

Exclusion Criteria:

* Known human epidermal growth factor 2 (HER2)-positive, estrogen receptor (ER)-positive, or progesterone receptor (PgR)-positive breast cancer
* Any prior treatment for the current primary invasive breast cancer
* Participants with cT4 or cN3 stage breast tumors
* Metastatic (Stage IV) breast cancer
* Bilateral invasive breast cancer
* Multicentric breast cancer
* Any disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications

Primary outcomes:
measure: Percentage of Participants With Pathological Complete Response (pCR) in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in All Participants)
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Have Phosphatase and Tensin Homolog [PTEN]-Low Tumors)
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
Secondary outcomes:
measure: Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants)
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Have PTEN-low Tumors)
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With Objective Tumor Response by Magnetic Resonance Imaging (MRI), As Assessed by Investigator Per the Modified Response Evaluation Criteria in Solid Tumors (RECIST) (in All Participants)
timeFrame: Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
measure: Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors)
timeFrame: Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
measure: Percentage of Participants With pCR in Breast and Axilla as Defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Diagnostic Positive [Dx+])
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in Participants Who Are Akt Dx+)
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors
timeFrame: Surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors
timeFrame: From screening to surgery visit (at approximately Weeks 14 to 19)
measure: Percentage of Participants With Adverse Events
timeFrame: Screening up to Week 24
measure: Plasma Concentrations of Ipatasertib on Day 1 and Day 8
timeFrame: 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)
measure: Minimum Observed Plasma Concentration (Cmin) of Ipatasertib
timeFrame: 0.5 and 4 hours post dose on Day 1 of Cycle 1, 166 and 170 hours post dose from Day 1 of Cycle 1 (Cycle length = 28 days)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC-CASA
state: Arizona
city: Santa Barbara
country: United States
facility: Sansum Medical Clinic, Inc.
state: California
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Center - Lakewood (West)
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Danvers
country: United States
facility: Mass General/North Shore Cancer
state: Massachusetts
city: Omaha
country: United States
facility: Nebraska Cancer Specialists; Oncology Hematology West, PC
state: Nebraska
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Portland
country: United States
facility: Northwest Cancer Specialists - Portland (NE Hoyt St)
state: Oregon
city: Charleston
country: United States
facility: Roper Bon Secours St. Francis Cancer Center
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Austin
country: United States
facility: Texas Oncology Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Houston (Gessner)
state: Texas
city: Irving
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: McAllen
country: United States
facility: South Texas Cancer Center - McAllen
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Lisboa
country: Portugal
facility: IPO de Lisboa; Servico de Oncologia Medica
city: Loures
country: Portugal
facility: Hospital Beatriz Angelo; Departamento de Oncologia
city: Porto
country: Portugal
facility: IPO do Porto; Servico de Oncologia Medica
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer; Servicio de Oncologia
state: Islas Baleares
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
state: LA Coruña
city: Lleida
country: Spain
facility: Hospital Universitari de Lleida Arnau de Vilanova
state: Lerida
city: Alcorcón (Madrid)
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Mostoles
country: Spain
facility: Hospital Rey Juan Carlos; Pharmacy
state: Madrid
city: Málaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; hospital Materno Infantil, servicio de Farmacia
state: Malaga
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Sevilla
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus; Servicio de Oncologia
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Caceres
country: Spain
facility: Hospital San Pedro De Alcantara; Servicio de Oncologia
city: Castellon
country: Spain
facility: Hospital Provincial de Castellon; Servicio de Oncologia
city: Girona
country: Spain
facility: Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Oncologico MD Anderson International Espana
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
city: Madrid
country: Spain
facility: Hospital Quiron de Madrid; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario de Fuenlabrada; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario; Oncologia
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Oliveira M, Saura C, Nuciforo P, Calvo I, Andersen J, Passos-Coelho JL, Gil Gil M, Bermejo B, Patt DA, Ciruelos E, de la Pena L, Xu N, Wongchenko M, Shi Z, Singel SM, Isakoff SJ. FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer. Ann Oncol. 2019 Aug 1;30(8):1289-1297. doi: 10.1093/annonc/mdz177.