A Study of Ipatasertib (GDC-0068) in Combination With Paclitaxel as Neoadjuvant Treatment for Participants With Early Stage Triple Negative Breast Cancer
- Registration Number
- NCT02301988
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 151
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Paclitaxel Placebo Participants will receive placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses). Ipatasertib + Paclitaxel Ipatasertib Participants will receive ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses). Ipatasertib + Paclitaxel Paclitaxel Participants will receive ipatasertib orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel intravenous (IV) infusion every week (QW) for 3 cycles (12 total doses). Placebo + Paclitaxel Paclitaxel Participants will receive placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles and paclitaxel IV infusion QW for 3 cycles (12 total doses).
- Primary Outcome Measures
Name Time Method 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) Surgery visit (at approximately Weeks 14 to 19) pCR was defined by ypT0/Tis ypN0 in the American Joint Committee on Cancer (AJCC) Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
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) Surgery visit (at approximately Weeks 14 to 19) pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants) Surgery visit (at approximately Weeks 14 to 19) pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
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) Surgery visit (at approximately Weeks 14 to 19) pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
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) Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16]) Objective tumor response (OR) was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. OR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors) Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16]) ORR was based on criteria related to changes in size of target lesions according to modified RECIST. Target lesions were selected on the basis of their size (lesions with the longest diameter) as well as the feasibility of reproducible repeated measurements. ORR was the sum of complete response (CR) and partial response (PR). CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
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+]) Surgery visit (at approximately Weeks 14 to 19) pCR was defined by ypT0/Tis ypN0 in the AJCC Staging System with the following determination for breast and axilla by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue and N0: no cancer found in the lymph nodes.
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+) Surgery visit (at approximately Weeks 14 to 19) pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue.
Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype Surgery visit (at approximately Weeks 14 to 19) pCR was defined by ypT0/Tis in the AJCC Staging System with the following determination for breast subtypes by local pathology laboratory evaluation: T0: no evidence of primary tumor; Tis: early cancer that has not spread to neighboring tissue. The intrinsic molecular subtypes of breast cancer included here are luminal A (LumA), Her-2, basal-like, normal and unknown.
Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors Surgery visit (at approximately Weeks 14 to 19) After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors From screening to surgery visit (at approximately Weeks 14 to 19) After neoadjuvant treatment, the number of patients who is appropriate for breast conserving surgery is reported as a measure of efficacy of the treatment to shrink the tumor enough for patients to benefit from less aggressive surgical management. Breast-conserving surgery was defined as removal of part of the breast tissue during surgery. T2 or T3 in the AJCC Staging System were defined as follows: T2: tumor was more than 2 centimeter (cm) but no more than 5 cm across; T3: tumor was larger than 5 cm across.
Percentage of Participants With Adverse Events Screening up to Week 24 An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Plasma Concentrations of Ipatasertib on Day 1 and Day 8 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) Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Minimum Observed Plasma Concentration (Cmin) of Ipatasertib 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) Plasma samples for pharmacokinetic characterization was collected on Day 1 and Day 8 in all participants.
Trial Locations
- Locations (42)
Hospital Universitario Virgen Macarena
🇪🇸Seville, Sevilla, Spain
Arizona Oncology Associates, PC-CASA
🇺🇸Tucson, Arizona, United States
Rocky Mountain Cancer Center - Lakewood (West)
🇺🇸Lakewood, Colorado, United States
Sansum Medical Clinic, Inc.
🇺🇸Santa Barbara, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Mass General/North Shore Cancer
🇺🇸Danvers, Massachusetts, United States
Carolinas Healthcare System
🇺🇸Charlotte, North Carolina, United States
Nebraska Cancer Specialists; Oncology Hematology West, PC
🇺🇸Omaha, Nebraska, United States
Northwest Cancer Specialists - Portland (NE Hoyt St)
🇺🇸Portland, Oregon, United States
Roper Bon Secours St. Francis Cancer Center
🇺🇸Charleston, South Carolina, United States
Texas Oncology Cancer Center
🇺🇸Austin, Texas, United States
Texas Oncology
🇺🇸Austin, Texas, United States
Texas Oncology - Houston (Gessner)
🇺🇸Houston, Texas, United States
South Texas Cancer Center - McAllen
🇺🇸McAllen, Texas, United States
Northwest Medical Specialties, PLLC
🇺🇸Tacoma, Washington, United States
Texas Oncology-Tyler
🇺🇸Irving, Texas, United States
IPO de Lisboa; Servico de Oncologia Medica
🇵🇹Lisboa, Portugal
IPO do Porto; Servico de Oncologia Medica
🇵🇹Porto, Portugal
Hospital Beatriz Angelo; Departamento de Oncologia
🇵🇹Loures, Portugal
Hospital Rey Juan Carlos; Pharmacy
🇪🇸Mostoles, Madrid, Spain
Hospital Universitario Fundación Alcorcón
🇪🇸Alcorcón (Madrid), Madrid, Spain
Hospital Universitari de Lleida Arnau de Vilanova
🇪🇸Lleida, Lerida, Spain
Hospital Regional Universitario Carlos Haya; hospital Materno Infantil, servicio de Farmacia
🇪🇸Málaga, Malaga, Spain
Hospital Universitari Sant Joan de Reus; Servicio de Oncologia
🇪🇸Reus, Tarragona, Spain
Institut Catala d Oncologia Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital San Pedro De Alcantara; Servicio de Oncologia
🇪🇸Caceres, Spain
Hospital Provincial de Castellon; Servicio de Oncologia
🇪🇸Castellon, Spain
Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia
🇪🇸Girona, Spain
Centro Oncologico MD Anderson International Espana
🇪🇸Madrid, Spain
Fundacion Jimenez Diaz; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitario ClÃnico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario de Fuenlabrada; Servicio de Oncologia
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica
🇪🇸Madrid, Spain
Hospital Quiron de Madrid; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clinico Universitario; Oncologia
🇪🇸Valencia, Spain
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
🇪🇸Santiago de Compostela, LA Coruña, Spain
Hospital Son Llatzer; Servicio de Oncologia
🇪🇸Palma de Mallorca, Islas Baleares, Spain
Hospital Universitario Son Espases
🇪🇸Palma De Mallorca, Islas Baleares, Spain