A Study of Ipatasertib (GDC-0068) in Combination With Paclitaxel as Neoadjuvant Treatment for Participants With Early Stage Triple Negative Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02301988
• Other study ID #: GO29505
• Secondary ID: 2014-003029-16
• Status: Completed
• Phase: Phase 2
• Start date: February 17, 2015
• Est. completion date: August 2, 2017

Study information

• Verified date: September 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: August 2, 2017
• Est. primary completion date: August 2, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Ipatasertib
Ipatasertib will be administered at a dose of 400 milligrams (mg) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.
• Paclitaxel
Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m^2) as IV infusion QW for 3 cycles.
• Placebo
Participants will receive placebo (matching to ipatasertib) orally daily on Days 1-21 of each 28-day cycle for 3 cycles.

Locations

Country	Name	City	State
Portugal	IPO de Lisboa; Servico de Oncologia Medica	Lisboa
Portugal	Hospital Beatriz Angelo; Departamento de Oncologia	Loures
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón (Madrid)	Madrid
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	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	Hospital Universitari de Lleida Arnau de Vilanova	Lleida	Lerida
Spain	Centro Integral Oncologico Clara Campal (CIOCC); Dirección Médica	Madrid
Spain	Centro Oncologico MD Anderson International Espana	Madrid
Spain	Fundacion Jimenez Diaz; Servicio de Oncologia	Madrid
Spain	Hospital Quiron de Madrid; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario de Fuenlabrada; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; hospital Materno Infantil, servicio de Farmacia	Málaga	Malaga
Spain	Hospital Rey Juan Carlos; Pharmacy	Mostoles	Madrid
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Islas Baleares
Spain	Hospital Universitari Sant Joan de Reus; Servicio de Oncologia	Reus	Tarragona
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
Spain	Hospital Clinico Universitario; Oncologia	Valencia
United States	Texas Oncology	Austin	Texas
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roper Bon Secours St. Francis Cancer Center	Charleston	South Carolina
United States	Carolinas Healthcare System	Charlotte	North Carolina
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Mass General/North Shore Cancer	Danvers	Massachusetts
United States	Texas Oncology - Houston (Gessner)	Houston	Texas
United States	Texas Oncology-Tyler	Irving	Texas
United States	Rocky Mountain Cancer Center - Lakewood (West)	Lakewood	Colorado
United States	South Texas Cancer Center - McAllen	McAllen	Texas
United States	Nebraska Cancer Specialists; Oncology Hematology West, PC	Omaha	Nebraska
United States	Northwest Cancer Specialists - Portland (NE Hoyt St)	Portland	Oregon
United States	Sansum Medical Clinic, Inc.	Santa Barbara	California
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Arizona Oncology Associates, PC-CASA	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	SOLTI Breast Cancer Research Group

Countries where clinical trial is conducted

United States,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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.	Surgery visit (at approximately Weeks 14 to 19)
Primary	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)	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.	Surgery visit (at approximately Weeks 14 to 19)
Secondary	Percentage of Participants With pCR in Breast as Defined by ypT0/Tis in the American Joint Committee on Cancer Staging System (in All Participants)	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.	Surgery visit (at approximately Weeks 14 to 19)
Secondary	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)	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.	Surgery visit (at approximately Weeks 14 to 19)
Secondary	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)	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.	Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
Secondary	Percentage of Participants With Objective Tumor Response by MRI, As Assessed by Investigator Per Modified RECIST (in Participants Who Have PTEN-low Tumors)	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.	Screening up to disease progression or death (assessed at screening, pre-surgical visit [approximately Weeks 10-12], early termination visit [up to Week 16])
Secondary	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+])	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.	Surgery visit (at approximately Weeks 14 to 19)
Secondary	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+)	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.	Surgery visit (at approximately Weeks 14 to 19)
Secondary	Percentage of Participants With pCR According to American Joint Committee on Cancer Staging System, by Breast Cancer Subtype	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.	Surgery visit (at approximately Weeks 14 to 19)
Secondary	Percentage of Participants With Response to Undergoing Breast Conserving Surgery (BCS) Among Participants With T2 or T3 Tumors	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.	Surgery visit (at approximately Weeks 14 to 19)
Secondary	Percentage of Participants With Response to Conversion to BCS Among Participants With T2 or T3 Tumors	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.	From screening to surgery visit (at approximately Weeks 14 to 19)
Secondary	Percentage of Participants With Adverse Events	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.	Screening up to Week 24
Secondary	Plasma Concentrations of Ipatasertib on Day 1 and Day 8	Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.	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)
Secondary	Minimum Observed Plasma Concentration (Cmin) of Ipatasertib	Plasma samples for pharmacokinetic characterization was collected on Day 1 and Day 8 in all participants.	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)