Clinical Trials /

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

NCT02301988

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT02301988

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: GO29505
  • SECONDARY ID: 2014-003029-16
  • NCT ID: NCT02301988

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
IpatasertibGDC-0068Ipatasertib + Paclitaxel
PaclitaxelIpatasertib + Paclitaxel
PlaceboPlacebo + Paclitaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Ipatasertib + PaclitaxelExperimentalParticipants 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
Placebo + PaclitaxelPlacebo ComparatorParticipants 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).
  • Paclitaxel
  • Placebo

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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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)
Time Frame:Surgery visit (at approximately Weeks 14 to 19)
Safety Issue:
Description: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.

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Genentech, Inc.

Last Updated

October 17, 2018