Randomized trial in postmenopausal women with estrogen receptor-positive, HER2-negative breast cancer in the presurgical setting to test whether the addition of GDC-0032 to letrozole gives added benefit

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2013-000568-28-ES
• Date of registration: 22/05/2014
• Prospective Registration: Yes
• Primary sponsor: Roche Farma S.A en nombre de Genentech, Inc.
• Public title: Randomized trial in postmenopausal women with estrogen receptor-positive, HER2-negative breast cancer in the presurgical setting to test whether the addition of GDC-0032 to letrozole gives added benefit
• Scientific title: A PHASE II RANDOMIZED, DOUBLE-BLIND STUDY OF NEOADJUVANT LETROZOLE PLUS GDC-0032 VERSUS LETROZOLE PLUS PLACEBO IN POSTMENOPAUSAL WOMEN WITH ER-POSITIVE/HER2-NEGATIVE, EARLY STAGE BREAST CANCER
• Date of first enrolment: 30/05/2014
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000568-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Czech Republic, France, Germany, Hungary, Italy, Korea, Republic of, Poland, Portugal, Russian Federation, Spain, Switzerland, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
-Histologically confirmed invasive breast carcinoma, with all of the following characteristics:
- Primary tumor >= 2 cm in largest diameter (cT1-3) by MRI. In the case of a multifocal tumor (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be >= 2 cm and designated as the ?target? lesion for all subsequent tumor evaluations.
- Stage I to operable Stage III breast cancer
- Documentation confirming the absence of distant metastasis (M0) as
determined by institutional practice (in patients where there may be a
reasonable suspicion of advanced disease e.g., large tumors, clinically positive axillary lymph nodes, signs and symptoms).
- ER-positive and HER2-negative breast cancer, as per local laboratory or regional definition
- Breast cancer eligible for primary surgery
- Tumor tissue from FFPE core biopsy of breast primary tumor that is confirmed as evaluable for PIK3CA mutation status by central histopathology laboratory
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Fasting glucose <=125 mg/dL
- Adequate hematological, renal, and hepatic function, as follows:
- Absolute neutrophil count >= 1500/?L
- Platelets count >=100,000/?L
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 198
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 132

Exclusion criteria:
-Any prior treatment for primary invasive breast cancer
-Patients with cT4 or cN3 stage breast tumors
-Metastatic (Stage IV) breast cancer
-Bilateral invasive breast cancer
-Multicentric breast cancer (the presence of more than one tumor in different quadrants of the breast)
-Patients who have undergone excisional biopsy of primary tumor and/or axillary lymph nodes.
- Patients for whom upfront chemotherapy is clinically judged appropriate as optimal neoadjuvant treatment
- Patients for whom immediate surgery is indicated.
-Patients who have undergone sentinel lymph node biopsy prior to study treatment
-Type 1 or 2 diabetes requiring antihyperglycemic medication
-Inability or unwillingness to swallow pills
-Malabsorption syndrome or other condition that would interfere with enteric absorption.
- DLCO <60% of the predicted values (see Appendix 7 for calculations)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

WOMEN WITH ER-POSITIVE/HER2-NEGATIVE, EARLY STAGE BREAST CANCER
MedDRA version: 17.0 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 100000004864

Intervention(s)

Product Name: GDC-0032
Product Code: RO 553-7381/F07
Pharmaceutical Form: Tablet
INN or Proposed INN: taselib
CAS Number: -
Current Sponsor code: GDC-0032
Other descriptive name: RO5537381
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Letrozole
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LETROZOLE
CAS Number: 112809-51-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Primary end point(s): Co-primary endpoints:
1) Tumor ORR, assessed by modified RECIST criteria by breast MRI in all enrolled patients and PIK3CA MT patients
2) Rate of pCR in breast and axilla (total pCR) after completion of study drug in all enrolled patients and PIK3CA MT patients

Timepoint(s) of evaluation of this end point: 1) Tumor ORR evaluated prior to initiating study treatment (baseline) and after completion of study treatment (16 weeks)
2) pCR evaluated after completion of study treatment (16 weeks)

Main Objective: primary objective of this study is to evaluate the efficacy of letrozole plus GDC-0032 versus letrozole plus placebo in women with ER+/HER2- early stage breast cancer, as measured by the following co-primary endpoints:
-Tumor overall objective response rate (ORR) by centrally assessed breast magnetic resonance imaging (MRI) via modified Response Evaluation Criteria in Solid Tumors (RECIST) in all enrolled patients and PIK3CA MT patients
-pCR rate in breast and axilla (ypT0/Tis ypN0) by local evaluation in all enrolled patients and PIK3CA MT patients

Secondary Objective: The secondary efficacy objectives of this study are the following:
-Tumor ORR, assessed by centrally assessed breast MRI via modified Response Evaluation Criteria in Solid Tumors (RECIST) in PIK3CA WT patients
-pCR rate in breast and axilla (total pCR ypT0/Tis ypN0) by local evaluation in PIK3CA WT patients

Secondary Outcome(s)

Secondary end point(s): 1) Tumor ORR after completion of study treatment, assessed by modified RECIST criteria by breast MRI in PIK3CA WT patients
2) Rate of pCR in breast and axilla (total pCR) after completion of study drug in PIK3CA WT patients
The following will be performed in all enrolled patients and separated by PIK3CA mutation status:
3) ORR by clinical breast examination, mammography and breast ultrasound
4) Ki67 values at baseline, Week 3, and surgery
5) Change in Ki67 from baseline to Week 3; baseline to surgery, and Week 3 to surgery
6) PEPI score
7) Change in enhancing tumor volume from baseline to surgery as measured by breast MRI
8) Evaluation of different definitions of pCR including the following: a) ypT0, ypN0, and b) ypT0/is, ypNX (breast pCR).

Timepoint(s) of evaluation of this end point: For secondary endpoints involving ORR and change in enhancing tumor volume, timepoints are prior to initiating study treatment and after completion of study treatment (16 weeks). For pCR and PEPI score, timepoint is completion of study treatment (16 weeks). For Ki67 analyses, timepoints are as listed with surgery occurring within 1 week of completion of the study treatment (16 weeks).

Secondary ID(s)

GO28888

2013-000568-28-BE

Source(s) of Monetary Support

Genentech Inc. c/o F. Hoffmann-La Roche Ltd