A non-blinded Phase I/II study that evaluates the safety and tolerability of increasing doses of the study drug GDC-0032 administered to patients for the treatment of advanced cancers and in combination with endocrine therapy for the treatment of hormone receptor-positive breast cancer

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2012-002042-21-FR
• Date of registration: 07/01/2015
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public title: A non-blinded Phase I/II study that evaluates the safety and tolerability of increasing doses of the study drug GDC-0032 administered to patients for the treatment of advanced cancers and in combination with endocrine therapy for the treatment of hormone receptor-positive breast cancer
• Scientific title: AN OPEN-LABEL, PHASE I/II, DOSE-ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF GDC-0032 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS AND IN COMBINATION WITH ENDOCRINE THERAPY IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC HORMONE RECEPTOR-POSITIVE BREAST CANCER
• Date of first enrolment: 19/02/2015
• Target sample size: 392
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002042-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Spain, 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:
•Phase I: Histologically documented, locally advanced or metastatic solid malignancy that has progressed or failed to respond to at least one prior regimen and are not candidates for regimens known to provide clinical benefit
• Phase II: Post-menopausal female patients with locally advanced or metastatic HER2-negative, hormone receptor-positive breast cancer
• Evaluable or measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at screening
• Life expectancy of >= 12 weeks
• Adequate haematologic and organ function within 14 days prior to initiation of study treatment
• Documented willingness to use an effective means of contraception for both men and women while participating in the study
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 212
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

Exclusion criteria:
• Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring treatment)
• Grade >=2 peripheral neuropathy
• Active congestive heart failure or ventricular arrhythmia requiring medication
• Patients requiring any daily supplemental oxygen
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Treatment with chemotherapy <= 3 weeks before study treatment
• Treatment with investigational drug <= 4 weeks before study treatment
• Treatment with biologic therapy <= 3 weeks before study treatment
• Treatment with kinase inhibitors <= 2 weeks before study treatment
• Radiation therapy (other than radiation to bony metastases) as cancer therapy <= 4 weeks before study treatment
• Palliative radiation therapy to bony metastases <= 2 weeks before study treatment
• Major surgery <= 4 weeks before study treatment
• Oral endocrine therapy <= 2 weeks prior initiation of study treatment.
• For patients in Phase II and in Stage 2, Cohorts, J, K, L and M: prior treatment with fulvestrant
• For patients in Stage 2, Cohorts, J, K, L, M, N and P and patients in phase II: Prior treatment with > 1 cytotoxic chemotherapy regimen in the metastatic setting. (Prior treatment with everolimus is permitted and is not considered a cytotoxic chemotherapy.)
• Any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or renders the patients at high risk from treatment complications


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with locally advanced or metastatic solid tumors and in combination with endocrine therapy in patients with locally advanced or metastatic hormone receptor-positive breast cancer
MedDRA version: 17.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864

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

Intervention(s)

Trade Name: FASLODEX
Pharmaceutical Form: Solution for injection
INN or Proposed INN: FULVESTRANT
CAS Number: 129453-61-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

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-

Product Name: GDC-0032
Product Code: RO553-7381/F12-01
Pharmaceutical Form: Tablet
INN or Proposed INN: TASELISIB
Current Sponsor code: GDC-0032 (RO5537381)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Main Objective: Phase I
•To evaluate the safety and tolerability of escalating doses of GDC-0032 administered daily to patients with locally advanced or metastatic solid tumors
• To determine the maximum tolerated dose (MTD) of GDC-0032 and to characterize dose-limiting toxicities (DLTs) associated with GDC-0032 when administered daily to patients with locally advanced or metastatic solid tumors
• To characterize the pharmacokinetic (PK) properties of GDC-0032
• To evaluate the safety and tolerability of concomitant administration of GDC 0032 and endocrine therapy in patients with hormone receptorpositive breast cancer

Phase II
• To assess the clinical efficacy of the combination of GDC 0032 and fulvestrant, as measured by the cinical benefit rate and objective response rate, in all patients and patients with PIK3CA mutant breast cancer

Primary end point(s): 1) Incidence of adverse events by NCI CTCAE v4.0 grade and associated dose of GDC-0032
2) Incidence of dose-limiting toxicities (DLTs) by NCI CTCAE v4.0 grade and
associated dose of GDC-0032
3) Incidence of Grade 3 and 4 abnormalities in safety related laboratory parameters and associated dose of GDC-0032
4) Safety in combination with letrozole: incidence of adverse events
5) Safety in combination with fulvestrant: Incidence of adverse events
6) Phase II: Clinical benefit rate with the combination GDC-0032 + fulvestrant
7) Phase II: Objective response rate with the combination GDC-0032 + fulvestrant

Secondary Objective: Phase I
• To make a preliminary assessment of the anti tumor activity of single-agent GDC 0032 in patients with locally advanced or metastatic solid tumors
• To assess the pharmacokinetics of GDC-0032 and endocrine therapy following concomitant administration of GDC-0032 and endocrine therapy

Phase II
• To assess the clinical efficacy of GDC 0032 and fulvestrant, as measured by duration of response, PFS, and OS in all patients and patients with PIK3CA mutant breast cancer
• To determine the nature, severity, and frequency of adverse events associated with the combination of GDC 0032 and fulvestrant
• To evaluate plasma concentrations of GDC 0032 and fulvestrant using a sparse sampling approach.

Timepoint(s) of evaluation of this end point: 1) Up to 3 years
2) Days 1-35
3) Up to 3 years
4) Up to 3 years
5) Up to 4 years
6) Approximately 3 years
7) Approximately 3 years

Secondary Outcome(s)

Secondary end point(s): 1) Best overall response for patients with measurable disease according to RECIST v1.1
2) Duration of objective response for patients with measurable disease according to RECIST v1.1
3) Progression free survival (PFS) for patients with measurable disease according to RECIST v1.1
4) Phase II: Duration of response with the combination GDC-0032 + fulvestrant
5) Phase II: Progression-free survival with the combination GDC-0032 + fulvestrant
6) Phase II: Overall survival with the combination GDC-0032 + fulvestrant

Timepoint(s) of evaluation of this end point: 1) Up to 3 years
2) Up to 3 years
3) Up to 3 years
4) approximately 3 years
5) approximately 3 years
6) approximately 3 years

Secondary ID(s)

NCT01296555

PMT4979g

Source(s) of Monetary Support

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

Ethics review

Status: Approved
Approval date: 19/02/2015
Contact: