E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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 |
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E.1.1.1 | Medical condition in easily understood language |
Patients with advanced cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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
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E.5.1.1 | 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
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E.5.2 | 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 |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |