Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen

NCT02285179 | Completed Phase 1 DMC

• 1 other identifier: M14POS
• Study Type: interventional
• Target: 189
• Locations: 4 countries
• Sites: 14

Brief Summary

This study is designed as a phase 1 dose escalation study followed by a randomised phase II study. The study will be performed in three different centres: Addenbrooke \& Cambridge university (Cambridge, UK), Netherlands Cancer Institute Amsterdam), and Vall d'Hebron Hospital (Barcelona, Spain). Three to six patients will be followed for one completed cycle of therapy (28 days) and subsequent enrolment of new cohorts will be based on the safety assessment in that first cycle and the documentation of dose limiting toxicities. To determine the safety and efficacy of tamoxifen in combination with the isoform selective Pi3K inhibitor GDC-0032 compared with tamoxifen alone.

Conditions

Breast Cancer

Keywords

GDC-0032; Pi3K inhibitor; tamoxifen; hormone receptor positive; RECIST; pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• Number of patients with MTD toxicity

  MTD toxicity will be assessed in the first 28 days of treatment

  4 weeks

Secondary Outcomes (3)

• Safety Number of patients with adverse events

  2 year

• Pharmacokinetics Number of patients with germline DNA sequence

  12 months

• Response Number of patients with a response to protocol treatment

  2 year

Study Arms (2)

tamoxifen and GDC-0032

EXPERIMENTAL

20 mg tamoxifen QD and 4 MG GDC-0032 QOD

Drug: GDC-0032; Drug: Tamoxifen

tamoxifen and placebo

PLACEBO COMPARATOR

20 mg tamoxifen QD and placebo QOD

Drug: Tamoxifen

Interventions

GDC-0032 DRUG

Dose of GDC-0032 given orally, once daily (total daily dose) level -1: 2 mg Q.O.D GDC-0032 level 1: (starting) 2 mg QD for 21 days, 7 days off and tamoxifen 20 mg qd level 2: 4 mg QD for 21 days, 7 days off and tamoxifen 20 mg qd

tamoxifen and GDC-0032

Tamoxifen DRUG

daily dose of 20 mg

tamoxifen and GDC-0032; tamoxifen and placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has a WHO performance status ≤ 2
• Premenopausal and postmenopausal female breast cancer patient with histological proven ER and/or PR positive\*, HER2 negative breast cancer (based on the most recent assessment of ER and PR status from primary breast cancer or from recurrent or metastatic disease). If a patient is premenopausal by clinical and analytical assessment (defined as having premenopausal follicle stimulating hormone (FSH) and/or plasma estradiol levels), she should also receive a LHRH agonist.
• The patient's breast cancer must be negative for HER2 over-expression by IHC (IHC score ≤1+) or for HER2 gene amplification by FISH or CISH or SISH
• Patients must have either measurable or evaluable disease by RECIST criteria version 1.1.
• The patient has recurrent or metastatic breast cancer that is refractory to an endocrine therapy defined as the occurrence of either of the following while the patient is on endocrine therapy:
• Disease progression of locally advanced or metastatic breast cancer
• Disease recurrence of early stage breast cancer (i.e., recurrence while receiving adjuvant treatment with endocrine therapy)
• Availability of a representative tumour tissue specimen:
• If a patient is currently receiving bisphosphonates, the patient must have received the bisphosphonates for at least 1 month before starting study treatment.
• The patient has adequate organ and marrow function, as defined in protocol.
• The patient has no other diagnosis of malignancy or evidence of other malignancy for 2 years before screening for this study (except non-melanoma skin cancer or in situ carcinoma of the cervix).
• Life expectancy ≥ 12 weeks.
• Fasting glucose ≤ 120 mg/dL (=6.66 mmol/L) and HbA1c ≤ ULN.

You may not qualify if:

• The following restrictions on prior anticancer therapy apply;
• Endocrine therapies or small molecule targeted (non-cytotoxic) inhibitors within 2 weeks or 5 half-lives of the compound or active metabolites, whichever is longer, before the first dose of the study treatment are not allowed
• No more than 5 prior chemotherapeutic regimens for metastatic breast cancer
• Radiation therapy within 2 weeks before the first dose of study treatment, unless of palliative intent, not compromising bone marrow function
• Cytotoxic chemotherapy within 3 weeks, or nitrosoureas or mitomycin C within 6 weeks before the first dose of the study treatment
• Antibody therapy within 4 weeks before the first dose of the study treatment
• Major surgery or not recovered from major surgery, within 4 weeks before the first dose of study treatment
• The patient has not recovered from toxicity due to prior therapy to grade ≤1 or to pre-therapy baseline. Patients with grade 2 peripheral neuropathy or grade 2 alopecia related to prior therapies are eligible
• The patient has untreated, symptomatic, or progressive brain metastases. -The patient has a history of thrombo-embolic disease or is currently receiving anticoagulation with therapeutic doses of warfarin.
• The patient has prothrombin time/ International Normalized Ratio (PT/ INR) or partial thromboplastin time (PTT) test results at screening that are above 1.3 x the laboratory upper limit of normal.
• Patients with a history of Crohn's disease or ulcerative colitis or other forms of autoimmune colitis
• The patient has uncontrolled significant intercurrent illness
• History of clinically significant cardiac or pulmonary dysfunction-The patient has a type 1 or 2 diabetes requiring daily anti-hyperglycemic medication
• Corticosteroid use equivalent to more than 10mg prednisone daily
• The patient is known to be positive for the human immunodeficiency virus (HIV).

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Genentech, Inc.: collaborator
• EurocanPlatform: collaborator
• Rather: collaborator

Study Sites (14)

Gustave Roussy

Paris, France

Location

Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, Netherlands

Location

Deventer Ziekenhuis

Deventer, Netherlands

Location

Ziekenhuis Groep Twente

Hengelo, Netherlands

Location

MUMC

Maastricht, Netherlands

Location

Haaglanden Medisch Centrum

The Hague, Netherlands

Location

Hospital Germans Trias i Pujol

Badalona, Spain

Location

Vall d'Hebron University Hospital/VHIO

Barcelona, 080035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital ICO-Hospitalet (Bellvitge)

Barcelona, Spain

Location

Hospital Arnau de Vilanova

Lleida, Spain

Location

Hospital Universitari Sant Joan de Reus

Tarragona, Spain

Location

University of Cambridge

Cambridge, CB20QQ, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

2-(3-(2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo(f)imidazo(1,2-d)(1,4)oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Sabine C. Linn, prof.dr.

  NKI-AvL

  PRINCIPAL INVESTIGATOR

• Richard Baird, dr

  Cambridge University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double blinded study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: November 6, 2014
• Study Start: November 1, 2014
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: October 12, 2022

Record last verified: 2022-10

Locations

ES (6); FR (1); NL (6); GB (1)