- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02285179
Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen (Poseidon)
Phase I/Prospective Randomized Phase II Trial Of the Safety and Efficacy of Tamoxifen in Combination With GDC-0032 Compared With Tamoxifen alONe.
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.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Paris, France
- Gustave Roussy
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Amsterdam, Netherlands, 1066 CX
- Antoni van Leeuwenhoek
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Delft, Netherlands
- Reinier de Graaf Gasthuis
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Den Haag, Netherlands
- Haaglanden Medisch Centrum
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Deventer, Netherlands
- Deventer Ziekenhuis
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Hengelo, Netherlands
- Ziekenhuis Groep Twente
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Maastricht, Netherlands
- MUMC
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Badalona, Spain
- Hospital Germans Trias i Pujol
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Barcelona, Spain
- Hospital Clinic de Barcelona
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Barcelona, Spain, 080035
- Vall d'Hebron University Hospital/VHIO
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Barcelona, Spain
- Hospital ICO-Hospitalet (Bellvitge)
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Lleida, Spain
- Hospital Arnau de Vilanova
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Tarragona, Spain
- Hospital Universitari Sant Joan de Reus
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Cambridge, United Kingdom, CB20QQ
- University of Cambridge
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria:
Minimum age for inclusion 18 years
- 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.
exclusion criteria:
- 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
- Other malignancy with the exclusion of carcinoma in situ.
- 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).
- The patient has a previously identified allergy or hypersensitivity to components of the study treatment formulation(s).
- The patients is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
- Pregnant or nursing women
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: tamoxifen and GDC-0032
20 mg tamoxifen QD and 4 MG GDC-0032 QOD
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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
daily dose of 20 mg
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Placebo Comparator: tamoxifen and placebo
20 mg tamoxifen QD and placebo QOD
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daily dose of 20 mg
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of patients with MTD toxicity
Time Frame: 4 weeks
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MTD toxicity will be assessed in the first 28 days of treatment
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4 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Safety Number of patients with adverse events
Time Frame: 2 year
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Number of patients with adverse events
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2 year
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Pharmacokinetics Number of patients with germline DNA sequence
Time Frame: 12 months
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Number of patients with germline DNA sequence
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12 months
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Response Number of patients with a response to protocol treatment
Time Frame: 2 year
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Number of patients with a response to protocol treatment
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2 year
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sabine C. Linn, prof.dr., NKI-AVL
- Study Chair: Richard Baird, dr, Cambridge University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- M14POS
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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