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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02285179
Recruitment Status : Suspended (Inclusion stopped due to COVID-19)
First Posted : November 6, 2014
Last Update Posted : January 22, 2021
Genentech, Inc.
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Tracking Information
First Submitted Date  ICMJE October 21, 2014
First Posted Date  ICMJE November 6, 2014
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE November 2014
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
Number of patients with MTD toxicity [ Time Frame: 4 weeks ]
MTD toxicity will be assessed in the first 28 days of treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
  • Safety Number of patients with adverse events [ Time Frame: 2 year ]
    Number of patients with adverse events
  • Pharmacokinetics Number of patients with germline DNA sequence [ Time Frame: 12 months ]
    Number of patients with germline DNA sequence
  • Response Number of patients with a response to protocol treatment [ Time Frame: 2 year ]
    Number of patients with a response to protocol treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen
Official Title  ICMJE Phase I/Prospective Randomized Phase II Trial Of the Safety and Efficacy of Tamoxifen in Combination With GDC-0032 Compared With Tamoxifen alONe.
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.

Detailed Description To determine the recommended phase II dose (RPTD) of GDC-0032 in combination with tamoxifen in hormone receptor positive, HER2 negative metastatic breast cancer patients who have progressed after prior endocrine treatment .Description of toxicity profile, severity and frequency of adverse events (observed with the combination of GDC-0032 and tamoxifen To evaluate the safety and tolerability of GDC-0032 in combination with tamoxifen, recording adverse events using CTCAE v. 4.0 criteria To describe the pharmacokinetics of GDC-0032 in combination with tamoxifen To investigate the possibility of major drug-drug interactions (PK) To obtain proof of target inhibition by selected pharmacodynamic measurements To look for preliminary evidence of anti-tumour activity To assess the status of potential biomarkers for drug response like PIK3CA gene mutations, relevant proteins and phospho-proteins in the PI3K pathway, circulating tumour DNA (ct-DNA) To assess germline DNA sequence for pharmacogenetics studies
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
double blinded study
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: GDC-0032
    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
  • Drug: Tamoxifen
    daily dose of 20 mg
Study Arms  ICMJE
  • Experimental: tamoxifen and GDC-0032
    20 mg tamoxifen QD and 4 MG GDC-0032 QOD
    • Drug: GDC-0032
    • Drug: Tamoxifen
  • Placebo Comparator: tamoxifen and placebo
    20 mg tamoxifen QD and placebo QOD
    Intervention: Drug: Tamoxifen
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: December 7, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2014)
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Netherlands,   Spain,   United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02285179
Other Study ID Numbers  ICMJE M14POS
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Netherlands Cancer Institute
Study Sponsor  ICMJE The Netherlands Cancer Institute
Collaborators  ICMJE
  • Genentech, Inc.
  • EurocanPlatform
  • Rather
Investigators  ICMJE
Principal Investigator: Sabine C. Linn, prof.dr. NKI-AvL
Study Chair: Richard Baird, dr Cambridge University
PRS Account The Netherlands Cancer Institute
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP