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

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ClinicalTrials.gov Identifier: NCT02285179
Recruitment Status : Recruiting
First Posted : November 6, 2014
Last Update Posted : December 8, 2017
Sponsor:
Collaborators:
Genentech, Inc.
EurocanPlatform
Rather
Information provided by (Responsible Party):
The Netherlands Cancer Institute

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: GDC-0032 Drug: Tamoxifen Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 290 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: double blinded study
Primary Purpose: Treatment
Official Title: Phase I/Prospective Randomized Phase II Trial Of the Safety and Efficacy of Tamoxifen in Combination With GDC-0032 Compared With Tamoxifen alONe.
Study Start Date : November 2014
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: tamoxifen and GDC-0032
20 mg tamoxifen QD and 4 MG GDC-0032 QOD
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

Placebo Comparator: tamoxifen and placebo
20 mg tamoxifen QD and placebo QOD
Drug: Tamoxifen
daily dose of 20 mg




Primary Outcome Measures :
  1. Number of patients with MTD toxicity [ Time Frame: 4 weeks ]
    MTD toxicity will be assessed in the first 28 days of treatment


Secondary Outcome Measures :
  1. Safety Number of patients with adverse events [ Time Frame: 2 year ]
    Number of patients with adverse events

  2. Pharmacokinetics Number of patients with germline DNA sequence [ Time Frame: 12 months ]
    Number of patients with germline DNA sequence

  3. Response Number of patients with a response to protocol treatment [ Time Frame: 2 year ]
    Number of patients with a response to protocol treatment



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02285179


Contacts
Contact: Sabine Linn, MD, PhD 003120512 ext 9111 s.linn@nki.nl
Contact: Annelot van Rossum, phd 003120512 ext 2004 a.v.rossum@nki.nl

Locations
France
Gustave Roussy Not yet recruiting
Paris, France
Principal Investigator: Mahasti Saghatchian, MD         
Netherlands
Antoni van Leeuwenhoek Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: Sabine C Linn, MD    +3120512 ext 2951    s.linn@nki.nl   
Contact: Annelot van Rossum, PhD    +3120512 ext 2004    a.v.rossum@nki.nl   
Principal Investigator: Sabine C Linn, MD         
Reinier de Graaf Gasthuis Recruiting
Delft, Netherlands
Contact: K. Beelen, MD, PhD         
Principal Investigator: K. Beelen, MD, PhD         
Haaglanden Medisch Centrum Recruiting
Den Haag, Netherlands
Contact: R. Oosterkamp, MD, PhD         
Principal Investigator: R. Oosterkamp, MD, PhD         
Deventer Ziekenhuis Recruiting
Deventer, Netherlands
Contact: A. Imholz, MD, PhD         
Principal Investigator: A. Imholz, MD, PhD         
Ziekenhuis Groep Twente Recruiting
Hengelo, Netherlands
Contact: E. Siemerink, MD, PhD         
Principal Investigator: E. Siemerink, MD, PhD         
MUMC Recruiting
Maastricht, Netherlands
Contact: M. de Boer, MD, PhD         
Principal Investigator: M. de Boer, MD, PhD         
Spain
Hospital Germans Trias i Pujol Recruiting
Badalona, Spain
Contact: M. Margeli Vila, MD, PhD         
Principal Investigator: M. Margeli Vila, MD, PhD         
Vall d'Hebron University Hospital/VHIO Recruiting
Barcelona, Spain, 080035
Contact: Mafalda AM Oliviera, MD       moliveira@vhio.net   
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain
Contact: J. Garcia Corbacho, MD, PhD         
Principal Investigator: J. Garcia Corbacho, MD, PhD         
Hospital ICO-Hospitalet (Bellvitge) Recruiting
Barcelona, Spain
Contact: S. Pernas, MD, PhD         
Principal Investigator: S. Pernas, MD, PhD         
Hospital Arnau de Vilanova Recruiting
Lleida, Spain
Contact: S. Morales Murillo, MD, PhD         
Principal Investigator: S. Morales Murillo, MD, PhD         
Hospital Universitari Sant Joan de Reus Recruiting
Tarragona, Spain
Contact: K. Amillano, MD, PhD         
Principal Investigator: K. Amillano, MD, PhD         
United Kingdom
University of Cambridge Recruiting
Cambridge, United Kingdom, CB20QQ
Contact: Richard D Baird, MA MRCP PhD    +44122376 ext 8434    rdb39@medschl.cam.ac.uk   
Sponsors and Collaborators
The Netherlands Cancer Institute
Genentech, Inc.
EurocanPlatform
Rather
Investigators
Principal Investigator: Sabine C. Linn, prof.dr. NKI-AvL
Study Chair: Richard Baird, dr Cambridge University

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02285179     History of Changes
Other Study ID Numbers: M14POS
First Posted: November 6, 2014    Key Record Dates
Last Update Posted: December 8, 2017
Last Verified: September 2017

Keywords provided by The Netherlands Cancer Institute:
GDC-0032
Pi3K inhibitor
tamoxifen
hormone receptor positive
RECIST
pharmacodynamic

Additional relevant MeSH terms:
Tamoxifen
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents