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Trial record 2 of 14 for:    gdc0032

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by The Netherlands Cancer Institute
Sponsor:
Collaborators:
Genentech, Inc.
EurocanPlatform
Rather
Information provided by (Responsible Party):
The Netherlands Cancer Institute
ClinicalTrials.gov Identifier:
NCT02285179
First received: October 21, 2014
Last updated: September 5, 2016
Last verified: September 2016
  Purpose

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 Intervention Phase
Breast Cancer
Ovarian Cancer
Cancer of the Uterus
Drug: GDC-0032
Drug: Tamoxifen
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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.

Resource links provided by NLM:


Further study details as provided by The Netherlands Cancer Institute:

Primary Outcome Measures:
  • Number of patients with MTD toxicity [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    MTD toxicity will be assessed in the first 28 days of treatment


Secondary Outcome Measures:
  • Safety Number of patients with adverse events [ Time Frame: 2 year ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events

  • Pharmacokinetics Number of patients with germline DNA sequence [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Number of patients with germline DNA sequence

  • Response Number of patients with a response to protocol treatment [ Time Frame: 2 year ] [ Designated as safety issue: No ]
    Number of patients with a response to protocol treatment


Estimated Enrollment: 32
Study Start Date: November 2014
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tamoxifen and GDC-0032
20 mg tamoxifen QD and dose escalation GDC-0032
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

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
  Eligibility

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

Inclusion criteria:

  • Minimum age for inclusion 18 years and a WHO performance status ≤ 2
  • Patients with metastatic or incurable locally advanced disease
  • Female patients with Breast cancer patients with ER and/or PR positive tumours In the phase 1b part of the study, breast cancer patients may have either HER2 negative or HER2 positive disease.
  • Patients with other cancer types are eligible if the investigator considers that they might benefit from endocrine therapy combined with PI3K inhibition
  • During the dose escalation phase 1b, patients may have either measurable or non-measurable disease by RECIST criteria
  • Archival tumour tissue is allowed, however fresh biopsies are desirable whenever feasible and accessible according to the investigator's judgment
  • Life expectancy ≥ 12 weeks.
  • adequate organ and marrow function
  • understanding and complying with the protocol requirements and has signed the informed consent document.
  • child bearing potential must have a negative serum or urine pregnancy test within 14 days prior to registration/randomisation, and must use an effective method of contraception during treatment and for at least 60 days after the final dose of study drug.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02285179

Contacts
Contact: Ingrid Mandjes 003120512 ext 2667 i.mandjes@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         
Spain
Vall d'Hebron University Hospital/VHIO Recruiting
Barcelona, Spain, 080035
Contact: Mafalda AM Oliviera, MD       moliveira@vhio.net   
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
  More Information

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02285179     History of Changes
Other Study ID Numbers: M14POS 
Study First Received: October 21, 2014
Last Updated: September 5, 2016
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
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

ClinicalTrials.gov processed this record on September 28, 2016