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Breast CancerPhase 1/2PoseidonNCT02285179

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

A Phase 1/2 study testing GDC-0032 and Tamoxifen in people with Breast Cancer, run by The Netherlands Cancer Institute at 14 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
GDC-0032 and Tamoxifen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
189 participants
Where
14 sitesin 4 countries
Study dates
Nov 2014to 1 May 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

14 sites in 4 countries.

14 sites in 4 countries

Netherlands6 sites

  • Antoni van Leeuwenhoek

    Amsterdam, 1066 CX

  • Reinier de Graaf Gasthuis

    Delft

  • Deventer Ziekenhuis

    Deventer

  • Ziekenhuis Groep Twente

    Hengelo

  • MUMC

    Maastricht

  • Haaglanden Medisch Centrum

    The Hague

Other trials in Netherlands

Spain6 sites

  • Hospital Germans Trias i Pujol

    Badalona

  • Vall d'Hebron University Hospital/VHIO

    Barcelona, 080035

  • Hospital Clínic de Barcelona

    Barcelona

  • Hospital ICO-Hospitalet (Bellvitge)

    Barcelona

  • Hospital Arnau de Vilanova

    Lleida

  • Hospital Universitari Sant Joan de Reus

    Tarragona

Other trials in Spain

France1 site

  • Gustave Roussy

    Paris

Other trials in France

United Kingdom1 site

  • University of Cambridge

    Cambridge, CB20QQ

Other trials in United Kingdom

About this study

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.

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.

Read the 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

Conditions
Breast Cancer
Being tested
GDC-0032, Tamoxifen
Keywords
GDC-0032, Pi3K inhibitor, tamoxifen, hormone receptor positive, RECIST, pharmacodynamic
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GDC-0032Drug

    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

  • TamoxifenDrug

    daily dose of 20 mg

Study groups in NCT02285179
Study groupRoleWhat they receive
tamoxifen and GDC-0032Experimental20 mg tamoxifen QD and 4 MG GDC-0032 QOD
Receives: Drug: GDC-0032; Drug: Tamoxifen
tamoxifen and placeboPlacebo comparator20 mg tamoxifen QD and placebo QOD
Receives: Drug: Tamoxifen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients with MTD toxicity

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

    Measured: 4 weeks

Secondary outcomes (3)

  1. Safety Number of patients with adverse events

    Number of patients with adverse events

    Measured: 2 year

  2. Pharmacokinetics Number of patients with germline DNA sequence

    Number of patients with germline DNA sequence

    Measured: 12 months

  3. Response Number of patients with a response to protocol treatment

    Number of patients with a response to protocol treatment

    Measured: 2 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2014 (estimated)
  2. Study startNov 2014
  3. Primary completion1 May 2022
  4. Study completion1 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
189 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02285179
Sponsor's protocol ID
M14POS
Acronym
Poseidon
Status last verified
Oct 2022
First submitted
21 Oct 2014
Last updated
12 Oct 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GDC-0032 and Tamoxifen in people with Breast Cancer, run by The Netherlands Cancer Institute at 14 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Netherlands, Spain, France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with MTD toxicity (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02285179.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022.

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