Clinical Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen
Conditions
Breast Cancer - Ovarian Cancer - Cancer of the Uterus
Conditions: official terms
Uterine Neoplasms
Conditions: Keywords
GDC-0032, Pi3K inhibitor, tamoxifen, hormone receptor positive, dose escalation, RECIST, pharmacodynamic
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: GDC-0032 Type: Drug
Name: Tamoxifen Type: Drug
Overall Status
Recruiting
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
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Female
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
Locations
Antoni van Leeuwenhoek
Amsterdam, Netherlands
Status: Recruiting
Contact: Sabine C Linn, MD - +3120512 - s.linn@nki.nl
Vall d'Hebron University Hospital/VHIO
Barcelona, Spain
Status: Recruiting
Contact: Mafalda AM Oliviera, MD - moliveira@vhio.net
University of Cambridge
Cambridge, United Kingdom
Status: Recruiting
Contact: Richard D Baird, MA MRCP PhD - +44122376 - rdb39@medschl.cam.ac.uk
Start Date
November 2014
Completion Date
July 2015
Sponsors
The Netherlands Cancer Institute
Source
The Netherlands Cancer Institute
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page