Phase Ib/II Study of LY2780301 in Combination With Weekly PACLITAXEL in HER2-metastatic Breast Ca… (NCT01980277) | Clinical Trial Compass
TerminatedPhase 1/2
Phase Ib/II Study of LY2780301 in Combination With Weekly PACLITAXEL in HER2-metastatic Breast Cancer
Stopped: Drug development stopped
France68 participantsStarted 2014-01
Plain-language summary
The overall rationale of this study evaluating tolerance and efficacy of LY2780301 in combination with paclitaxel in HER2-negative, inoperable locally advanced or metastatic breast cancer (MBC) is based on :
* the medical need in this population with either hormonal-resistant or unsensitive and/or rapidly progressive disease
* the preclinical evidences for involvement of PI3K/AKT pathway in tumor progression and drug resistance, including taxanes as well as its potential reversion by AKT inhibition
* the high level of frequency of PI3K/AKT activation in HER2-negative MBC
* the in vitro and in vivo preclinical activity of LY2780301, and its synergistic combination with various anticancer agents, including taxanes
* the favourable profile of tolerance of LY2780301 in phase I trial
Weekly paclitaxel is conventionally administered at 80 mg/m²/week and is a standard treatment in breast cancer (BC) As described above, LY2780301 500 mg once daily has been established as the RP2D in phase I single agent trial.
Evidence of pharmacodynamic activity was noted at 400-500 mg QD. Conservatively, the first dose level to be explored will be LY2780301 400 mg QD and paclitaxel 70 mg/m²/week.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Female or male patients (≥ 18 years)
✓. WHO/ECOG performance status ≤ 1 for phase Ib part, \< 2 for phase II part
✓. Patient with histologically confirmed inoperable locally advanced BC or MBC
✓. Patient with tumor biopsy from metastatic tissue containing more than 50% tumor cells
✓. Patient has known hormone receptor (ER/PR) status, positive and/or negative (local laboratory testing)
✓. Patient has HER2-negative disease: IHC 0, 1 + or 2+ and/or in situ hybridization (FISH, CISH, SISH) negative (local laboratory testing)
✓. Phase Ib: Patient has measurable or non-measurable disease according to RECIST 1.1 criteria only Phase II: Patient has measurable disease according to RECIST 1.1 criteria only
✓. Patient has adequate bone marrow and organ function
Exclusion criteria
✕. Previous treatment with AKT or PI3K inhibitor
What they're measuring
1
Phase Ib: recommended phase II dose (RP2D)
Timeframe: Day 28
2
Phase II: objective response rate (ORR)
Timeframe: until progression assessed up to 18 months
✕. no previous cytotoxic treatment for metastatic or inoperable locally advanced disease (phase II part); Adjuvant/neoadjuvant therapy will be counted as prior line of therapy for metastatic/recurrent disease if the patient had a progression/recurrence within 6 months after completion of the therapy (12 months for taxane-based therapy). Previous hormonal treatment for metastatic or locally advanced disease is allowed.
✕. Patient with bone metastases only
✕. Patient has symptomatic CNS metastases; patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 15 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have completed corticosteroid therapy.
✕. Patient has a concurrent malignancy or malignancy within 3 years of study enrollment
✕. Patient has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study
✕. Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C; 3 weeks for weekly chemotherapy) prior to starting study drug or who have not recovered from side effects of such therapy
✕. Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half-lives prior to starting study drug or who have not recovered from side effects of such therapy