Abstract PS11-33: A first-in-human Phase 1/1b multicenter, open-label dose escalation study to assess safety and tolerability of PMD-026, a first-in-class oral RSK inhibitor, in metastatic breast cancer patients

Author(s):  
Murali Beeram ◽  
Judy S. Wang ◽  
Pavani Chalasani ◽  
Lida Mina ◽  
Amita Patnaik ◽  
...  
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3089-3089
Author(s):  
Ateeq Ahmad ◽  
S. Sheikh ◽  
R. Nagarkar ◽  
J. K. Singh ◽  
S. Krishnan ◽  
...  

3089^ Background: Endoxifen is an active metabolite of tamoxifen, a drug used in the treatment of breast cancer. To be clinically effective, tamoxifen must be converted to endoxifen by CYP2D6. Direct administration of endoxifen would not be subject to pharmacogenetic variations or drug-drug interactions. Our preclinical studies (Breast Cancer Treat 122, 579-584, 2010) have validated the concept of using endoxifen for the treatment of breast cancer. In human (Clin. Pharmacol. Ther. 88, 814-817, 2010), the single oral doses tested up to 4 mg of endoxifen were safe, well tolerated and bioavailable. Methods: A multiple-dose escalating study was conducted in 3 cohorts and each cohort had 6 patients (18 metastatic breast cancer patients). Endoxifen at 3 dose levels (2, 4, or 8 mg) was given once daily for 28 days. Routine laboratory tests, vital signs and electrocardiograms were measured throughout the study. Blood samples for PK analysis were collected after 28 days post dose. Endoxifen in plasma samples was determined using LC-MS/MS. Results: Endoxifen was found to be safe up to 8.0 mg. At steady state, it displays dose-proportional PK with respect to Cmax and AUC ( see Table below). Conclusions: Multiple daily endoxifen doses of 4.0-8.0 mg resulted in endoxifen exposures that would be sufficient for effective therapy. The favorable safety and multiple-dose PK profile of endoxifen warrants further evaluation of safety and efficacy of endoxifen in breast cancer patients. [Table: see text]


2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Wendy Painter ◽  
April L. Speed ◽  
Kiwita Phillips ◽  
Priscilla Pemu ◽  
Alice Robertson ◽  
...  

99 Background: Breast cancer patients taking tamoxifen (TAM) or an aromatase inhibitor (AI) often develop severe vasomotor symptoms (VMS) yet the only FDA approved non-hormonal treatment for VMS, 7.5 mg paroxetine, has a warning against concomitant use with TAM. Q-122, an orally-available small molecule, is being developed to address this unmet medical need. Results from the Phase 1b study, Q-1001, are presented. Methods: Q-1001 was a Phase 1 open-label, two-dose, dose-escalation study of the safety and preliminary effectiveness of Q-122 in females with breast cancer currently taking TAM or an AI and experiencing an average of at least 7-8 moderate to severe hot flashes per day. Key exclusion criteria included significant renal or hepatic disease, untreated hyperthyroidism and clinically significant abnormal laboratory findings. The study period included a 2 week drug-free screening phase, 28 day treatment phase, and 2 week drug-free follow-up period. Subjects were initially enrolled into Group 1 (100 mg Q-122) followed by Group 2 (200 mg Q-122). Safety was assessed by review of adverse events (AEs), physical findings and laboratory values. The primary efficacy endpoints were mean changes in frequency and severity (hot flash severity score, HFSS) of moderate and severe hot flashes from baseline to Week 4. Menopausal symptoms were assessed using the Greene Climacteric Scale (GCS). Results: 10 and 11 subjects received 100 and 200 mg Q-122 respectively; 8 subjects in each group completed the study. At the end of treatment for groups 1 and 2 respectively, the daily average frequency of hot flashes was reduced from 9.9 to 4.1 and from 8.6 to 3.2, and the mean HFSS was reduced by 62% and 68% from baseline values. Menopausal symptoms assessed using the GCS were significantly reduced from baseline (psychological: -82%; somatic: -65%; vasomotor: -65%). All AEs (n = 29) were either mild (79%) or moderate (21%) in severity and only 3 (all in one subject) were considered possibly related to study drug. Conclusions: Treatment with Q-122 resulted in significant reduction in the frequency and severity of VMS and improvement in menopausal symptoms as assessed by the GCS. No safety issues associated with the use of Q-122 were identified in this study.


2010 ◽  
Vol 1 (1) ◽  
pp. 45-49
Author(s):  
AKIHIKO OSAKI ◽  
SHOSHU MITSUYAMA ◽  
JUN-ICHI KUREBAYASHI ◽  
HIROSHI SONOO ◽  
REIKI NISHIMURA ◽  
...  

2006 ◽  
Vol 9 (S1) ◽  
pp. 172-205
Author(s):  

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Spanish Breast Cancer Research Group (GEICAM). Clinical trials include: FAC versus CMF as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. GEICAM/8701Phase III study of concomitant versus sequential chemohormonotherapy (EC plus tamoxifen) as adjuvant chemotherapy for node-positive postmenopausal women. GEICAM/9401High-dose DICEP chemotherapy versus observation in metastatic breast cancer patients with monotopic disease responding to induction chemotherapy with paclitaxel plus epirubicin. Phase III GEICAM trial. GEICAM/9601Vinorelbine infusion over 96 hours in heavily pre-treated patients with metastatic breast cancer: a cooperative study by the GEICAM group. GEICAM/9702Phase II trial of gemcitabine in combination with vinorelbine in patients with metastatic breast cancer resistant to anthracyclines. GEICAM/9704A phase II trial for evaluation of sequential doxorubicin and docetaxel as first-line treatment in metastatic breast cancer. GEICAM/9801A multicenter phase III randomized trial comparing docetaxel with doxorubicin and cyclophosphamide (TAC) versus 5-fluorouracil with doxorubicin and cyclophosphamide (FAC) as adjuvant treatment of operable breast cancer patients with negative axillary lymph nodes. TARGET 0 / GEICAM/9805A multicenter phase III randomized trial to compare the sequential and the concomitant administration of doxorubicin and docetaxel, as first-line chemotherapy treatment for metastatic breast disease. GEICAM/9903Docetaxel plus gemcitabine administered every other week as first-line treatment for metastatic breast cancer. GEICAM/9904Weekly docetaxel as neo-adjuvant treatment in stage II and III breast cancer. GEICAM/9905A multicenter phase III randomized trial comparing 5-fluorouracil with epirubicin and cyclophosphamide (FEC) versus 5-fluorouracil with epirubicin and cyclophosphamide (FEC) followed by weekly paclitaxel as adjuvant treatment of operable breast cancer patients with positive axillary lymph nodes. GEICAM/9906An open, multicenter randomized phase IV trial for the administration of pamidronate to breast cancer patients with bone metastatic disease. GEICAM/2000-01A randomized phase III treatment to compare the administration of vinorelbine versus vinorelbine plus gemcitabine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes. GEICAM/2000-04Maintenance phase III/IV study for the administration of Caelyx versus no treatment, after induction chemotherapy for metastatic breast cancer disease. GEICAM/2001-01A multicenter, cross-over, randomized trial with exemestane versus anastrozole as first-line hormonal treatment of postmenopausal women with metastatic breast cancer disease and positive hormone receptors. GEICAM/2001-03A multicenter, open-label randomized phase III trial for the administration of zoledronate to patients with advanced breast cancer disease and non-symptomatic bone metastasis. GEICAM/2001-05A multicenter phase II trial to evaluate the administration of gemcitabine with doxorubicin and paclitaxel (GAT) as neo-adjuvant treatment of stage III disease breast cancer patients. GEICAM/2002–01A phase II trial to evaluate the administration of doxorubicin with cyclophosphamide (AC) followed by weekly docetaxel (T) as neo-adjuvant treatment of stage II disease breast cancer patients. GEICAM/2002–03A multicenter, open-label, randomized phase III trial comparing six courses of FAC (fluorouracil, doxorubicin, cyclophosphamide) with four courses of FAC followed by 8-weekly administrations of Taxol in the adjuvant treatment of node-negative patients with operable breast cancer. GEICAM/2003–02A multicenter, open-label, randomized phase III trial comparing epirubicin plus cyclophosphamide (EC) followed by docetaxel (T) with epirubicin plus docetaxel (ET) followed by capecitabine (X) in the adjuvant treatment of node-positive patients with operable breast cancer. GEICAM/2003–10Open-label, no randomized, phases I–II of the treatment with Myocet/Taxotere/Herceptin as primary antineoplasic treatment in newly diagnosed breast cancer patients with HER2neu overexpression. GEICAM/2003–03Phase IV.II clinical trial with the combination of pegylated liposomal doxorubicin, cyclophosphamide and trastuzumab in patients with metastatic breast cancer with overexpression HER2neu. GEICAM/2004–05Randomized clinical trial to compare the benefit of adding trastuzumab to the combination of capecitabine plus vinorelbine as second-line treatment for patients with locally advanced non-operable breast cancer or metastatic breast cancer with overexpression of HER2, who have progressed to a previous line of treatment for metastatic disease that included trastuzumab in combination with taxanes. GEICAM/2004–06Phase IV.II clinical trial, multicenter, for administration of capecitabine concomitant to radiotherapy in patients with locally advanced breast cancer and HER2neu negatives. GEICAM/2005–01Phase IV.III, multicenter, open, randomized treatment study to evaluate the efficacy of maintenance therapy with capecitabine after standard chemotherapy with anthracyclines in patients with metastatic breast cancer. GEICAM/2005–04


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