Abstract OT2-07-06: Phase Ib study to assess the safety, tolerability, and clinical activity of gedatolisib in combination with palbociclib and either letrozole or fulvestrant in women with metastatic or locally advanced/recurrent breast cancer (B2151009)

Author(s):  
A Forero ◽  
HS Han ◽  
EC Dees ◽  
R Wesolowski ◽  
A Bardia ◽  
...  
2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1113-TPS1113 ◽  
Author(s):  
Andres Forero-Torres ◽  
Robert Wesolowski ◽  
Aditya Bardia ◽  
Haresh S. Jhangiani ◽  
Peter Kabos ◽  
...  

TPS1113 Background: Hormone receptor positive (HR+) disease is the most common subset of both early and late stage breast cancer (BC). The majority of women with HR+ metastatic BC (MBC) ultimately develop resistance to endocrine therapy, with a median survival of ~2-3 years. A new standard-of-care strategy to treat HR+ metastatic disease involves the combination of hormone therapy and cyclin-dependent kinase (CDK) 4/6 inhibition, which has demonstrated improved progression-free survival (PFS) in both the first- and later-line metastatic setting. More recently, preclinical data with the dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor gedatolisib (PF-05212384) suggest synergy with the combination of hormone therapy, CDK 4/6 inhibition, and inhibition of the PI3K/mTOR pathway. Methods: This phase Ib study includes a dose escalation portion to evaluate dose-limiting toxicities (primary endpoint) and determine the recommended phase II dose for triplet therapy with gedatolisib combined with palbociclib/letrozole or palbociclib/fulvestrant in women with HR+ HER2-negative MBC or locally advanced/recurrent BC, in the first- and later-line setting. Thereafter, a 3-arm expansion for early signals of efficacy will investigate objective response rates (primary endpoint) with gedatolisib combined with palbociclib/letrozole (n = 26), palbociclib/fulvestrant in patients without prior CDK 4/6 inhibition (n = 28), and palbociclib/fulvestrant in patients who have previously received palbociclib (n = 27). The rates of objective response will be compared to historical controls. Secondary endpoints include safety, tumor response, PFS (expansion portion only), pharmacokinetics, and biomarker correlations associated with the PI3K/mTOR pathway. This trial is now recruiting. Clinical trial information: NCT02684032.


2021 ◽  
Author(s):  
Taiju Shimbo ◽  
Mio Nakata ◽  
Hiroto Yoshioka ◽  
Chikara Sato ◽  
Akihiro Hori ◽  
...  

Abstract PurposeKochi Oxydol-Radiation Therapy for Unresectable Carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in clinical use in Japan. Its use sensitizes tumors to radiation by injecting hydrogen peroxide into the tumors to neutralize antioxidant enzymes and, simultaneously, increase intratumor oxygen tension. KORTUC II has achieved significant local effects with no notable adverse events. We report on the cases where KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC).Methods and MaterialsThirty patients treated with KORTUC II for LABC (n = 9) or LRBC (n = 21), who were followed up for at least 3 months after treatment, were included in the study. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide by volume. The mixture was injected intratumorally several times during the treatment period under ultrasound guidance, just before RT doses. RT was administered for local control. The irradiation dose and extent fields were determined by the attending physicians considering patient factors. Maximum tumor shrinkage (MTS) was measured by Computed Tomography. The duration of loco-regional control (LC) and progression free survival (PFS) after the completion of RT were determined using the Kaplan–Meier method.ResultsThe median irradiation dose was 60.4 Gy3.5 (43.6–76.1 Gy3.5) based on the calculation of EQD2, and median total number of sensitizer treatments was 5 (2–7). The median MTS was 97.0%. Fifteen patients (50%) were assessed to have achieved a clinical complete response. The proportion of patients with LC at 1, 2, and 3 years was 100%, 94.7%, and 75.4%. The proportion with PFS after RT at 1 and 2 years was 59.0%, and 24.1%, respectively.ConclusionsKORTUC II treatment demonstrated high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and extremely promising RT with an excellent radio-sensitizing effect.Trial registrationOsaka Medical College Clinical Trials Registry, trial no. 1973, date. May 10, 2010UMIN Clinical Trials Registry, trial no. UMIN000003734, date. June 10, 2010


1989 ◽  
Vol 76 (6) ◽  
pp. 559-563 ◽  
Author(s):  
R. J. L. Williams ◽  
I. J. C. Fryatt ◽  
W. C. Abbott ◽  
H. White

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