Non-inferiority of partial breast irradiation (PBI) and concurrent compared to sequential
chemotherapy with respect to acute grade 3-4 radiation toxicity.
To examine whether aging increases human mammary stem/progenitor cells (MaSC) with aberrant phenotypes and if rapamycin can reduce malignant markers and MaSC number in surgical specimens.
To compare the effect of a supervised weight loss intervention plus health education materials versus health education materials alone upon invasive disease free survival (iDFS) in overweight (BMI 27-29.9 kg/m2) and obese (BMI 30kg/m2) women diagnosed with HER-2 negative, stage II and III breast cancer.
To determine the relationship between changes in weight and iDFS, and to explore interaction between the level of clinical benefit from weight loss and the intervention.
To evaluate the effect of a supervised weight loss intervention upon:
a) Overall survival
b) Distant disease free survival
d) Body composition (as measured by waist and hip circumference)
e) Insulin Resistance Syndrome associated conditions diabetes, hospitalization for
To determine the impact of a supervised weight loss intervention on IDFS within subgroups
of women with 1) hormone receptor positive breast cancer and 2) hormone receptor negative
To determine the impact of a supervised weight loss intervention on IDFS within subgroups of 1) premenopausal women and 2) post-menopausal women.
Primary: To assess the antitumor activity of lurbinectedin (PM01183) in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, in the following advanced solid tumors: small cell lung cancer (SCLC), head and neck carcinoma (H&N), neuroendocrine tumors (NETs), biliary tract carcinoma, endometrial carcinoma, BRCA 1/2-associated metastatic breast carcinoma, carcinoma of unknown primary site, germ cell tumors (GCTs), and Ewing¿s family of tumors (EFTs). Secondary: To further characterize the antitumor activity of PM01183 in terms of duration of response (DR), clinical benefit [ORR or stable disease (SD) lasting over four months (SD ¿ 4 months)], progression-free survival (PFS), and one year overall survival (1y-OS) in each cohort of advanced solid tumors. Characterize the plasma pharmacokinetics (PK) of PM01183. To conduct an exploratory pharmacogenomic (PGx) and pharmacogenetic analysis. To evaluate the safety profile of PM01183 in this patient population.
For the Phase 1b part to determine safety and tolerability of eribulin mesylate in
combination with pembrolizumab in subjects with metastatic triple-negative breast cancer
previously treated with 0 to 2 lines of chemotherapy in the metastatic setting.
For the Phase 2 part to evaluate objective response rate, based on Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1, of eribulin mesylate in combination with
pembrolizumab in subjects with metastatic triple-negative breast cancer previously treated
with 0 to 2 lines of chemotherapy in the metastatic setting.
To evaluate Progression-Free Survival (PFS)
To evaluate Overall Survival (OS)
To evaluate Duration of Response (DOR)
To evaluate efficacy in a subset defined by PD-L1 (programmed death receptor-ligand 1)
To evaluate the safety and tolerability
To evaluate Clinical Benefit Rate (CBR)
To evaluate exposure-response relationship
To explore potential effects of pembrolizumab co-administration on the pharmacokinetics
(PK) of eribulin mesylate
To explore ORR, PFS, DOR, and CBR using the immune-related response criteria in solid