To evaluate the incidence of Event-Free Survival at 12 months, where Event-Free Survival is defined as High-Grade-Recurrence Free Survival
The primary efficacy objective for this study is as follows:
¿ To evaluate the efficacy of adjuvant MPDL3280A treatment in patients with PD- L1¿selected muscle invasive bladder cancer (MIBC), as measured by disease-free survival (DFS)
The secondary efficacy objectives for this study are as follows:
¿ To evaluate the efficacy of adjuvant MPDL3280A treatment, as measured by overall survival (OS)
¿ To evaluate the efficacy of adjuvant MPDL3280A treatment, as measured by disease-specific survival (DSS)
¿ To evaluate the efficacy of adjuvant MPDL3280A treatment, as measured by distant metastasis-free survival (DMFS)
The safety objectives for this study are as follows:
¿ To evaluate the safety and tolerability of MPDL3280A in the adjuvant setting
¿ To evaluate the incidence of anti-therapeutic antibodies (ATAs) against MPDL3280A and to explore the potential relationship of the immunogenicity response with pharmacokinetics, safety, and efficacy
The pharmacokinetic (PK) objective for this study is as follows:
¿ To characterize the pharmacokinetics of MPDL32820A
Patient-Reported Outcome Objective
The patient-reported outcome (PRO) objective for this study is as follows:
¿ To assess health status as measured by the EuroQol 5-dimension, 5-level version (EQ-5D-5L) questionnaire
The exploratory objective for this study is as follows:
¿ To assess predictive, prognostic, and pharmacodynamic exploratory biomarkers in archival and/or fresh tumor tissue and blood and their association with disease recurrence
The primary country-specific objective is to evaluate the efficacy of MPDL3280A adjuvant treatment in patients who are residents of China, with PD-L1-selected MIBC after cystectomy, as measured by DFS.
There are no country-specific secondary objectives for the population of Chinese patients. Country¿specific exploratory objectives for the Chinese patient population are identical to the secondary efficacy, safety, PK, and PRO objectives specified above.
To evaluate the preventive effects of EGCG on colonic tissue in patients with resected colorectal cancer when compared to patients on observation.
After a baseline breast tumor core biopsy, eligible women with triple negative breast cancer (ER- alpha, PR and HER-2 receptor negative) will be treated with S-equol at a dose of 50 mg twice daily for a period of about 14 days (10-21 day range). After completion of treatment, a second breast tumor sample will be obtained to compare molecular changes between the two specimens. The second pathology specimen may be from the surgical resection of the breast tumor, or a repeat core needle biopsy, if no further surgery is planned. The primary endpoint will be the absolute change in the Ki67, which is a validated marker of tumor proliferation in breast cancer. Secondary endpoints will include assessment of total ER-beta and pY36 levels as measured by immunohistochemical staining and their correlation with S-equol effects. Further treatment after surgical resection or second core needle biopsy of the tumor will be guided by tumor size, nodal status and other standard parameters, and is at the discretion of the treating physician. The Investigator hypothesizes that S-equol will cause a measurable decrease in Ki-67 in estrogen receptor beta expressing triple negative breast cancers, indicating its potential efficacy in this tumor type.
1.1 Primary Aims
- To determine the tolerability of brentuximab vedotin given in combination with standard chemotherapy (ALCL99) and to determine the tolerability of crizotinib given in combination with chemotherapy (ALCL99).
1.1.2 Event Free Survival
-To estimate the Event Free Survival (EFS) of Arm BV and Arm CZ and contrast these to historical control data.
1.2 Secondary Aim
- To determine the prognostic significance of minimal disseminated disease (MDD) at diagnosis and minimal residual disease (MRD) as measured by RT- polymerase chain reaction (PCR) in peripheral blood.