The intent of the study is to assess the antitumor activity of PHA-848125AC in patients with recurrent or metastatic, unresectable malignant thymoma previously treated with multiple lines of chemotherapy.
This is a single-arm, open-label, multicenter, phase II clinical trial design with an early stopping rules. PHA-848125AC will be administered to patients with recurrent metastatic unresectable B3 thymoma or thymic carcinoma who have received more than one line of prior systemic therapy for advanced / metastatic disease. The intent of the study is to assess the antitumor activity of PHA-848125AC and ultimately to improve the outcome of the patients. The primary end point for this study is a progression free survival rate of 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle. Number of cycles: until disease progression or unacceptable toxicity.
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
NIH, Center for Cancer Research, Medical Oncology
Bethesda, Maryland, United States
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milan, (mi), Italy
Progression-free Survival Rate at 3 Months
The proportion of successes (i.e. patients alive and progression-free at 3 months since treatment start) out of the total number of evaluable patients.
Time frame: 3 months since treatment start
Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters
The adverse events (AEs) were coded with the Medical Dictionary for Regulatory Activities (MedDRA) and their severity graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The following subsets of AEs were considered: serious AEs, AEs with CTCAE grade 3-5, AEs with a relationship to study treatment classified by the Investigator as possible or probable or definite and AEs reported as leading to discontinuation from treatment. Laboratory test values were graded according to the NCI CTCAE scale, v3.0, whenever possible. For each laboratory test included in the NCI CTCAE system, the incidence of abnormalities were evaluated by considering the worst occurrence for each patient throughout the whole treatment period.
Time frame: Adverse events: from date treatment consent signed to 28 days after last treatment; hematology/blood chemistry tests: at baseline and between Day 11-14 of each cycle of a maximum total of 48 two-week cycles.
Objective Response Rate (ORR)
Point and 95% confidence interval estimates was calculated for the objective tumor response rate (confirmed CRs or PRs). The determination of antitumor efficacy was based on objective tumor assessments made according to the RECIST guideline (version 1.1). The analysis was performed in the evaluable population.
Time frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
Disease Control Rate (ORR+SD Rate)
Point and 95% confidence interval estimates was calculated for the disease control rate (confirmed CRs / PRs and SD \> or = 6 weeks). The analysis was performed in the evaluable patient populations.
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Time frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
Duration of Response
Calculated in patients achieving a confirmed objective tumor response by RECIST version 1.1 criteria.
Time frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
Overall Survival
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, and to the date in which the patients diagnosed with the disease are still alive. Kaplan-Meier estimates as percentage of patients alive.
Time frame: Every 6 weeks during Follow-Up until PD or new therapy start; every 6 months thereafter, up to 2 years from the last dose of study drug.
Progression-free Survival (PFS)
The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.
Time frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.