Title

Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma
Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma Previously Treated With Chemotherapy
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    milciclib ...
  • Study Participants

    72
The intent of the study is to assess the antitumor activity of PHA-848125AC as second-line treatment in patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy.
The Simon's optimal 2 stage design is adopted for this single-arm, open-label, multicenter phase II clinical trial of PHA-848125AC administered to patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy (only one prior systemic therapy allowed). The intent of the study is to assess the antitumor activity of PHA-848125AC and ultimately to improve the outcome of patients with thymic carcinoma who have already exploited one chemotherapy option. The primary end point for this study is a progression free survival rate of 3 months.
Study Started
Feb 22
2010
Primary Completion
May 31
2017
Study Completion
Dec 17
2018
Results Posted
Oct 16
2018
Last Update
Feb 06
2019

Drug Milciclib Maleate

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.

  • Other names: PHA-848125AC

Milciclib Maleate (PHA-848125AC) Experimental

100 and 50 mg Capsule 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

Criteria

Inclusion Criteria:

Histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma recurrent or progressing after prior chemotherapy (only one prior systemic therapy allowed)
Presence of measurable disease
Age >=18 years
ECOG performance status 0-1
Negative pregnancy test (if female in reproductive years)
Use of effective contraceptive methods if men and women of child producing potential
Adequate liver function Total Serum Bilirubin <=1.5 x upper limit of normal (ULN) Transaminases (AST/ALT) <=2.5ULN (if liver metastases are present, then <=5ULN is allowed) ALP <=2.5ULN (if liver and/or bone metastases are present, then <=5ULN is allowed)
Adequate renal function Serum Creatinine <=ULN or Creatinine Clearance calculated by Cockcroft and Gault's formula > 60 mL/min.
Adequate hematologic status ANC >=1,500cells/mm3 Platelet Count >=100,000cells/mm3 Hemoglobin >=9.0g/dL
Two weeks must have elapsed since completion of prior chemotherapy, minor surgery, radiotherapy (provided that no more than 25% of bone marrow reserve has been irradiated)
Resolution of all acute toxic effects of any prior treatments to NCI CTC (Version 3.0) grade <=1

Exclusion Criteria:

Any of the following in the past 6 months: myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis
Grade >1 retinopathy
Known brain metastases
Known active infections
Pregnant or breast feeding women
Diabetes mellitus uncontrolled
Gastrointestinal disease that would impact on drug absorption
Patients under treatment with anticoagulants or with coagulation disorders or with signs of hemorrhage at baseline
Patients with previous history or current presence of neurological disorders, including epilepsy (although controlled by anticonvulsant therapy), Parkinson's disease and extra-pyramidal syndromes
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that make the patient inappropriate for entry into this study

Summary

Milciclib Maleate (PHA-848125AC)

All Events

Event Type Organ System Event Term Milciclib Maleate (PHA-848125AC)

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

Milciclib Maleate (PHA-848125AC)

Confirmed 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.

Milciclib Maleate (PHA-848125AC)

3.7
Percentage of patients
95% Confidence Interval: 0.45 to 12.75

Disease Control Rate

Point and 95% confidence interval estimates was calculated for the disease control rate (confirmed CRs / PRs and SD>/= 6 weeks). The analysis was performed in the evaluable populations.

Milciclib Maleate (PHA-848125AC)

75.9
Percentage of patients
95% Confidence Interval: 62.36 to 86.51

Progression-free Survival

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.

Milciclib Maleate (PHA-848125AC)

6.83
Months (Median)
95% Confidence Interval: 4.11 to 8.71

Duration of Response

Assessed in patients achieving a confirmed objective tumor response by RECIST version 1.1 criteria.

Milciclib Maleate (PHA-848125AC)

8.41
Months (Median)
95% Confidence Interval: 6.9 to 9.92

Overall Survival

The length of time from the start of treatment for a disease, such as cancer, to the date in which the patients diagnosed with the disease were still alive.

Milciclib Maleate (PHA-848125AC)

24.18
Months (Median)
95% Confidence Interval: 16.89 to 36.57

Overall Safety Profile (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 was evaluated by considering the worst occurrence for each patient throughout the whole treatment period.

Milciclib Maleate (PHA-848125AC)

N° patients with abnormal Blood Chemistry test

N° patients with abnormal Hematology test

N° patients with Adverse Events

Age, Continuous

53.2
years (Mean)
Standard Deviation: 13.3

Age, Categorical

Masaoka clinical staging at study entry

Race/Ethnicity, Customized

Region of Enrollment

Sex: Female, Male

Tumor extent at study entry

WHO - Classification

Overall Study

Milciclib Maleate (PHA-848125AC)

Drop/Withdrawal Reasons

Milciclib Maleate (PHA-848125AC)