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Study Of Oral PHA-848125AC In Patients With Malignant Thymoma Previously Treated With Multiple Lines Of Chemotherapy

Primary Purpose

Malignant Thymoma

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Milciclib Maleate
Sponsored by
Tiziana Life Sciences LTD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Thymoma focused on measuring B3 and C malignant thymoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed and dated IRB/Approved Informed Consent
  • Histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma recurrent or progressing after more than one prior systemic therapy for advanced / metastatic disease
  • Presence of measurable disease
  • Age >=18 years old
  • 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 (with the exception of myasthenia gravis), 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

Sites / Locations

  • MedStar Georgetown University Hospital
  • NIH, Center for Cancer Research, Medical Oncology
  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Milciclib

Arm Description

Milciclib Maleate capsules

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
Duration of Response
Calculated in patients achieving a confirmed objective tumor response by RECIST version 1.1 criteria.
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.
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.

Full Information

First Posted
February 15, 2011
Last Updated
January 22, 2019
Sponsor
Tiziana Life Sciences LTD
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1. Study Identification

Unique Protocol Identification Number
NCT01301391
Brief Title
Study Of Oral PHA-848125AC In Patients With Malignant Thymoma Previously Treated With Multiple Lines Of Chemotherapy
Official Title
Phase II Study Of Oral PHA-848125AC In Patients With Malignant Thymoma Previously Treated With Multiple Lines Of Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Why Stopped
For the last patient still on treated nominal therapeutic use of the Milciclib was approved at INT Milano.
Study Start Date
February 2, 2011 (Actual)
Primary Completion Date
May 31, 2017 (Actual)
Study Completion Date
December 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tiziana Life Sciences LTD

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Thymoma
Keywords
B3 and C malignant thymoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Milciclib
Arm Type
Experimental
Arm Description
Milciclib Maleate capsules
Intervention Type
Drug
Intervention Name(s)
Milciclib Maleate
Other Intervention Name(s)
PHA-848125AC
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free Survival Rate at 3 Months
Description
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
Secondary Outcome Measure Information:
Title
Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters
Description
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.
Title
Objective Response Rate (ORR)
Description
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.
Title
Disease Control Rate (ORR+SD Rate)
Description
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.
Time Frame
Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
Title
Duration of Response
Description
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.
Title
Overall Survival
Description
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.
Title
Progression-free Survival (PFS)
Description
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed and dated IRB/Approved Informed Consent Histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma recurrent or progressing after more than one prior systemic therapy for advanced / metastatic disease Presence of measurable disease Age >=18 years old 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 (with the exception of myasthenia gravis), 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arun Rajan, MD.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marina C. Garassino, MD.
Organizational Affiliation
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Giuseppe Giaccone, MD
Organizational Affiliation
MedStar Gergetown University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
NIH, Center for Cancer Research, Medical Oncology
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
City
Milano
State/Province
(mi)
ZIP/Postal Code
20133
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

Study Of Oral PHA-848125AC In Patients With Malignant Thymoma Previously Treated With Multiple Lines Of Chemotherapy

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