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Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma

Primary Purpose

Thymic Carcinoma

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Milciclib Maleate

About this trial

This is an interventional treatment trial for Thymic Carcinoma focused on measuring B3 and C malignant thymoma

Eligibility Criteria

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

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

Sites / Locations

TGen Clinical Research Services at Scottsdale Healthcare
NIH, Center for Cancer Research, Medical Oncology
Hopital Larrey
Institut de cancerologie Gustave Roussy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Azienda Ospedaliera San Luigi Gonzaga

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Milciclib Maleate (PHA-848125AC)

Arm Description

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

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

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.

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.

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.

Duration of Response

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

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.

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.

Full Information

NCT ID

NCT01011439

First Posted

November 10, 2009

Last Updated

January 22, 2019

Sponsor

Tiziana Life Sciences LTD

1. Study Identification

Unique Protocol Identification Number

NCT01011439

Brief Title

Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Terminated

Why Stopped

For the 2 last patients still on treated nominal therapeutic use of the Milciclib was approved at INT Milano.

Study Start Date

February 22, 2010 (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

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thymic Carcinoma

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

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Milciclib Maleate (PHA-848125AC)

Arm Type

Experimental

Arm Description

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

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

Confirmed Objective Response Rate (ORR)

Description

Time Frame

Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD.

Title

Disease Control Rate

Description

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.

Time Frame

Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD.

Title

Progression-free Survival

Description

Time Frame

Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD.

Title

Duration of Response

Description

Assessed 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 to a maximum duration of 242 weeks or until PD.

Title

Overall Survival

Description

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.

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

Overall Safety Profile (Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters)

Description

Time Frame

Adverse events: from date treatment consent signed to 28 days after last dose of study drug; hematology/blood chemistry tests: at baseline and between Day 11-14 of each cycle of a total of 135 two-week cycles.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials: