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

Purpose

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.

Condition	Intervention	Phase
Thymic Carcinoma	Drug: Milciclib Maleate	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma Previously Treated With Chemotherapy

Further study details as provided by Tiziana Life Sciences, PLC:

Primary Outcome Measures:

Progression-free survival rate at 3 months [ Time Frame: 3 months since treatment start ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall safety profile [ Time Frame: All cycles from enrollment to 28 days after last treatment ] [ Designated as safety issue: Yes ]
Assessment of additional measures of tumor control to further characterize the efficacy profile of PHA-848125AC [ Time Frame: Every 6 weeks during the entire study ] [ Designated as safety issue: No ]
Explorative baseline characterization of biomarkers in tumor tissue of consenting patients [ Time Frame: Baseline ] [ Designated as safety issue: No ]


Enrollment:	60
Study Start Date:	March 2009
Estimated Study Completion Date:	March 2019
Estimated Primary Completion Date:	March 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Milciclib Maleate (PHA-848125AC) 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	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 Name: PHA-848125AC

Detailed Description:

The Simon's optimal 2 stage design is adopted for this single-arm, open-label, multicentre 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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011439

Locations


United States, Arizona
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, Maryland
NIH, Center for Cancer Research, Medical Oncology
Bethesda, Maryland, United States, 20892
France
Hopital Larrey
Toulouse Cedex, France, 31059
Institut de cancerologie Gustave Roussy
Villejuif Cedex, France, 94805
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milano, (mi), Italy, 20133
Azienda Ospedaliera San Luigi Gonzaga
Orbassano, Italy, 10043

Sponsors and Collaborators

Tiziana Life Sciences, PLC

Investigators


Study Director:	Anna Petroccione, MD	CLIOSS (Nerviano Medical Sciences Group), Italy
Principal Investigator:	Glen Weiss, MD	Scottsdale Clinical Research Institute, USA
Principal Investigator:	Benjamin Besse, MD	Institut Gustave Roussy, Villejuif, France
Principal Investigator:	Julien Mazières, MD	Hopital Larrey CHU, Toulouse, France
Principal Investigator:	Silvia Novello, MD	Ospedale San Luigi Gonzaga, Orbassano, Italy
Principal Investigator:	Arun Rajan, MD.	National Cancer Institute (NCI)
Principal Investigator:	Marina C Garassino, MD	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

More Information


Responsible Party:	Tiziana Life Sciences, PLC
ClinicalTrials.gov Identifier:	NCT01011439 History of Changes
Other Study ID Numbers:	CDKO-125a-006 2009-014338-79
Study First Received:	November 10, 2009
Last Updated:	May 4, 2016
Health Authority:	United States: Food and Drug Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Italy: The Italian Medicines Agency

Keywords provided by Tiziana Life Sciences, PLC:


B3 and C malignant thymoma

Additional relevant MeSH terms:


Carcinoma Thymoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Complex and Mixed Thymus Neoplasms	Thoracic Neoplasms Neoplasms by Site Lymphatic Diseases Maleic acid Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2016