Clinical trial NCT01011439: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Thymic Carcinoma
Keywords: B3 and C malignant thymoma
Lead sponsor: Tiziana Life Sciences LTD
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival Rate at 3 Months
timeFrame: 3 months since treatment start
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR)
timeFrame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD.
measure: Disease Control Rate
timeFrame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD.
measure: Progression-free Survival
timeFrame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD.
measure: Duration of Response
timeFrame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD.
measure: Overall Survival
timeFrame: 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.
measure: Overall Safety Profile (Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters)
timeFrame: 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.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TGen Clinical Research Services at Scottsdale Healthcare
state: Arizona
city: Bethesda
country: United States
facility: NIH, Center for Cancer Research, Medical Oncology
state: Maryland
city: Toulouse Cedex
country: France
facility: Hopital Larrey
city: Villejuif Cedex
country: France
facility: Institut de cancerologie Gustave Roussy
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
state: (mi)
city: Orbassano
country: Italy
facility: Azienda Ospedaliera San Luigi Gonzaga
Study officials:
affiliation: Scottsdale Clinical Research Institute, USA
name: Glen Weiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Gustave Roussy, Villejuif, France
name: Benjamin Besse, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hopital Larrey CHU, Toulouse, France
name: Julien Mazières, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale San Luigi Gonzaga, Orbassano, Italy
name: Silvia Novello, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute (NCI)
name: Arun Rajan, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
name: Marina C Garassino, MD
role: PRINCIPAL_INVESTIGATOR
References: