Clinical trial NCT01301391: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Malignant Thymoma
Keywords: B3 and C malignant thymoma
Lead sponsor: Tiziana Life Sciences LTD
Sponsor class: INDUSTRY
First posted: 2011-02-23
Enrollment: 30
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 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.

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

Primary outcomes:
measure: Progression-free Survival Rate at 3 Months
timeFrame: 3 months since treatment start
Secondary outcomes:
measure: Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters
timeFrame: 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.
measure: Objective Response Rate (ORR)
timeFrame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
measure: Disease Control Rate (ORR+SD Rate)
timeFrame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
measure: Duration of Response
timeFrame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
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: Progression-free Survival (PFS)
timeFrame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks.
Other outcomes:
Locations:
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Bethesda
country: United States
facility: NIH, Center for Cancer Research, Medical Oncology
state: Maryland
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
state: (mi)
Study officials:
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
affiliation: MedStar Gergetown University Hospital
name: Giuseppe Giaccone, MD
role: PRINCIPAL_INVESTIGATOR
References: