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Trial record 3 of 4 for:    PHA-848125AC

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

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ClinicalTrials.gov Identifier: NCT01301391
Recruitment Status : Active, not recruiting
First Posted : February 23, 2011
Results First Posted : October 4, 2018
Last Update Posted : October 4, 2018
Sponsor:
Information provided by (Responsible Party):
Tiziana Life Sciences, PLC

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.

Condition or disease Intervention/treatment Phase
Malignant Thymoma Drug: Milciclib Maleate Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study Of Oral PHA-848125AC In Patients With Malignant Thymoma Previously Treated With Multiple Lines Of Chemotherapy
Actual Study Start Date : February 2, 2011
Actual Primary Completion Date : May 31, 2017
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thymus Cancer

Arm Intervention/treatment
Experimental: Milciclib
Milciclib Maleate capsules
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




Primary Outcome Measures :
  1. Progression-free Survival Rate at 3 Months [ Time Frame: 3 months since treatment start ]
    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 :
  1. Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters [ 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. ]

    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.


  2. Objective Response Rate (ORR) [ Time Frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. ]
    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.

  3. Disease Control Rate (ORR+SD Rate) [ Time Frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. ]
    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.

  4. Duration of Response [ Time Frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. ]
    Calculated in patients achieving a confirmed objective tumor response by RECIST version 1.1 criteria.

  5. Overall Survival [ 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. ]
    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.

  6. Progression-free Survival (PFS) [ Time Frame: Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01301391


Locations
United States, District of Columbia
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Maryland
NIH, Center for Cancer Research, Medical Oncology
Bethesda, Maryland, United States, 20892
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milano, (mi), Italy, 20133
Sponsors and Collaborators
Tiziana Life Sciences, PLC
Investigators
Principal Investigator: Arun Rajan, MD. National Cancer Institute (NCI)
Principal Investigator: Marina C. Garassino, MD. Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Principal Investigator: Giuseppe Giaccone, MD MedStar Gergetown University Hospital
  Study Documents (Full-Text)

Documents provided by Tiziana Life Sciences, PLC:
Study Protocol  [PDF] March 9, 2017


Responsible Party: Tiziana Life Sciences, PLC
ClinicalTrials.gov Identifier: NCT01301391     History of Changes
Other Study ID Numbers: CDKO-125a-007
First Posted: February 23, 2011    Key Record Dates
Results First Posted: October 4, 2018
Last Update Posted: October 4, 2018
Last Verified: September 2018

Keywords provided by Tiziana Life Sciences, PLC:
B3 and C malignant thymoma

Additional relevant MeSH terms:
Thymoma
Thymus Neoplasms
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lymphatic Diseases
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action