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

• ClinicalTrials.gov Identifier: NCT01011439
• Recruitment Status: Terminated
• First Posted: November 11, 2009
• Results First Posted: October 16, 2018
• Last Update Posted: February 6, 2019
• Sponsor: Tiziana Life Sciences, PLC
• Information provided by (Responsible Party): Tiziana Life Sciences, PLC

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.

Condition or disease	Intervention/treatment	Phase
Thymic Carcinoma	Drug: Milciclib Maleate	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma Previously Treated With Chemotherapy
• Actual Study Start Date: February 22, 2010
• Actual Primary Completion Date: May 31, 2017
• Actual Study Completion Date: December 17, 2018

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

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. Confirmed Objective Response Rate (ORR) [ Time Frame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD. ]
   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.
2. Disease Control Rate [ Time Frame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD. ]
   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.
3. Progression-free Survival [ Time Frame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD. ]
   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.
4. Duration of Response [ Time Frame: Assessments were made every 6 weeks from start date until PD to a maximum duration of 242 weeks or until PD. ]
   Assessed 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 the start of treatment for a disease, such as cancer, to the date in which the patients diagnosed with the disease were still alive.
6. Overall Safety Profile (Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters) [ 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. ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• 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

  Study Documents (Full-Text)

Documents provided by Tiziana Life Sciences, PLC:

Study Protocol  [PDF] March 9, 2017

Statistical Analysis Plan: CDKO-125a-006_ALG_V1  [PDF] July 8, 2013

Statistical Analysis Plan: CDKO-125a-006_TLG_V1  [PDF] July 8, 2013

More Information

• Responsible Party: Tiziana Life Sciences, PLC
• ClinicalTrials.gov Identifier: NCT01011439
• Other Study ID Numbers: CDKO-125a-006; 2009-014338-79 ( EudraCT Number )
• First Posted: November 11, 2009
• Results First Posted: October 16, 2018
• Last Update Posted: February 6, 2019
• Last Verified: January 2019

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