First Line Bio-immunotherapy With Thymosin Alpha 1 in Patients With Sensitizing EGFR Mutation Positive Non Small Cell Lung Cancer Who Are Taking Standard of Care Therapy

Phase I: evaluate the safety and tolerability two different dosing regimens of Thymosin alpha 1 in patients with advanced EGFR mutation positive NSCLC on Standard of Care (SoC) therapy.

Phase II: evaluate the efficacy in terms of PFS of Thymosin alpha 1 in patients with advanced EGFR mutant NSCLC taking SoC as compared to SoC alone.

Study Overview

• Status: Unknown
• Conditions: EGFR Mutation Positive Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Thymalfasin (Thymosin alpha 1, Ta1); Drug: SoC (tyrosine kinase inhibitor)

Detailed Description

Phase I/Phase II, multi-center, open label, randomized, parallel group study to determine the safety/tolerability/efficacy of Thymosin alpha 1 in patients with sensitizing EGFR mutation positive NSCLC taking SoC versus SoC alone. The study will be conducted in subjects with sensitizing EGFR mutation positive Non Small Cell Lung Cancer. Subjects with sensitizing EGFR mutation positive NSCLC will be screened for eligibility by the clinical center involved. The study will be conducted in two parts. In Phase I patients will be randomized to one of two different dosing regimens of Thymosin alpha 1 for a treatment duration of 4 months. At the completion of Phase I, data will be reviewed and a single dosing regimen will be carried forward into Phase II. In Phase II patients will be randomized to SoC or Thymosin alpha 1 plus SoC for treatment duration of 12 months. All patients will be followed for approximately 18 months.

• Study Type: Interventional
• Enrollment (Anticipated): 188
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Carlo Tomino, MD; Email: carlotomino@gmail.com

Study Locations

• Italy
  • Frosinone, Italy
    • Azienda Sanitaria Locale Frosinone
    • Contact: Dott.ssa Teresa Gamucci
    • Principal Investigator: Dott.ssa Teresa Gamucci
  • Milan, Italy
    • Istituto Nazionale dei Tumori
    • Contact: Dott.ssa Marina Chiara Garassino
    • Principal Investigator: Dott.ssa Marina Chiara Garassino
  • Rome, Italy
    • Roma_Campus Bio-Medico
    • Contact: Prof. Daniele Santini
    • Principal Investigator: Prof. Daniele Santini
  • Rome, Italy
    • Sant'Andrea Hospital
    • Contact: Prof. Paolo Marchetti
    • Principal Investigator: Prof. Paolo Marchetti
  • Torino, Italy
    • Presidio Sanitario San Camillo
    • Contact: Dott.ssa Maria Rita Migliorino
    • Principal Investigator: Dott.ssa Maria Rita Migliorino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older
• Histological or cytological confirmation of NSCLC (may be from initial diagnosis of NSCLC or subsequent biopsy). Only patients with available tissue samples may be included in the study (see major details in section 8 for the minimum sample characteristics)
• Activating mutations of EGFRdiagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or metastaticNSCLC, not amenable to curative surgery or radiotherapy
• Measurable disease by Response Evaluation Criteria In Solid Tumours (RECIST) in a lesion not previously irradiated or non-measurable disease (non measurable disease only for Phase I)
• Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-2
• Absolute neutrophil count (ANC) > 1.5 x 109/liter (L) and platelets > 100 x 109/L
• Bilirubin level either normal or <1.5 x ULN
• AST (SGOT) and ALT (SGPT) <2.5 x ULN (≤ 5 x ULN if liver metastases are present)
• Serum creatinine <1.5 x ULN
• Effective contraception for both, male and female patients, if the risk of conception exists
• Provision of written informed consent to the analysis of biological markers (registration)

Exclusion Criteria:

• Prior therapy with Thymosin alpha-1
• Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation.
• Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies
• Radiotherapy within 14 days prior to drug administration, except as follows:
• Palliative radiation to organs other than chest may be allowed up to 2 weeks prior to drug administration, and
• Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
• Patients with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they have evidence of clinically stable disease (SD) (no steroid therapy or steroid dose being tapered) for at least 28 days
• Patients with toxicities that have not coming back (at least) to grade 1
• Pregnancy or suspected pregnancy
• Known severe hypersensitivity to TKI
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
• Any evidence of clinically active interstitial lung disease (ILD) (patients with chronic, stable, radiographic changes who are asymptomatic or patients with uncomplicated progressive lymphangitic carcinomatosis need not be excluded)
• As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
• As judged by the investigator, any inflammatory changes of the surface of the eye
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thymalfasin biw plus SoC (tyrosine kinase inhibitor); Twice weekly thymalfasin	Drug: Thymalfasin (Thymosin alpha 1, Ta1); In Phase I patients will be randomized to one of two different dosing regimens of Thymosin alpha 1 for a treatment duration of 4 months. At the completion of Phase I, data will be reviewed and a single dosing regimen will be carried forward into Phase II.; Other Names: ZADAXIN; Drug: SoC (tyrosine kinase inhibitor); In Phase II patients will be randomized to SoC or Thymosin alpha 1 plus SoC for treatment duration of 12 months. All patients will be followed for approximately 18 months.; Other Names: afatinib, gefitinib, erlotinib
Experimental: Thymalfasin plus SoC (tyrosine kinase inhibitor); 5 times a week thymalfasin	Drug: Thymalfasin (Thymosin alpha 1, Ta1); In Phase I patients will be randomized to one of two different dosing regimens of Thymosin alpha 1 for a treatment duration of 4 months. At the completion of Phase I, data will be reviewed and a single dosing regimen will be carried forward into Phase II.; Other Names: ZADAXIN; Drug: SoC (tyrosine kinase inhibitor); In Phase II patients will be randomized to SoC or Thymosin alpha 1 plus SoC for treatment duration of 12 months. All patients will be followed for approximately 18 months.; Other Names: afatinib, gefitinib, erlotinib
Active Comparator: SoC (tyrosine kinase inhibitor); 12 months	Drug: SoC (tyrosine kinase inhibitor); In Phase II patients will be randomized to SoC or Thymosin alpha 1 plus SoC for treatment duration of 12 months. All patients will be followed for approximately 18 months.; Other Names: afatinib, gefitinib, erlotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of treatment-related adverse events	Up to 4 months
PFS	Up to12 months

Collaborators and Investigators

• Sponsor: SciClone Pharmaceuticals
• Investigators: Principal Investigator: Prof. Paolo Marchetti, MD, S. Andrea Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (Estimate): September 19, 2016

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: September 16, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Non Small Cell Lung Cancer; Thymalfasin; EGFR mutation positive; Thymosin Alpha 1; Tyrosine Kinase inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Adjuvants, Immunologic; Gefitinib; Afatinib; Thymalfasin
• Other Study ID Numbers: SCI-Ta1-NSCLC-P1/2-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided