Zactima in Non Small Cell Lung Cancer (NSCLC) ELderly Patients In Combination With or Versus Gemcitabine (ZELIG)

Phase II, Randomised, Double-blind, Two-arm, Parallel Study of Vandetanib (ZACTIMA™ , ZD6474) Plus Gemcitabine (Gemzar® ) or Gemcitabine Plus Placebo as First Line Treatment of Advanced (Stage IIIB or IV) Non Small Cell Lung Cancer (NSCLC) Elderly Patients.

The primary objective of this study is to demonstrate an improvement in Progression-Free Survival (PFS) for the combination of vandetanib plus gemcitabine compared with gemcitabine plus placebo in chemonaïve (not including an adjuvant regimen) patients aged ≥ 70 years with advanced NSCLC.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: ZD6474, Vandetanib; Drug: Gemcitabine; Drug: Placebo to Match ZD6474, Vandetanib

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Padova, Italy
    • Research Site
  • Roma, Italy
    • Research Site
  • (fc)
    • Meldola, (fc), Italy
      • Research Site
  • AV
    • Avellino, AV, Italy
      • Research Site
  • BA
    • Bari, BA, Italy
      • Research Site
  • BG
    • Treviglio, BG, Italy
      • Research Site
  • BO
    • Bologna, BO, Italy
      • Research Site
  • GE
    • Genova, GE, Italy
      • Research Site
  • ME
    • Taormina, ME, Italy
      • Research Site
  • MI
    • Milano, MI, Italy
      • Research Site
  • PG
    • Perugia, PG, Italy
      • Research Site
  • RA
    • Ravenna, RA, Italy
      • Research Site
  • TN
    • Trento, TN, Italy
      • Research Site
  • TO
    • Orbassano, TO, Italy
      • Research Site
  • UD
    • Udine, UD, Italy
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologic or cytologic confirmation of advanced NSCLC (stage IIIB with supraclavicular lymph node metastases or pleural effusion or stage IV) on entry into study
• One or more measurable lesions at least 10 mm in the longest diameter (LD) by spiral CT scan or 20 mm with conventional techniques according to RECIST criteria
• Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted).
• Female or male aged 70 years or above

Exclusion Criteria:

• Patients must not have received prior anti-cancer therapy except in the adjuvant setting
• Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial
• Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of
• History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1.Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with vandetanib alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Drug: ZD6474, Vandetanib; 100 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Zactima; Drug: Gemcitabine; administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle UP to 6 cycles or UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Gemzar
Placebo Comparator: B; Gemcitabine administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1.Patients will receive gemcitabine for up to a maximum of 6 cycles, after which period patients should continue on daily oral dosing with placebo alone until progression. Once a patient has met the study criteria for disease progression on vandetanib/gemcitabine or placebo/gemcitabine, randomised treatment must be permanently discontinued.	Drug: Gemcitabine; administered intravenously at 1200 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle UP to 6 cycles or UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Gemzar; Drug: Placebo to Match ZD6474, Vandetanib; 100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first; Other Names: Zactima

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	Oct 2008- dec 2011

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		Oct 2008- dec 2011
Overall Objective Response		Oct 2008- dec 2011
Duration of Response		Oct 2008- dec 2011
The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine	The Safety and Tolerability Profile of ZD6474 (Vandetanib) in Combination With Gemcitabine is defined as the number of Adverse Events which includes any symptoms and/or Clinically Significant Laboratory or Vital Signs Abnormalities, and/or ECGs Changes	Oct 2008- Dec 2011

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• Gridelli C. Treatment of advanced non small-cell lung cancer in the elderly: from best supportive care to the combination of platin-based chemotherapy and targeted therapies. J Clin Oncol. 2008 Jan 1;26(1):13-5. doi: 10.1200/JCO.2007.14.1820. No abstract available.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: September 15, 2008
• First Submitted That Met QC Criteria: September 15, 2008
• First Posted (Estimate): September 16, 2008

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: August 30, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: NSCLC; ZD6474; LUNG CANCER; GEMCITABINE; PHASE II; ZACTIMA; VANDETANIB; ADVANCED; ELDERLY PATIENTS; RANDOMIZED; DOUBLE-BLIND; histologically or cytologically-confirmed advanced (stage IIIB with supraclavicular lymph node metastases or pleural effusion or stage IV) NSCLC
• 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; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: D4200L00012; EUDRACT n° 2007-004521-22