Efficacy Study Comparing ZD6474 in Combination With Pemetrexed and Pemetrexed Alone in 2nd Line NSCLC Patients

NCT00418886 | Completed Phase 3 Results

• 3 other identifiers: D4200C00036EUDRACT No. 2006-003695-35LPS15296
• Study Type: interventional
• Target: 698
• Locations: 21 countries
• Sites: 110

Brief Summary

Non-small cell lung cancer (NSCLC) can be treated with drugs that kill tumour cells, stop them from dividing, or stop the growth of the blood supply that cancers need to grow and spread. Clinical research has shown that drugs that inhibit vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor (EGFR) signalling can increase overall survival in patients with advanced non-small cell lung cancer (NSCLC). Preclinical studies have shown that vandetanib (ZD6474) is an inhibitor of both VEGFR and EGFR signalling. Giving vandetanib may therefore inhibit the growth of cancer cells by blocking their blood supply and by stopping them from dividing. This lung cancer study is to investigate if adding vandetanib to Alimta (pemetrexed) is more effective than Alimta (pemetrexed) alone.

Conditions

Non Small Cell Lung Cancer; Lung Cancer

Keywords

NSCLC; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS) in the Overall Population

  Median time (in weeks) from randomization until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable Response Evaluation Criteria in Solid Tumors (RECIST) assessment.

  RECIST tumour assessments carried out every 6 weeks (+/- 3 days) from randomization until objective progression

• Progression-Free Survival in the Female Population

  Median time (in weeks) from randomization until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.

  RECIST tumour assessments carried out every 6 weeks (+/- 3 days) from randomization until objective progression

Secondary Outcomes (8)

• Overall Survival (OS)

  Time to death in months

• Objective Response Rate (ORR)

  Each participant was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 6 weeks (+/- 3 days) from randomization until objective progression

• Disease Control Rate (DCR)

  RECIST tumour assessments carried out every 6 weeks (+/- 3 days) from randomization until objective progression

• Duration of Response (DoR)

  RECIST tumour assessments carried out every 6 weeks (+/- 3 days) from randomization until objective progression

• Time to Deterioration of Disease-Related Symptoms (TDS) by Lung Cancer Symptom Scale (LCSS) Total Score

  LCSS questionnaires are to be administered every 3 weeks after randomization

Study Arms (2)

1

PLACEBO COMPARATOR

Placebo Vandetanib + Pemetrexed

Drug: Pemetrexed

2

EXPERIMENTAL

Vandetanib + Pemetrexed

Drug: Vandetanib; Drug: Pemetrexed

Interventions

Vandetanib DRUG

oral once daily tablet

Also known as: ZACTIMA™, ZD6474, SAR390530

2

Pemetrexed DRUG

intravenous infusion

Also known as: Pemetrexed disodium, Alimta®

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent
• Female or male aged 18 years or above
• Histologic or cytologic confirmation of locally advanced or metastatic NSCLC (stage IIIB or IV) on entry into study
• Failure of 1st line anti-cancer therapy (either radiological documentation of disease progression or due to toxicity) or subsequent relapse of disease following 1st line therapy
• WHO Performance status 0 - 2
• 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. Previously irradiated lesions will not be considered measurable.
• Life expectancy of 12 weeks or longer
• Negative pregnancy test for women of childbearing potential only

You may not qualify if:

• Mixed small cell and non-small cell lung cancer histology
• Patients have received 2nd-line or subsequent anti-cancer therapy
• Prior treatment with pemetrexed
• Prior treatment with VEGFR TKIs (previous treatment with bevacizumab \[Avastin\] is permitted)
• Known or suspected brain metastases or spinal cord compression, unless treated at least 4 weeks before entry, and stable without steroid treatment for 10 days
• The last radiation therapy within 4 weeks before the start of study therapy, not including local palliative radiation
• The last dose of prior chemotherapy or other anti-cancer therapy is discontinued less than 3 weeks before the start of study therapy (6 weeks for nitrosoureas, mitomycin, and suramin)
• Major surgery within 4 weeks before entry, or incompletely healed surgical incision
• Neutrophils \<1.5 x 109/L or platelets \<100 x 109/L
• Serum bilirubin \>1.5 x the upper limit of reference range (ULRR)
• Creatinine clearance \<50 ml/min calculated by either Cockcroft -Gault, 24 hours urine collection, EDTA scan or other validated methods
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 x ULRR in the absence of liver metastases, or \> 5 x ULRR in the presence of liver metastases
• Alkaline phosphatase (ALP) \>2.5 x ULRR in the absence of liver metastases, or \>5 x ULRR in the presence of liver metastases
• Current active gastrointestinal disease that may affect the ability of the patient to absorb ZD6474 or tolerate diarrhoea
• 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 study or which would jeopardize compliance with the protocol

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (110)

Research Site

Casa Grande, Arizona, United States

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Chandler, Arizona, United States

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Farmington, Connecticut, United States

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Stamford, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Orlando, Florida, United States

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Gainesville, Georgia, United States

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Skokie, Illinois, United States

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Sioux City, Iowa, United States

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Mount Sterling, Kentucky, United States

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Portland, Maine, United States

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Baltimore, Maryland, United States

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Rockville, Maryland, United States

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Boston, Massachusetts, United States

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St Louis, Missouri, United States

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Mineola, New York, United States

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Rochester, New York, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Middletown, Ohio, United States

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Hilton Head Island, South Carolina, United States

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Austin, Texas, United States

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Salt Lake City, Utah, United States

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Avellaneda, Argentina

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Buenos Aires, Argentina

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Ciudad de Buenos Aires, Argentina

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Córdoba, Argentina

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La Plata, Argentina

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Ramos Mejía, Argentina

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Salta, Argentina

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Santa Fe, Argentina

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Chermside, Australia

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Fitzroy, Australia

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Footscray, Australia

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Heidelberg, Australia

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Randwick, Australia

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St Leonards, Australia

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Wodonga, Australia

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Brussels (Woluwé-St-Lambert), Belgium

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Leuven, Belgium

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Liège, Belgium

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Bogotá, Colombia

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Medellín, Colombia

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Pereira, Colombia

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Valledupar, Colombia

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Avignon, France

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Lyon, France

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Paris, France

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Pontoise, France

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Strasbourg, France

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Cologne, Germany

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Hanover, Germany

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Karlsruhe, Germany

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Kassel, Germany

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Leipzig, Germany

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N. Faliro, Greece

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Pátrai, Greece

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Thessaloniki, Greece

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Hong Kong, Hong Kong

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Ahmedabad, India

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Vellore, India

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Beer-Sheeva, Israel

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Haifa, Israel

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Jerusalem, Israel

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Kfar Saba, Israel

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Petah Tikva, Israel

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Safed, Israel

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Tel Litwinsky, Israel

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Ẕerifin, Israel

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Genova, Italy

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Milan, Italy

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Orbassano, Italy

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Roma, Italy

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S.Andrea Delle Fratte, Italy

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Aguascalientes, Mexico

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México, Mexico

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Puebla City, Mexico

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Cebu City, Philippines

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Manila, Philippines

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Pasay, Philippines

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Quezon City, Philippines

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Lisbon, Portugal

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Santa Maria da Feira, Portugal

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Setúbal, Portugal

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Cape Town, South Africa

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Durban, South Africa

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Johannesburg, South Africa

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Port Elizabeth, South Africa

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Pretoria, South Africa

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A Coruña, Spain

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Lugo, Spain

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Majadahonda, Spain

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Mataró(Barcelona), Spain

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Málaga, Spain

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Ourense, Spain

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Santiago de Compostela(A Coru, Spain

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Vigo(Pontevedra), Spain

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Lund, Sweden

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Sundsvall, Sweden

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Umeå, Sweden

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Uppsala, Sweden

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Västerås, Sweden

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Taipei, Taiwan

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Birmingham, United Kingdom

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Edinburgh, United Kingdom

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Leeds, United Kingdom

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Manchester, United Kingdom

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Wolverhampton, United Kingdom

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Caracas, Venezuela

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Valencia, Venezuela

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Related Publications (2)

• de Boer RH, Arrieta O, Yang CH, Gottfried M, Chan V, Raats J, de Marinis F, Abratt RP, Wolf J, Blackhall FH, Langmuir P, Milenkova T, Read J, Vansteenkiste JF. Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2011 Mar 10;29(8):1067-74. doi: 10.1200/JCO.2010.29.5717. Epub 2011 Jan 31.

  PMID: 21282537 RESULT

• Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer. 2015 Mar 23;15:171. doi: 10.1186/s12885-015-1146-8.

  PMID: 25881079 DERIVED

Related Links

• Related Info
• CSR-D4200C00036.pdf
• Vandetanib\_study\_36\_ZEAL\_CSP\_redacted\_SECURE

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

vandetanib; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2007
• First Posted: January 5, 2007
• Study Start: January 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: February 14, 2023
• Last Updated: December 31, 2024
• Results First Posted: March 26, 2012

Record last verified: 2024-12

Locations

GR (3); DE (5); IL (8); ME (3); BE (3); PT (3); US (23); IT (5); PH (4); ES (8); HK (1); AR (8); FR (5); ZA (5); SE (5); TW (1); VE (2); AU (7); CO (4); GB (5); IN (2)