ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer - Full Text View

Sponsor:	AstraZeneca
Information provided by:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00312377

Purpose

This large phase III clinical study is studying the effect of vandetanib (ZACTIMA) in treating non-small cell lung cancer (NSCLC). Vandetanib is a new type of agent that targets the blood supply to a cancer tumour (through it's anti-VEGFR properties) and the tumour cells themselves (through it's anti-EGFR actions). This study will look at the effects of vandetanib in lung cancer patients who have had their cancer re-appear after treatment with standard chemotherapy.

This clinical study will test if the vandetanib anti-VEGF and anti-EGFR characteristics can deliver longer improved progression free survival and improved overall survival than docetaxel (Taxotere) alone.

All patients participating this clinical study will receive treatment with docetaxel, a commonly used treatment for recurrent non-small cell lung cancer.

In addition, some patients will also receive vandetanib (ZACTIMA), an anti-EGFR / anti-VEGF agent.

Recent clinical research shows that vascular endothelial growth factor receptor (VEGFR) inhibition, when used with standard chemotherapy, can lead to increased survival in advanced non-small cell lung cancer (NSCLC) patients.

Other research shows that epidermal growth factor receptor (EGFR) inhibitors, like erlotinib (Tarceva) can also increase overall non-small cell lung cancer survival by killing tumour cells and stopping them from dividing.

Condition	Intervention	Phase
Non-small Cell Lung Cancer Lung Cancer	Drug: Docetaxel Drug: Vandetanib	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase III, Randomized, Double-Blinded, Multi-Center, Study to Assess the Efficacy of Docetaxel (TAXOTERE™) in Combination With ZD6474 (ZACTIMA™) Versus Docetaxel (TAXOTERE™) With Placebo in Subjects With Locally Advanced or Metastatic NSCLC

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Docetaxel Vandetanib

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Progression-Free Survival (PFS) in the Overall Population [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective disease progression ] [ Designated as safety issue: No ]
Median time (in weeks) from randomisation 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
Progression-Free Survival (PFS) in the Female Population [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective disease progression ] [ Designated as safety issue: No ]
Median time (in weeks) from randomisation 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

Secondary Outcome Measures:

Overall Survival (OS) in the Overall Population [ Time Frame: Time to death in months ] [ Designated as safety issue: No ]
Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
Overall Survival (OS) in the Female Population [ Time Frame: Time to death in months ] [ Designated as safety issue: No ]
Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
Objective Response Rate (ORR) [ Time Frame: Each patient 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 from randomisation until objective progression ] [ Designated as safety issue: No ]
The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR).

Each patient's best objective response will be determined. The categories for best objective response are CR, PR, stable disease (SD)>= 6 weeks, progressive disease (PD) or NE.
Disease Control Rate (DCR) [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression ] [ Designated as safety issue: No ]
Disease control rate is defined as the number of patients who achieved disease control at 6 weeks following randomisation. Disease control at 6 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 6 weeks
Duration of Response (DoR) [ Time Frame: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression ] [ Designated as safety issue: No ]
Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)
Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Lung Cancer Subscale (LCS) [ Time Frame: FACT-L questionnaires are to be administered every 3 weeks after randomisation ] [ Designated as safety issue: No ]
Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days.

A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.
Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI) [ Time Frame: FACT-L questionnaires are to be administered every 3 weeks after randomisation ] [ Designated as safety issue: No ]
Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days.

A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.

Enrollment:	1391
Study Start Date:	May 2006
Estimated Study Completion Date:	December 2011
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Docetaxel monotherapy	Drug: Docetaxel infusion Other Name: TAXOTERE™
Experimental: 2 Vandetanib + Docetaxel	Drug: Docetaxel infusion Other Name: TAXOTERE™ Drug: Vandetanib oral Other Names: ZACTIMA™ ZD6474

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Lung cancer patients who answer true to the following statements are eligible to join this clinical study.

I have a confirmed diagnosis of locally advanced or metastatic non small cell lung cancer (Stage IIIb - IV)
I have had 1st line anti-cancer therapy. Previous treatment with Avastin (bevacizumab) in first line NSCLC is allowed.

Exclusion Criteria:

Lung cancer patients who answer true to the following are NOT eligible to join this clinical study.

I do not have non small cell lung cancer (NSCLC)
I have received treatment with docetaxel (Taxotere). Prior treatment with paclitaxel is acceptable.
I have received 2nd line anti-cancer therapy (For example, patients with previous 2nd line non small cell lung cancer (NSCLC) treatment with Tarceva (erlotinib, OSI-744), Alimta (pemetrexed) are not eligible)
I have been treated with VEGFR-TKIs (sunitinib, sorafenib, other VEGF TKIs). Previous treatment with Avastin (bevacizumab) in 1st line non small cell lung cancer is permitted.
I have a history of uncontrolled irregular heartbeat
I have a history of high blood pressure which has not been controlled with medication

If you are unsure of the meaning of the inclusion and exclusion criteria above, please contact the call center number for help.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312377

Show 167 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:

AstraZeneca Zactima Medical Science Director, MD

AstraZeneca

More Information

Additional Information:

Cancer Study Locator (US and Canada Only) This link exits the ClinicalTrials.gov site

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26.

ClinicalTrials.gov Identifier:	NCT00312377 History of Changes
Other Study ID Numbers:	D4200C00032, 6474IL/0032
Study First Received:	April 6, 2006
Results First Received:	April 27, 2011
Last Updated:	April 27, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Non-small cell lung cancer
NSCLC

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site

Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012