Clinical trial NCT00738387: A Study of ASA404 or Placebo in Combination With Docetaxel in Second-line Treatment for (Stage IIIb/IV) Non-small Cell Lung Cancer
Official title: A Phase III, Randomized, Double-blind, Placebo-controlled Multi-center Study of ASA404 in Combination With Docetaxel in Second-line Treatment of Patients With Locally Advanced or Metastatic (Stage IIIb/IV) Non-small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Tumor vascular disrupting agent
VDA
ASA404
non-small cell lung cancer
NSCLC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-08-20
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if adding ASA404 to docetaxel chemotherapy makes the cancer treatment more effective in patients with locally advanced or metastatic non-small cell lung cancer


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed non-small cell carcinoma of the lung of all histologies. (Histological or cytological specimens must be collected via surgical biopsy, brushing, washing or core needle aspiration of a defined lesion. Sputum cytology is not acceptable.)
2. Patients who have progressed while on or following a first-line chemotherapy regimen for Stage IIIb disease (malignant pleural effusion or pericardial effusion that have been confirmed cytologically) or Stage IV disease. Patients who have received bevacizumab and/or EGFR inhibitors in first-line will be eligible
3. Age ≥ 18 years old
4. WHO Performance Status of 0-2
5. Not applicable per amendment#2
6. Central laboratory values within the range, as defined below, within 2 weeks of randomization:

   * Absolute neutrophils count (ANC) ≥ 2.0 x 109/L
   * Platelets ≥ 100 x109/L
   * Hemoglobin ≥ 10 g/dL
   * Serum creatinine ≤ 1.5 x ULN
   * Serum bilirubin ≤ 1.5 x ULN
   * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN (≤5 x ULN if liver metastases)
   * International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 x ULN
   * Electrolyte values (sodium, potassium, calcium, magnesium) within ≥1 x LLN and ≤1 x ULN. Patients with corrected electrolyte values are eligible
   * Females of child-bearing potential must have negative serum pregnancy test (confirmation of negative urine pregnancy test within 72 hours prior to initial dosing). Any female presenting with a positive or borderline pregnancy test may undergo a gynecological exam and ultra sound to rule out pregnancy and if found to be negative may be included in the trial.
7. Life expectancy ≥ 12 weeks
8. Written informed consent obtained according to local guidelines

Exclusion Criteria:

1. Patients having CNS metastases (patients having any clinical signs of CNS metastases must have a CT or MRI of the brain performed to rule out CNS metastases in order to be eligible for study participation. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed).
2. Patients with concurrent malignancy, or history or prior malignancy within the past two years, except for basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, treated early stage (T1a) prostate cancer or treated early stage (DCIS or LCIS) breast cancer.
3. Radiotherapy ≤ 2 weeks prior to randomization. Patients must have recovered from all acute radiotherapy-related toxicities.
4. Major surgery must be completed 4 weeks prior to starting study treatment. Major surgery is defined at the investigator's discretion. Insertion of a vascular access device is not considered major or minor surgery. Patients must have recovered from all acute surgery-related complications.
5. Treatment with all prior anticancer therapies ≤ 3 weeks prior to randomization (≤ 6 weeks for bevacizumab, mitomycin and nitrosoureas)
6. Concurrent use of other investigational agents and patients who have received investigational agents ≤ 4 weeks prior to randomization
7. Prior treatment with docetaxel for NSCLC in the locally advanced or metastatic first-line setting
8. Prior treatment with VDAs or tumor - VDAs
9. Any medical condition resulting in ≥ CTC grade 2 dyspnea
10. Patients with systolic BP \> 160 mm Hg and/or diastolic BP \> 90 mm Hg while on medication for hypertension
11. Patients with recent hemoptysis associated with NSCLC (\>1 teaspoon in a single episode within 4 weeks)
12. Patients with any one of the following:

    * Patients with long QT syndrome
    * Patients with a Baseline 12-lead ECG QTcF of \> 450 msec for men or \>470 msec for women using the Fridericia \[QTcF formula\] measurement determined per central ECG evaluation report
    * Congestive heart failure (NY Heart Association class III or IV)
    * Patients with a myocardial infarction within 12 months of starting study treatment or with implanted cardiac pacemaker
    * Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
    * History of poorly-controlled hypertension or poor compliance with anti-hypertensive regimen
    * History of a sustained ventricular tachycardia
    * Presence of atrial tachycardia (e.g., atrial fibrillation, atrial flutter, multifocal atrial tachycardia, supraventricular tachycardia) if not effectively rate-controlled
    * History of ventricular fibrillation or Torsades de Pointes (TdP)
    * Right bundle branch block (RBBB) and either left anterior hemiblock or left posterior hemiblock (bifasicular block)
    * Bradycardia defined as heart rate \<50 beats per minute
    * \[For China only: Patients older than 70 years with evidence of myocardial ischemia by coronary artery angiography or cardiac radionucleotide imaging examination\]
    * \[For China only: Patients with LVEF \<=40%\]
    * Any clinically significant cardiac abnormality as assessed by the investigator
13. Patients who are currently receiving treatment with any medications that have the potential to prolong QT interval or are known to have a risk of causing Torsades de Pointes (See Section 6.8.5.1 and Appendix 2) which cannot be either safely discontinued or switched to a different medication prior to starting study drug administration must be discussed with and approved by the Novartis Global Clinical team prior to randomization.
14. Known allergy or hypersensitivity to docetaxel or drugs formulated with polysorbate 80
15. Peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality)
16. Pregnant or breast feeding females

    • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/ml)
17. Women of child bearing potential or sexually active males, unwilling or unable to use the required highly effective method(s) of contraception for both sexes while receiving treatment and for at least 6 months after the discontinuation of study treatment. (Adequate forms of contraception include IUD, oral or depot contraceptive or the barrier method plus spermicide.)

    • Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions while taking docetaxel and therefore are not considered effective contraceptive methods for this study when used as a single agent. Therefore, it is highly recommended that a concomitant barrier method be used with oral, implantable, or injectable contraceptives. The investigator shall counsel the patient accordingly. Women of childbearing potential must have a negative pregnancy test (serum or urine) 72 hours prior to administration of study treatment. For a list of substrates of human liver microsomal P450 enzymes, visit website (http://medicine.iupui.edu/flockhart/)
18. Concurrent severe and/or uncontrolled medical disease (i.e. uncontrolled diabetes, chronic renal disease, chronic liver disease, confirmed diagnosis of HIV infection or active uncontrolled infection).
19. Significant neurologic or psychiatric disorder which could compromise participation in the study
20. Patient unwilling or unable to comply with the protocol
21. Patients receiving full-dose therapeutic oral or parenteral anticoagulation are ineligible. Patients receiving thrombolytic therapy within 10 days of starting are also ineligible.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Overall survival
timeFrame: Every 6 weeks from study treatment discontinuation until death or loss to follow-up
Secondary outcomes:
measure: Progression free survival
timeFrame: Every 6 weeks from study treatment discontinuation until documented PD, death or loss to follow-up
measure: Overall response rate
timeFrame: Every 42 days (=/- 7 days) from date of randomization until PD
measure: Quality of life
timeFrame: At every odd cycle and at end of treatment
measure: Biomarker assessments
timeFrame: 1 hr post-study drug at cycles 1, 2, 4, 6 and End of Treatment
measure: Pharmacokinetic assessments
timeFrame: 1 hr post-study drug, optional 3-5 hr post-study drug at cycles 1, 2, 3, 4, 5 and 6
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Oncology Specialist, P.c.
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology
state: Arizona
city: Bentonville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare
state: California
city: Highland
country: United States
facility: Beaver Medical Group, L.P.
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: University of Southern Californa
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Northridge
country: United States
facility: North Valley Hematology/Oncology Medical Group
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology/Oncology Specialists
state: California
city: Palo Alto
country: United States
facility: Palo Alto Medical Foundation - Camino Div.
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group
state: California
city: Redlands
country: United States
facility: Loma Linda Oncology Medical Group, Inc.
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Research Institute
state: California
city: San Francisco
country: United States
facility: University of California - SF
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Cancer Centers of Florida, PA
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology/Oncology Associates of Treasure Coast
state: Florida
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology
state: Georgia
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois
state: Illinois
city: Harvey
country: United States
facility: Comprehensive Cancer Program
state: Illinois
city: Niles
country: United States
facility: Cancer Care & Hematology Specialists of Chicagoland
state: Illinois
city: Rockford
country: United States
facility: OSF Center for Cancer Care
state: Illinois
city: Winfield
country: United States
facility: Loyola Cancer Care and Research Center
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Lafayette
country: United States
facility: Horizon Oncology Center
state: Indiana
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates
state: Iowa
city: Overland Park
country: United States
facility: Kansas City Cancer care, Southwest
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Texas
state: Kansas
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Paducah
country: United States
facility: Western Kentucky Hematology & Oncology
state: Kentucky
city: Baltimore
country: United States
facility: Harry & Jeannette Weinberg Cancer Institute
state: Maryland
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Saint Louis
country: United States
facility: St. John's Mercy Medical Center
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Albuquerque
country: United States
facility: New Mexico Cancer Center
state: New Mexico
city: Armonk
country: United States
facility: Advanced Oncology Associates
state: New York
city: Lake Success
country: United States
facility: Arena Oncology Associates, P.C.
state: New York
city: Latham
country: United States
facility: NY Oncology/Hematology - Latham
state: New York
city: Mineola
country: United States
facility: Winthrop Hematology/Oncology
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Cancer Center of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Hematology Oncology Consultants, Inc.
state: Ohio
city: Middletown
country: United States
facility: Signal Point Hematology/Oncology, Inc.
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanante, Northwest Region
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital & Healtth Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Abilene
country: United States
facility: Texas Cancer center - Abilene
state: Texas
city: Arlington
country: United States
facility: Texas Oncology - Arlington South
state: Texas
city: Beaumont
country: United States
facility: Mamie McFadden Ward Cancer Ctr, Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Texas Cancer Center at Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology at Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: Methodist Charlton Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwester Med Ctr at Dallas
state: Texas
city: Denton
country: United States
facility: Texas Cancer Center - Denton
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center
state: Texas
city: Midland
country: United States
facility: Texas Oncology - Allison Cancer Center
state: Texas
city: Paris
country: United States
facility: Paris Regional Cancer Center
state: Texas
city: Sherman
country: United States
facility: Texas Cancer Center - Sherman
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Tyler
country: United States
facility: Blood and Cancer Center of East Texas
state: Texas
city: Waco
country: United States
facility: Texas Oncology Cancer Care Center & Research Center
state: Texas
city: Edmonds
country: United States
facility: Puget Sound Cancer Centers
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Reseach Center
state: Washington
city: Seattle
country: United States
facility: Puget Sound Cancer Center
state: Washington
city: Spokane
country: United States
facility: Evergreen Hematology and Oncology
state: Washington
city: Tacoma
country: United States
facility: MultiCare Health System
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists
state: Washington
city: Antwerpen
country: Belgium
facility: Novartis Investigative Site
city: Arlon
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Namur
country: Belgium
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
city: Greenfield Park
country: Canada
facility: Novartis Investigative Site
city: Laval
country: Canada
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
city: Trois-Rivieres
country: Canada
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
city: Weston
country: Canada
facility: Novartis Investigative Site
city: Winnepeg
country: Canada
facility: Novartis Investigative Site
city: Avignon
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Caen Cedex 5
country: France
facility: Novartis Investigative Site
city: Caen Cedex 9
country: France
facility: Novartis Investigative Site
city: La Chaussée Saint Victor
country: France
facility: Novartis Investigative Site
city: Le mans Cedex
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Nimes
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Perpignan
country: France
facility: Novartis Investigative Site
city: Rennes cedex 5
country: France
facility: Novartis Investigative Site
city: Vandoeuvre-les-Nancy
country: France
facility: Novartis Investigative Site
city: Bamberg
country: Germany
facility: Novartis Investigative site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Coswig
country: Germany
facility: Novartis Investigative Site
city: Eschweiler
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Grosshansdorf
country: Germany
facility: Novartis Investigative Site
city: Guestrow
country: Germany
facility: Novartis Investigative Site
city: Halle
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Hemer
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Deszk
country: Hungary
facility: Novartis Investigative site
city: Gyula
country: Hungary
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
city: Torokbalint
country: Hungary
facility: Novartis Investigative Site
city: Zalaegerszeg-Pozva
country: Hungary
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
city: Aviano
country: Italy
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
city: Cosenza
country: Italy
facility: Novartis Investigative Site
city: Cremona
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Mirano
country: Italy
facility: Novartis Investigative Site
city: Monza
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Palermo
country: Italy
facility: Novartis Investigative Site
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
city: Sassari
country: Italy
facility: Novartis Investigative Site
city: Udine
country: Italy
facility: Novartis InvestigativeSite
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Lonza
country: Poland
facility: Novartis Investigative Site
city: Szczecin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Mataro
country: Spain
facility: Novartis Investigative Site
city: Sabadell
country: Spain
facility: Novartis investigative Site
city: Santander
country: Spain
facility: Novartis Investigative Site
city: Geneve
country: Switzerland
facility: Novartis Investigative Site
city: St. Gallen
country: Switzerland
facility: Novartis Investigative site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: