A Study of ASA404 or Placebo in Combination With Docetaxel in Second-line Treatment for (Stage IIIb/IV) Non-small Cell Lung Cancer

Not Recruiting

Trial ID: NCT00738387


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

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)

Stanford Investigator(s)

Heather Wakelee
Heather Wakelee

Winston Chen and Phyllis Huang Professor

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine


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

      - 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

      - 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

      - [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 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


drug: ASA404

drug: docetaxel

drug: Placebo

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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