Clinical trial NCT00991796: CS-1008 With Carboplatin/Paclitaxel in Chemotherapy naïve Subjects With Metastatic or Unresectable Non-small Cell Lung Cancer (NSCLC)
Official title: Randomised, Double-Blinded, Placebo Controlled, Phase 2 Study of CS-1008 in Combination With Carboplatin/Paclitaxel in Chemotherapy naïve Subjects With Metastatic or Unresectable Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2009-10-08
Enrollment: 109
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 the effect on toxicity of the addition of CS 1008 to a platinum based chemotherapy regimen on the progression-free survival (PFS) in subjects with stage IIIB wet or stage IV NSCLC.


Eligibility criteria: Inclusion Criteria:

* At least 18 years of age.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Measurable disease as defined by RECIST criteria
* Adequate organ and bone marrow function as evidenced by:

  * Hemoglobin \>= 9 g/dL;
  * ANC \>= 1.5 x 109/L;
  * Platelet count \>= 100 x 109/L;
  * Serum creatinine \< 1.5 mg/dL or creatinine clearance \> 60 mL/min;
  * AST, ALT, and alkaline phosphatase \<= 2.5 x upper limit of normal (ULN) if without liver metastasis and \<= 5.0 x ULN if liver metastasis;
  * Total bilirubin \<= 2.0 x ULN.
* Men and women of childbearing potential must be willing to consent to using effective double barrier contraception (eg, hormonal contraceptives, bilateral tubal ligation, barrier with spermicidal, intrauterine device) while on treatment and for 3 months thereafter.
* All female subjects of childbearing potential must have a negative pregnancy test (serum or urine) result \<= 72 hours before initiating study treatment.
* Subjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IEC approved ICF before performance of any study specific procedures or tests.

Exclusion Criteria:

* Anticipation of need for a major surgical procedure or radiotherapy (RT) during the study.
* Prior treatment with chemotherapy for their disease.
* History of any of the following conditions within 6 months before study enrolment: myocardial infarction; New York Heart Association (NYHA) class II or higher severe/unstable angina pectoris; coronary/peripheral artery bypass graft; NYHA class III or IV congestive heart failure; cerebrovascular accident or transient ischemic attack, pulmonary embolism, or other clinically significant thromboembolic event; clinically significant pulmonary disease (eg, severe chronic obstructive pulmonary disease or asthma); clinically significant pulmonary edema or anasarca.. See Section 17.2 for NYHA Classification.
* Clinically significant pleural or pericardial effusions.
* Grade 2 or higher current peripheral neuropathy (See Section 17.3; NCI CTCAE, Version 3.0).
* Clinically active brain metastasis (ie, untreated, still requiring therapy with steroids or RT, or with progression within 4 weeks after completion of RT); an uncontrolled seizure disorder; spinal cord compression; or carcinomatous meningitis.
* History of malignancy other than NSCLC, unless there is the expectation that the malignancy has been cured, and tumor specific treatment for the malignancy has not been administered within the previous 5 years.
* Clinically significant active infection that requires antibiotic therapy or Human Immunodeficiency Virus (HIV) positive subjects receiving antiretroviral therapy.
* Previous treatment with chemotherapy, CS 1008, other agonistic DR 5 or DR 4 antibodies, or with TRAIL.
* Pregnant or breast feeding.
* Known history of hypersensitivity reactions to any of the components of CS 1008, carboplatin, or paclitaxel formulations.
* Serious intercurrent medical or psychiatric illnesses or any other conditions that in the opinion of the Investigator would impair the ability to give informed consent or unacceptably reduce protocol compliance or safety of the study treatment.

Primary outcomes:
measure: Difference in progression-free survival (PFS) of patients treated with CS-1008 and paclitaxel/carboplatin versus placebo and paclitaxel/carboplatin
timeFrame: 6 months
Secondary outcomes:
measure: Difference in overall survival of patients treated with CS-1008 and paclitaxel/carboplatin versus placebo and paclitaxel/carboplatin
timeFrame: 1 year
measure: Difference in objective response rate (ORR) of patients treated with CS-1008 and paclitaxel/carboplatin versus placebo and paclitaxel/carboplatin
timeFrame: 1 year
measure: Difference in duration of response of patients treated with CS-1008 and paclitaxel/carboplatin versus placebo and paclitaxel/carboplatin
timeFrame: 1 year
Other outcomes:
Locations:
city: Gauting
country: Germany
facility: Asklepios Fachkliniken Munchen Gauting
city: Grobhansdorf
country: Germany
facility: Zentrum fur Pneumologie und Thoraxchirurgie
Study officials:
References:
citation: Reck M, Krzakowski M, Chmielowska E, Sebastian M, Hadler D, Fox T, Wang Q, Greenberg J, Beckman RA, von Pawel J. A randomized, double-blind, placebo-controlled phase 2 study of tigatuzumab (CS-1008) in combination with carboplatin/paclitaxel in patients with chemotherapy-naive metastatic/unresectable non-small cell lung cancer. Lung Cancer. 2013 Dec;82(3):441-8. doi: 10.1016/j.lungcan.2013.09.014. Epub 2013 Oct 1.