Previously Untreated Extensive Stage Small Cell Lung Cancer (SCLC) MedDRA version: 14.0 Level: LLT Classification code 10041067 Term: Small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AMG 479
Product Code: AMG 479
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ganitumab
Current Sponsor code: AMG 479
Concentration unit: mg/ml milligram(
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease related • Histologically or cytologically confirmed SCLC Extensive disease, defined by at least one of the following criteria: - No limited disease (ie, no disease confined to the ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field) - Extrathoracic metastases - Malignant pericardial or pleural effusion - Contralateral hilar adenopathy Measurable or non-measurable disease, as defined by modified RECIST (see Appendix E) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (see Appendix I) Life expectancy (with therapy) = 3 months Demographic Woman or man = 18 years old Ethical Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1) Laboratory Hematological function (within 3 days prior to enrollment), as follows: - Absolute neutrophil count (ANC) = 1.5 x 109/L - Platelet count = 100 x 109/L - Hemoglobin = 9 g/dL Partial thromboplastin time (PTT) = 1.3 x upper limit of normal (ULN) and international normalized ratio (INR) = 1.3 Renal function, as follows: - Creatinine (Cr) clearance (CrCl) = 60 mL/minute (min); calculated by Cockcroft- Gault formula (see Appendix D) as follows: ?????? Male CrCl = (140 - age) x (weight in Kg) / (serum Cr x 72) ?????? Female CrCl = (140 - age) x (weight in Kg) x 0.85 / (serum Cr x 72) Hepatic function, as follows: - Aspartate aminotransferase (AST) = 2.5 x ULN (= 5 x ULN if attributable to liver metastases) - Alanine aminotransferase (ALT) = 2.5 x ULN (= 5 x ULN if attributable to liver metastases) - Alkaline phosphatase = 2.5 x ULN (= 5 x ULN if attributable to bone and/or liver metastases) - Total bilirubin = 1.5 x ULN (= 3 x ULN for subjects with UGT1A1 promoter polymorphism ie, Gilbert syndrome, confirmed by genotyping or Invader UGT1A1 molecular assay prior to enrollment) Fasting blood glucose = 160 mg/dL (Fasting will require subjects to refrain from all food and beverage [except water] for at least 8 hours) Negative pregnancy test (urine or serum) within 7 days prior to enrollment (women of child-bearing potential only) General • Plan to begin protocol specific therapy = 7 days after enrollment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 53
Exclusion criteria
Exclusion criteria: Disease Related Symptomatic or untreated CNS metastasis - Subjects with CNS metastases that are both treated and stably controlled are eligible if all of the following apply: 1. therapy has been administered (surgery and/or radiation therapy); 2. there is no additional treatment planned for brain metastases; 3. the subject is clinically stable; and 4. the subject is off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment Any prior or synchronous malignancy, except: - Malignancy treated with curative intent and with no known active disease present for = 3 years prior to enrollment and felt to be at low risk for recurrence by the treating physician - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease - Adequately treated cervical carcinoma in situ without evidence of disease - Prostatic intraepithelial neoplasia without evidence of prostate cancer Cancer Therapy • Prior chemotherapy, chemo-radiation or investigational agent for the treatment of SCLC - Prior palliative radiotherapy to sites of distant metastasis is allowed (if completed = 7 days prior to enrollment) - Prior treatment of CNS metastasis is allowed (as defined in Section 4.2.1) • Currently or previously treated with biological, immunological or other anti-tumor therapies for SCLC • Prior radiotherapy to > 25% of the bone marrow Medications/Treatments • Recent infection requiring systemic anti-infective treatment that was completed = 14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection) Currently being treated with full dose anti-coagulation therapy (ie coumadin with a goal INR between 2 to 3, or full dose low molecular weight heparin) Medical Conditions History of bleeding diathesis Current serious or non-healing wound or ulcer Known positive test for human immunodeficiency virus, hepatitis C, chronic or active hepatitis B Any clinically significant medical or psychiatric condition, co-morbid disease, addictive disorder, or laboratory abnormality (eg, cardiovascular disease or chronic obstructive pulmonary disease), which may increase the risks associated with study participation or study treatments or could interfere with the safe delivery of study treatment or increase risk of toxicity Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures Major surgical procedure within 28 days prior to enrollment, or not yet recovered from major surgery Minor surgical procedures within 7 days prior to enrollment, or not yet recovered from minor surgery Note: uncomplicated placement of vascular access device = 1 day prior to first administration of study treatment, and fine needle aspiration, thoracocentesis or paracentesis = 3 days prior to first administration of study treatment is acceptable Thrombosis or vascular ischemic events within the last twelve months, such as deep venous thrombosis, pulmonary embolism, transient ischemic attack, cerebral infarction, or myocardial infarction. General Inability to tolerate IV drug administration Subject is currently enrolled in or has not yet completed at least 30 days prior to enrollment since ending other investigational device or clinical study(s) Subject of child-bearing potential is evidently pregnant (eg, positive human chorionic gonadotropin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To identify a dose of AMG 479 in combination with etoposide plus carboplatin and/or etoposide plus cisplatin and of AMG 102 in combination with etoposide plus carboplatin and/or etoposide plus cisplatin that can be administered safely and is tolerated as determined by the incidence of dose-limiting toxicity (DLT) Part 2: To estimate the relative treatment effect of AMG 479 (at the dose selected in Part 1) in combination with chemotherapy (etoposide plus carboplatin and/or etoposide plus cisplatin, as determined in part 1), and of AMG 102 (at the dose selected in Part 1) in combination with chemotherapy, compared with placebo plus chemotherapy, as measured by the respective hazard ratios (HR) for overall survival (OS).;Secondary Objective: Part 1: To evaluate safety as assessed by the incidence of adverse events and laboratory abnormalities not defined as DLT To evaluate safety as assessed by the incidence of anti-AMG 479 antibody formation and anti-AMG 102 antibody formation To evaluate pharmacokinetics (PK) as assessed by the maximum observed serum concentration (Cmax) and the minimum observed serum concentration (Cmin) for AMG 479 and for AMG 102 Part 2: To evaluate clinical benefit as assessed by the objective response rate (ORR) as measured by modified Response Evaluation Criteria in Solid Tumors (RECIST), duration of response (DOR), time to progression (TTP), progression-free survival (PFS), median OS (mOS), and OS rates at 10, 12, 24 and 36 months To evaluate safety as assessed by the incidence of adverse events and laboratory abnormalities For remaining secondary objectives and for exploratory objectives please see the protocol;Primary end point(s): Part 1: ? The incidence of adverse events and clinical laboratory abnormalities defined as DLT Part 2: ? OS;Timepoint(s) of evaluation of this end point: On treatment, 10,12 and 24 months After stopping study treatment, every 3 months for up to 36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 • The incidence of adverse events and laboratory abnormalities not defined as DLT : • The incidence of anti-AMG 479 and anti-AMG 102 antibody formation • PK (Cmax and Cmin for AMG 479 and AMG 102) Part 2 • ORR, DOR, TTP, PFS, mOS, and OS rates at 10,12, 24, and 36 months : • The incidence of adverse events and laboratory abnormalities • The incidence of anti-AMG 479 and anti-AMG 102 antibody formation • PK (Cmax and Cmin) for AMG 479 and AMG 102 • EORTC QLQ-C30 and EORTC QLQ-LC13 scores;Timepoint(s) of evaluation of this end point: 10,12, 24, and 36 months | — |
Countries
Belgium, Czech Republic, France, Hungary, India, Italy, Korea, Republic of, Netherlands, Philippines, Poland, Romania, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactIHQ Medical Information – Clinical
Amgen (EUROPE) GmbH
Outcome results
None listed