A Phase 1b/2 study of AMG 655 Combination with Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2006-006658-89-FR
• Date of registration: 14/02/2008
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A Phase 1b/2 study of AMG 655 Combination with Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer
• Scientific title: A Phase 1b/2 study of AMG 655 Combination with Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer
• Date of first enrolment: 28/04/2008
• Target sample size: 165
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006658-89
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, France, Hungary, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Disease Related

• Histologically or cytologically confirmed non-small cell lung cancer. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the subject will be ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy.
• Subjects must have advanced non-small cell lung cancer defined as stage IIIB with
malignant pleural effusion or stage IV or recurrent disease (recurrent disease is defined as documented disease progression following complete surgical resection for stage I or II disease). Subjects with unmeasurable but evaluable disease can be included in the study.
• Planning to receive up to 6 cycles of chemotherapy
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

Demographic

• Men or women = 18 years of age

Ethical

• Before any study specific procedure is performed, the appropriate approved written
informed consent must be obtained

Laboratory

• Hematological function as follows:
- Hemoglobin = 9 g/dL
- Absolute neutrophil count = 1.5 x 109/L
- Platelet count = 100 x 109/L (without a transfusion = 14 days prior to enrollment or randomization)
• Renal function, as follows:
- Calculated creatinine clearance = 40 mL/minute
• Hepatic function, as follows:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 x ULN
OR AST or ALT = 5.0 x ULN if clearly attributable to liver metastasis
- Total bilirubin = 1.5 x ULN
- Alkaline phosphatase = 2.0 x ULN OR alkaline phosphatase = 5 x ULN if liver or bone metastases are present
• Partial thromboplastin (PTT) = 1.0 x ULN and international normalized ratio (INR) = 1.5, unless subject is on anti-coagulation therapy. Subjects on therapeutic anti-coagulation are eligible if there is no bleeding and they are on a stable dose of anticoagulation therapy (eg, warfarin with an INR of 2 to 3) for at least 7 days before
enrollment/randomization.
• Amylase = 2 x ULN
• Lipase = 2 x ULN

General
• Plan to begin protocol specific therapy = 7 days prior to enrollment/randomization
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Disease Related

• Untreated or symptomatic central nervous system metastases. Subjects with a history of brain metastases are eligible if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastasis and the subject is clinically stable and off corticosteroids for at least 14 days before enrollment/randomization.
• Prior chemotherapy as follows:
• Any prior chemotherapy for advanced non-small cell lung cancer
• Any prior adjuvant chemotherapy for non-small cell lung cancer = 52 weeks prior to
enrollment/randomization. Adjuvant chemotherapy completed > 52 weeks prior to
randomization is permitted.
• Any prior chemoradiation.
• Central (chest) radiation therapy = 28 days prior to randomization, radiation therapy for peripheral lesions = 14 days prior to enrollment/randomization
• A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for = 3 years.
• Other abnormal medical conditions
• Documented myocardial infarction or unstable/uncontrolled cardiac condition (eg,
unstable angina, congestive heart failure [New York Heart Association > Class II])
= 52 weeks prior to enrollment/randomization
• History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders = 28 days prior to enrollment/randomization
• History of any medical or psychiatric condition or addictive disorder, or laboratory
abnormality that in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results
• Major surgical procedure = 30 days prior to enrollment/randomization or not yet
recovered from prior major surgery
• Minor surgical procedure = 7 days prior to enrollment/randomization or not yet recovered from prior minor surgery
• Known positive test for human immunodeficiency virus, hepatitis C virus or acute or
chronic hepatitis B infection
• Any co-morbid disease that would increase the risk of toxicity

Medications and other treatments

• Currently treated or previously treated with biologic, small molecule, immunotherapy, or other agents to treat advanced non-small cell lung cancer
• Recent infection requiring a course of systemic anti-infectives that was completed
= 7 days before enrollment/randomization (with the exception of uncomplicated urinary tract infection)
• Yellow fever vaccination within 30 days of randomization

General

• Subject is not able to tolerate intravenous drug infusions
• Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
• Subject of child-bearing potential is evidently pregnant or is breast feeding
• Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men
• Subject has known sensitivity to any of the products to be administered during the study
• Subject was previously enrolled/randomized in this study
• Subject will not be available for follow-up assessment
• Subject has any kind of

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Stage IIIb/IV Non-Small Cell Lung Cancer
MedDRA version: 9.1 Level: LLT Classification code 10029519 Term: Non-small cell lung cancer stage III
MedDRA version: 9.1 Level: LLT Classification code 10029522 Term: Non-small cell lung cancer stage IV

Intervention(s)

Product Name: AMG 655
Product Code: AMG 655
Pharmaceutical Form: Intravenous infusion
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Part 1 (Phase 1b): To determine the maximum tolerated dose up to a
target dose of 15 mg/kg of AMG 655 that can be administered in
combination with paclitaxel/carboplatin

Part 2 (Phase 2): To estimate the efficacy of AMG 655 (at two doses
selected in part 1) in combination with paclitaxel/carboplatin

Secondary Objective: Part 1:
To evaluate the safety and tolerability of escalating doses of AMG 655 in
combination with paclitaxel/carboplatin
To evaluate parameters of clinical benefit as measured by objective
response rate, duration of response, time-to-response, progression-free
survival and overall survival
To evaluate the pharmacokinetics of AMG 655
To evaluate anti-AMG 655 antibody formation

Part 2:
To estimate the clinical benefit of AMG 655 in combination with
paclitaxel/carboplatin as measured by overall objective response rate,
duration of response, time-to-response and overall survival
To evaluate the safety and tolerability of AMG 655 in combination with
paclitaxel/carboplatin
To evaluate the pharmacokinetics of AMG 655 (selected sites)
To evaluate anti-AMG 655 antibody formation

Primary end point(s): Part 1: The incidence of adverse events and clinical laboratory abnormalities defined as dose limiting toxicities

Part 2: Progression free survival

Secondary ID(s)

20060295

2006-006658-89-BE

Ethics review

Status: Approved
Approval date: 28/04/2008
Contact:

Results

• Results available: Yes
• Date Posted: 14/12/2016
• Date Completed: 23/03/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-006658-89/results