A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long-term Safety and Efficacy of Darbepoetin Alfa Administered at 500 µg Once-Every-3-Weeks (Q3W) in Anemic Subjects With Advanced Stage Non-small Cell Lung Cancer Receiving Multi-cycle Chemotherapy.

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2007-005792-34-SI
• Date of registration: 10/02/2010
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long-term Safety and Efficacy of Darbepoetin Alfa Administered at 500 µg Once-Every-3-Weeks (Q3W) in Anemic Subjects With Advanced Stage Non-small Cell Lung Cancer Receiving Multi-cycle Chemotherapy.
• Scientific title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long-term Safety and Efficacy of Darbepoetin Alfa Administered at 500 µg Once-Every-3-Weeks (Q3W) in Anemic Subjects With Advanced Stage Non-small Cell Lung Cancer Receiving Multi-cycle Chemotherapy.
• Date of first enrolment: 21/04/2010
• Target sample size: 3000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005792-34
• 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: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, Germany, Greece, Ireland, Italy, Netherlands, Slovenia, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Disease Related

• Subjects with metastatic (stage IV) or advanced stage IIIB with malignant pleural
effusion NSCLC.

• Receiving or about to receive first line cyclic chemotherapy for NSCLC and expected
to receive at least 2 additional cycles of cyclic chemotherapy.

Demographic

• Eastern Cooperative Oncology Group performance status of 0 or 1 as assessed at
screening.

• 18 years of age or older at screening.

• Life expectancy > 6 months based on the judgment of the investigator and
documented at screening.

Laboratory

• Subjects with chemotherapy-induced anemia as defined as having a hemoglobin
level = 11.0 g/dL at screening. If screening takes more than 7 days, a confirming
hemoglobin level must be performed within 7 days of randomization.

• Subjects must have a pre-chemotherapy hemoglobin value (obtained within 4 weeks prior to starting first line chemotherapy for NSCLC) documented.

• Adequate serum folate (= 2 ng/mL) and vitamin B12 (= 200 pg/mL) levels at screening assessed by central laboratory (supplementation and retest acceptable).

Imaging

• Subjects must have had a baseline scan (chest and upper abdominal CT, MRI, or
PET/CT to assess disease burden before starting on first line chemotherapy for
NSCLC and those images must be available to the investigator.

Ethical

• Before any study-specific procedure, the appropriate written informed consent must
be obtained from the subject or a legally accepted representative.
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

• Known primary benign or malignant hematologic disorder which can cause anemia.

• History of, or current active cancer other than NSCLC, with the exception of
curatively resected non-melanomatous skin cancer, curatively treated cervical
carcinoma in situ, or other primary solid tumors curatively treated with no known
active disease present and no curative treatment administered for the last 3 years.

• Subjects with a history of brain metastasis.

• Uncontrolled hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg), or
as determined by the investigator at screening.

• History of neutralizing antibody activity to rHuEPO or darbepoetin alfa.

• Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator at screening. Subjects with known myocardial
infarction within 6 months prior to screening.

• Subjects with a history of seizure disorder taking anti-seizure medication within 30
days of screening.

• Clinically significant systemic infection or uncontrolled chronic inflammatory disease
(eg, rheumatoid arthritis, inflammatory bowel disease) at the time of screening as
determined by the investigator.

• Known seropositivity for HIV or diagnosis of AIDS, positive for hepatitis B surface
antigen, or seropositive for hepatitis C virus.

• History of pure red cell aplasia.

• History of deep venous thrombosis or embolic event (eg, pulmonary embolism)
within 6 months prior to screening.

Laboratory

• Transferrin saturation < 20% and ferritin < 50 ng/mL at screening. Subjects must
have both to be excluded (supplementation and retest acceptable).

• Abnormal renal function (serum creatinine level > 2 times the upper limit of normal
[ULN]) at screening.

• Abnormal liver function (total bilirubin > 2X ULN or liver enzymes alanine
aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5X ULN for
subjects without liver metastasis or = 5X ULN for subjects with liver metastasis) at
screening. Subjects with documented Gilbert’s Disease may be eligible.

Medications

• Received any RBC transfusion within 28 days prior to randomization.

• Plan to receive any RBC transfusion between randomization and study day 1.

• Known previous treatment failure to ESAs (ie, rHuEPO, darbepoetin alfa).

• ESA therapy within the 28 days prior to screening.

• Known hypersensitivity to recombinant ESAs or the excipients contained within the
investigational product.

General

• Less than 30 days since receipt of any investigational product or device.
Investigational use/receipt of a medicinal product or device that has been approved
by the country’s local regulatory authority for any indication is permitted.

• Subjects of reproductive potential who are pregnant, breast feeding or not willing to use effective contraceptive precautions during the study and for at least one month after the last dose of investigational product in the judgment of the investigator (including females of childbearing potential who are partners of male subjects).

• Previously randomized to this study.

• Investigator has concerns regarding the ability of the subject to give written informed consent and/or to comply with study procedures (including availability for follow-up visits).


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

Health Condition(s) or Problem(s) studied

Anemia in subjects with advanced stage non-small cell lung cancer receiving multi-cycle chemotherapy.
MedDRA version: 9.1 Level: LLT Classification code 10064469 Term: Anemia post chemotherapy

Intervention(s)

Product Name: Darbepoetin alfa 100µg solution for injection
Product Code: Not applicable
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin alfa
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Darbepoetin alfa 200µg solution for injection
Product Code: Not applicable
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin alfa
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Darbepoetin alfa 300µg solution for injection
Product Code: Not applicable
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin alfa
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Name: Darbepoetin alfa 500µg solution for injection
Product Code: Not applicable
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Darbepoetin alfa
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: To demonstrate non-inferiority of progression free survival (PFS) when comparing
subjects on darbepoetin alfa treated to a hemoglobin ceiling of 12.0 g/dL to subjects
treated with placebo.

To demonstrate superiority in reducing the incidence of red blood cell (RBC)
transfusions when comparing subjects on darbepoetin alfa treated to a hemoglobin
ceiling of 12.0 g/dL to subjects treated with placebo.

To assess other safety and efficacy parameters in subjects on darbepoetin alfa
treated to a hemoglobin ceiling of 12.0 g/dL compared to subjects treated with
placebo.

Main Objective: To demonstrate non-inferiority of overall survival (OS) when comparing subjects on
darbepoetin alfa treated to a hemoglobin ceiling of 12.0 g/dL to subjects treated with
placebo.

Primary end point(s): Overall survival

Secondary ID(s)

2007-005792-34-GB

20070782