| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Anemia in subjects with advanced stage non-small cell lung cancer receiving multi-cycle chemotherapy. |
|
| E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer
Anemia
Cancer
Lung Cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10064469 |
| E.1.2 | Term | Anemia post chemotherapy |
| E.1.2 | System Organ Class | 100000004851 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
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. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Tumour Sample Banking
If available and upon the consent of the subjects, paraffin embedded tumor tissue blocks or unstained tumor slides (from primary tumor or metastasis) will be collected at screening and archived for erythropoietin receptor (EpoR) testing, tumor mutation analysis, and other biomarker evaluation. There will not be an additional procedure required but rather these tumor samples may be obtained from previous diagnostic biopsy. |
|
| E.3 | Principal inclusion criteria |
Disease Related
• Subjects with stage IV NSCLC (not recurrent or re-staged)
• Expected to receive at least 2 additional cycles (at least 6 total weeks) of first line myelosuppressive cyclic chemotherapy after randomization. Subjects should not be expected to receive only maintenance chemotherapy.
Demographic
• Eastern Cooperative Oncology Group performance status of 0 or 1 as assessed within 21 days prior to randomization
• 18 years of age or older at screening.
• Life expectancy > 6 months based on the judgment of the investigator and documented during screening.
Laboratory
• Hemoglobin level ≤ 11.0 g/dL as assessed by the local laboratory;
sample obtained within 7 days prior to randomization (retest in screening is acceptable).
• Adequate serum folate (≥ 2 ng/mL) and vitamin B12 (≥ 200 pg/mL) levels assessed by central laboratory (supplementation and retest acceptable) during screening.
Imaging
• Subjects must have had a baseline scan (CT, MRI, or PET/CT) of the chest to assess disease burden before starting on first line chemotherapy for NSCLC and those images must have been reviewed
by the investigator prior to randomization. If the scan was performed more than 28 days prior to randomization, an additional scan must be performed and reviewed by the investigator to confirm that the patient has not progressed before randomization.
Ethical
• Before any study-specific procedure, the appropriate written informed consent must be obtained from the subject or a legally accepted representative. |
|
| E.4 | Principal 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.
• Received any prior adjuvant or neoadjuvant therapy for NSCLC
• Subjects with a history of brain metastasis.
• Uncontrolled hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg), or as determined by the investigator during 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 randomization.
• Subjects with a history of seizure disorder taking anti-seizure medication within 30 days prior to randomization.
• Clinically significant systemic infection or uncontrolled chronic inflammatory disease (eg, rheumatoid arthritis, inflammatory bowel disease) as determined by the investigator during screening.
• 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 randomization.
Laboratory
• Transferrin saturation < 20% and ferritin < 50 ng/mL as assessed by the
central laboratory during screening. Subjects must have both to be
excluded supplementation and retest acceptable).
• Abnormal renal function (serum creatinine level > 2X ULN) as assessed by
the central laboratory during screening.
• Abnormal liver function (total bilirubin > 2X ULN or liver enzymes ALT or AST > 2.5X ULN for subjects without liver metastasis or ≥ 5X ULN for subjects with liver metastasis) as assessed by the central laboratory during 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 (eg, rHuEPO, darbepoetin alfa).
• ESA therapy within the 28 days prior to randomization.
• 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). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Survival status will be assessed every 3 months ± 2weeks. |
|
| E.5.2 | Secondary end point(s) |
Progression-free survival (PFS)
Incidence of at least 1 RBC transfusion or hemoglobin ≤ 8.0 g/dL from week 5 (day 29) to the end of the efficacy treatment period (EOETP; defined as 21 days after either the last dose of IP or the last dose of chemotherapy, whichever is later; the EOETP will be set to the EOTP if the EOETP exceeds the EOTP) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Assessment of progression-free survival, RBC transfusions and Hb at: screening; Day1/Week; Weeks 4, 7, 10, 13, 16, 19, 22, 25, 28... during the treatment period.; at last dose of IP; and at next Q3W visit after disease progression |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 75 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Canada |
| Chile |
| China |
| Croatia |
| Hong Kong |
| India |
| Israel |
| Mexico |
| Philippines |
| Russian Federation |
| Serbia |
| South Africa |
| Switzerland |
| Taiwan |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Since this is an event driven protocol, this study will end when approximately 2700 deaths have occurred.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
