| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
FIRST LINE TREATMENT IN PATIENTS WITH EXTENSIVE STAGE DISEASE SMALL CELL LUNG CANCER
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10041068 |
| E.1.2 | Term | Small cell lung cancer extensive stage |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare progression free survival in patients receiving figitumumab combined with cisplatin (or carboplatin) and etoposide vs. progression free survival in patients receiving cisplatin (or carboplatin) and etoposide alone as first line treatment for extensive stage disease small cell lung cancer. |
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| E.2.2 | Secondary objectives of the trial |
| Please refer to section 2.1 of the protocol for secondary objectives. |
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| 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 |
Optional exploratory research study is available for pts who would like to participate in it. The title is the same as the main protocol title.
‘A PHASE 2, RANDOMIZED, OPEN LABEL STUDY OF FIGITUMUMAB (CP-751,871) PLUS CISPLATIN (OR CARBOPLATIN) AND ETOPOSIDE, VERSUS CISPLATIN (OR CARBOPLATIN) AND ETOPOSIDE ALONE, AS FIRST LINE TREATMENT IN PATIENTS WITH EXTENSIVE-STAGE DISEASE SMALL CELL LUNG CANCER’ dated 6th July 2009
The primary objective of this additional research component is to collect, store, and use samples to investigate possible associations between genomic and metabonomic variation:
•in relation to response to the study drugs, and
•in relation to characteristics of the disease/condition under study in the associated clinical trial, and related conditions.
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| E.3 | Principal inclusion criteria |
Unless compelling reason, to be agreed between Investigator and Sponsor prior to randomization, patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1.Male or females ≥18 years of age.
2.Histologically confirmed SCLC. Tumor tissue is required preferably from available specimens (section/slides) for additional study purposes. New biopsy not required unless existing sample is not available.
3.Extensive stage disease as defined by any of the following criteria:
•Extrathoracic metastasis;
•Malignant pleural effusion;
•Bilateral or contralateral supraclavicular lymphadenopathy.
4.Measurable disease as defined by RECIST 1.1. Baseline measurements/evaluations must be completed within 28 days prior to randomization. Brain metastasis should not be considered measurable/target lesions.
5.At least one week since last radiotherapy and adequate recovery from major surgery with wound healing completed. Patients must have recovered to NCI CTCAE v4.0≤ Grade 1 from all acute toxicities (excluding any Grade toxicity that is not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the investigator.
6.ECOG performance status 0 or 1.
7.Total IGF-1 >120 ng/mL.
8.Patients must have adequate organ function as determined by the following criteria. These must be determined within 7 days prior to randomization:
a.Absolute neutrophil count (ANC) ≥1.5 x 10 (to the power of 9)/L;
b.White blood cell (WBC) ≥4000 cells/ml;
c.Platelet count ≥100 x 10 (to the power of 9)/L;
d.Hemoglobin ≥8 g/dl;
e.Glycosylated hemoglobin (HgbA1c) <5.7%;
f.Creatinine clearance ≥60ml/min (actual or calculated using the Cockcroft Gault formula using actual body weight, see protocol Section 5.3.3.3);
g.BUN ≤25 mg/dl; or Urea ≤8.9 mmol/L;
h.Serum aspartate aminotransferase (AST; serum glutamate oxalate transferase [SGOT]), serum alanine aminotransferase (ALT; serum glutamate pyruvate transferase [SGPT]), and alkaline phosphatase ≤2.5 x ULN, or ≤5 x ULN if liver abnormalities are due to underlying malignancy;
i.Total bilirubin ≤1.5 x ULN (or ≤3 x ULN in patients with confirmed UGT1A1 promoter polymorphism or Gilbert syndrome).
9.Female patients must not be pregnant or nursing. Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 5 months thereafter (or longer if required by local regulation). All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within the 72 hours prior to starting treatment. Male patients with partners of childbearing potential must be surgically sterile or must agree to use effective contraception while receiving study treatment and for at least 5 months thereafter (or longer if required by local regulation). The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate.
10.Patient must be willing and able to comply with scheduled visits (including follow up visits), treatment plans, laboratory tests, collection of patient reported outcomes and other study procedures.
11.Written, voluntary, signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial before enrollment must be provided. |
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| E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the study:
1.Any prior systemic therapy for SCLC.
2.Investigational therapies (targeted or vaccine) for other than SCLC, unless otherwise agreed by investigators and sponsor, will require an appropriate wash out period before enrollment unless otherwise agreed by investigator and sponsor. Must not be simultaneously enrolled in another therapeutic clinical trial for any condition.
3.Patients with symptomatic central nervous system (CNS) metastases are not permitted.
a.Patients with symptoms suggestive of CNS metastases must undergo radiologic/imaging evaluation at baseline to rule out metastases;
b.Patients with known, asymptomatic CNS lesions are permitted;
c.Patients with stable, treated brain metastasis (eg, whole brain radiation therapy or similar) are eligible provided they are on a tapering dose of corticosteroids (see exclusion criteria 7; or are not on corticosteroid therapy).
4.Medically significant hemoptysis, defined as bright red blood of ½ teaspoon or more within 4 weeks prior to randomization;
5.No other active invasive malignancies (previous malignancies are allowed if occurred ≥3 years prior to randomization or current in situ malignancies such as, in situ carcinoma of the cervix, of the uterus, or basal or squamous cell carcinoma of the skin).
6.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study. This includes but is not limited to:
a.Uncontrolled hypertension, uncontrolled diabetes or insulin dependent diabetes;
b.Any history of unstable angina, myocardial infarction or symptomatic congestive heart failure. The requirement for inotropic support or a serious uncontrolled cardiac arrhythmia (atrial flutter/afibrillation) within the past 3 years;
c.Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HBC) and human immunodeficiency virus (HIV). Serological testing will not be required at baseline for patients who have no symptoms suggestive of infection, but is required for patients who do;
d.Pre existing peripheral neuropathy > CTCAE Grade 2;
e.Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol.
7.No use of any concomitant medication that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results. This includes but is not limited to:
a.Requirement for chronic treatment with systemic corticosteroids at doses higher than physiologic replacement (ie, prednisone equivalent 5 mg/day) or other immunosuppressive therapy during study participation. Previous steroid treatment must be discontinued within 1 week prior to study start. Low dose steroid use for the control of nausea and vomiting will be allowed. The use of corticosteroids for the prophylaxis or treatment of nausea and vomiting, or as chemotherapy pre medication, will be allowed at the discretion of the investigator;
b.Previous or concurrent therapy with any IGF IR inhibitor;
c.Use of growth hormone agonist or antagonist, or aminoglycoside antibiotics (nephrotoxic).
8.Patients may not have known or suspected hypersensitivity to any of the study drugs (etoposide and cisplatin (or carboplatin) and figitumumab), study drug classes (eg, platinum) or excipients (eg, polysorbate 80) in the formulation of study drugs.
9.Patients must not have been admitted to an institution by virtue of an order issued by either the judicial or administrative authorities.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival (PFS) defined as the time from randomization to disease progression or death due to any cause, whichever occurs first. |
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| 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 | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| 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 |
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| E.8.7 | Trial has a data monitoring committee | No |
| 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
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| End of Treatment (EOT) Visit: will be performed approximately 28 days from date of last dose. Follow ups- : Will start upon disease progression or initiation of a subsequent anticancer therapy, and completion of the EOT visit. Monthly visits for the collection of new AEs to continue through 90 days post last treatment day, at which time figitumumab PK and ADA blood samples are collected if possible. Monthly telephone contacts then to continue until death or 12 months from last accrual date. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 13 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 13 |
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