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Phase 1

• Conditions: Relapsed and Refractory Small Cell Lung Cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000879-14-GR
• Lead Sponsor: Hellenic Oncology Research Group (H.O.R.G.)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05-17
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up.
Procedures conducted as part of the subject’s routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
2. Age = 18 years or legal age of consent if greater than 18 years
3. Diagnosis of SCLC based on either histology or cytology (by FNA) with radiologically confirmed progressive disease after first-line chemotherapy.
4. Presence of brain metastases is permitted if subject has completed treatment with surgery and/or radiation more than four weeks prior to date of first dose of study drug. Subjects who have developed brain metastases following prophylactic cranial irradiation will not be eligible for participation.
5. Eastern Cooperative Oncology Group (ECOG) performance status of = 2.
6. Measurable disease criteria according to RECIST 1.1
7. Only one prior chemotherapy regimen
8. Biologic material (blood samples, archived tissue) will be collected from consenting patients for biomarker analysis before and/or during treatment with investigational product.
9. Adequate organ system function
10. Localised irradiation for SCLC is permitted as long as it was a minimum of 4 weeks before entering the study; however, single-dose palliative radiation of bone metastases for pain control may be allowed during the 4-week screening period.
11. A female is eligible to enter and participate in this study if she is of:
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:
•A hysterectomy
•A bilateral oophorectomy (ovariectomy)
•A bilateral tubal ligation
•Is post-menopausal

Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for = 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).
Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT
Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
•Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product
•Oral contraceptive, either combined or progestogen alone
•Injectable progestogen
•Implants of levonorgestre
•Estrogenic vaginal ring
•Percutaneous contraceptive patches
•Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year
•Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that

Exclusion Criteria

1. Prior malignancy.
2. Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors.
3. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
•Active peptic ulcer disease
•Known intraluminal metastatic lesion/s with risk of bleeding
•Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn’s disease), or other gastrointestinal conditions with increased risk of perforation
•History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
4.Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
•Malabsorption syndrome
•Major resection of the stomach or small bowel.
5. Presence of uncontrolled infection.
6. Corrected QT interval (QTc) > 480 msecs using Bazett’s formula
7. History of any one or more of the following cardiovascular conditions within the past 6 months:
•Cardiac angioplasty or stenting
•Myocardial infarction
•Unstable angina
•Coronary artery bypass graft surgery
•Symptomatic peripheral vascular disease
•Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
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8. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study
9. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
11. Evidence of active bleeding or bleeding diathesis.
12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary haemorrhage, for example:
•Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed
•Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed
•Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, tumour touching but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).
13. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.
14. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject’s safety, provision of informed consent, or compliance to study procedures.
15. Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified