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A Phase II Trial of Pazopanib, in Relapsed and Refractory Small Cell Lung Cancer (SCLC)

Phase 2
18 Years
Open (Enrolling)

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Trial Information

A Phase II Trial of Pazopanib, in Relapsed and Refractory Small Cell Lung Cancer (SCLC)

Small cell lung cancer is a tumor that initially responds to chemotherapy and radiotherapy,
however, it is associated with very poor prognosis since the initial response is nearly
always followed by relapse and metastasis. The response to subsequent therapy is very
limited as is the duration of response in these patients. Patients with SCLC have high rates
of metastases at presentation suggesting that angiogenesis is particularly important in this
cancer, furthermore studies have shown that microvessel density and VEGF expression in SCLC
tumor samples correlate with development of metastases and poor prognosis. Furthermore VEGF
expression was the only factor that retained a significant inverse correlation with survival
when assessed in a multivariate analysis.

Pazopanib is a potent, small molecule competitive inhibitor of the tyrosine kinase activity
of (VEGFR 1), VEGFR 2, VEGFR 3, platelet derived growth factor (PDGF), and c kit, capable of
inhibiting downstream signalling from these receptors. The IC50 of pazopanib against VEGFR 2
is 10nm, and the IC50 against VEGFR 1 is <50nm. Currently a number of studies is underway
for the evaluation of pazopanib in the treatment NSCLC. Administering pazopanib to patients
with relapsed SCLC offers an attractive choice in patients with very limited therapeutic
choices. The high rate of metastasis highlights the need for alternative treatments that
act directly on the growth and invasion of tumors and subsequent development of metastases,
rather than solely on cell proliferation.

Inclusion Criteria:

- Patients 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 patient'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

- Age ≥ 18 years

- Diagnosis of SCLC based on either histology or cytology (by FNA) with radiologically
confirmed progressive disease after first-line chemotherapy.

- Presence of brain metastases is permitted if patient has completed treatment with
surgery and/or radiation more than four weeks prior to date of first dose of study
drug. Patients who have developed brain metastases following prophylactic cranial
irradiation will not be eligible for participation

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

- Measurable disease criteria according to RECIST 1.1

- Only one prior chemotherapy regimen

- Biologic material (blood samples, archived tissue) will be collected from consenting
patients for biomarker analysis before and/or during treatment with investigational

- Adequate organ system function

- 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

- 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

- Patients 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)

- Patients 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 subject. Double barrier
method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal
spermicidal agent (foam/gel/film/cream/suppository) Female subjects who are lactating
should discontinue nursing prior to the first dose of study drug and should refrain
from nursing throughout the treatment period and for 14 days following the last dose
of study drug

Exclusion Criteria:

- Prior malignancy

- Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors

- 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

- 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

- Presence of uncontrolled infection.

- Corrected QT interval (QTc) > 480 msecs using Bazett's formula

- 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

- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg
or diastolic blood pressure (DBP) of ≥ 90mmHg]

- History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months

- 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)

- Evidence of active bleeding or bleeding diathesis

- 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)

- Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of
study drug

- 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

- 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 to the first dose of study
drug and for the duration of the study

- Treatment with any of the following anti-cancer therapies: radiation therapy, surgery
or tumor embolization within 14 days prior to the first dose of pazopanib or
chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal
therapy within 14 days or five half-lives of a drug (whichever is longer) prior to
the first dose of pazopanib

- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity, except alopecia

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Rate

Outcome Description:

Patients will be assessed every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 168 weeks

Outcome Time Frame:

2 Years

Safety Issue:



Greece: National Organization of Medicines

Study ID:




Start Date:

November 2011

Completion Date:

January 2014

Related Keywords:

  • SCLC
  • SCLC
  • 2nd Line
  • Relapsed or Refractory
  • Lung Neoplasms
  • Small Cell Lung Carcinoma