Last updated: 11/03/2018 19:31:19
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

A Phase II Study of Pazopanib GW786034, NSC# 737754 in Children, Adolescents and Young Adults with Refractory Solid Tumors

GSK study ID
116731
Clinicaltrials.gov ID
NCT01956669
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase II Study of Pazopanib GW786034, NSC# 737754 in Children, Adolescents and Young Adults with Refractory Solid Tumors
Trial description: The purpose of this study is to find out what effects, good or bad, pazopanib (GW786034), National Service Center (NSC) # 737754, has on children, adolescents and young adults between 12 months and less than or equal to 18 years of age with relapsed or refractory rhabdomyosarcoma, non rhabdomyosarcomatous soft tissue sarcoma, Ewing sarcoma, relapsed or refractory osteosarcoma, neuroblastoma (measurable and/or evaluable), or hepatoblastoma. This is a two-stage open label phase II trial of pazopanib in children, adolescents and young adults with recurrent or refractory solid tumors. Eligible subjects will receive pazopanib daily as an oral tablet (450 mg/m^2/dose) or as a powder for suspension (225 mg/m^2/dose) in 28 day cycles. The maximum dose to be administered daily for tablets is 800 mg and for suspension 400 mg. Subjects will be closely monitored with clinical and laboratory observations for side effects. Response to treatment will be evaluated using appropriate imaging studies. In the absence of severe toxicity or
progressive disease, subjects may continue receiving pazopanib.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
N\A
Primary outcomes:

The investigator assessed objective response rate (ORR) in subjects’ with tumors of primary interest

Timeframe: Up to 24 cycles from the start of treatment

Secondary outcomes:

The investigator assessed ORR for the tumor types of secondary interest.

Timeframe: Up to 2 years from the start of treatment

Progression free survival (PFS) as assessed by the Investigator in subjects with relapsed or refractory solid tumors

Timeframe: Upto 2 years from the start of treatment

The time to progression (TTP) in subjects with relapsed or refractory solid tumors

Timeframe: Upto 2 years from the start of treatment

Pazopanib pharmacokinetic/pharmacodynamic relationships with biomarkers and clinical outcomes

Timeframe: Upto 2 years from the start of treatment

The therapeutic activity (a confirmed complete or partial response or stable disease for at least 4 cycles) per stratum

Timeframe: Upto 2 years from the start of treatment

Incidence of toxicities of oral pazopanib

Timeframe: Upto 2 years from the start of treatment

Composite of pharmacokinetic (PK) parameters of pazopanib after administration of the oral suspension

Timeframe: Upto 2 years from the start of treatment

The relationship between tumor response and angiogenic cytokines.

Timeframe: Upto 2 years from the start of treatment

Vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR) genotype/phenotype relationships in subjects with cancer treated with pazopanib.

Timeframe: Upto 2 years from the start of treatment

Interventions:
  • Drug: Pazopanib GW786034
    • Enrollment:
    154
    Primary completion date:
    Not applicable
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Solid Tumours
    Product
    pazopanib
    Collaborators
    Children’s Oncology Group
    Study date(s)
    October 2014 to August 2019
    Type
    Interventional
    Phase
    1/2

    Participation criteria

    Sex
    Female & Male
    Age
    1 - 18 Year
    Accepts healthy volunteers
    none
    • Subjects must be at least 1 and less than or equal to 18 years of age at the time of study entry.
    • Subjects must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse - a) Rhabdomyosarcoma, b) Non-rhabdomyosarcomatous Soft Tissue Sarcoma (including desmoplastic small round cell tumor), c) Ewing Sarcoma / Peripheral Primitive Neuroectodermal Tumor (PNET), d) Osteosarcoma, e) Neuroblastoma (Measurable), f) Neuroblastoma (Evaluable), g) Hepatoblastoma. Note: Investigators are encouraged to enroll hepatoblastoma subjects on the appropriate COG biology study (eg: ABTR01B1) if they haven’t already been enrolled and send available relapse tumor and/or blood samples in order to allow for future correlative biology studies in these subjects.
    • Pregnant or breast-feeding women are not eligible for this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Negative pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of the informed consent until at least 30 days after the last dose of the study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate. Study drug may also potentially be secreted in milk and therefore breastfeeding women are excluded.
    • Subjects requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subjects must be at least 1 and less than or equal to 18 years of age at the time of study entry.
    • Subjects must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse
    • a) Rhabdomyosarcoma, b) Non-rhabdomyosarcomatous Soft Tissue Sarcoma (including desmoplastic small round cell tumor), c) Ewing Sarcoma / Peripheral Primitive Neuroectodermal Tumor (PNET), d) Osteosarcoma, e) Neuroblastoma (Measurable), f) Neuroblastoma (Evaluable), g) Hepatoblastoma. Note: Investigators are encouraged to enroll hepatoblastoma subjects on the appropriate COG biology study (eg: ABTR01B1) if they haven’t already been enrolled and send available relapse tumor and/or blood samples in order to allow for future correlative biology studies in these subjects.
    • Subjects who will be receiving the tablet formulation must have a body surface area (BSA) >= 0.84 m^2 (square meter) at the time of study enrollment.
    • Subjects must have radiographically measurable disease (with the exception of neuroblastoma), Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm).
    • Subjects with neuroblastoma who do not have measurable disease but have iodine-131 – meta-iodobenzylguanidine positive (MIBG+) evaluable disease are eligible.
    • Subjects must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2. Use Karnofsky for subjects >= 16 years of age and Lansky for subjects <= 16 years of age.
    • Subjects must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
    • Subjects must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
    • At least 7 days must have elapsed since the completion of therapy with a growth factor that supports platelet or white cell number or function. At least 14 days must have elapsed after receiving peg-filgrastim.
    • At least 7 days must have elapsed since the completion of therapy with a biologic agent. For biologic agents that have known adverse events occurring beyond 7 days after administration, the period prior to enrollment must be extended beyond the time during which adverse events are known to occur.
    • Subjects may have received bevacizumab, VEGF-Trap, or other VEGF blocking tyrosine kinase inhibitors, provided that they did not progress while receiving one of these agents. Subjects may not have previously received pazopanib.
    • At least 21 days must have elapsed since the completion of the last dose of VEGF-Trap, and at least 7 days since a VEGF blocking tyrosine kinase inhibitor. Subjects must have recovered from any VEGF blocking drug-related toxicity (e.g., proteinuria).
    • At least 3 half-lives of the antibody must have elapsed since prior therapy that included a monoclonal antibody.
    • Radiotherapy: >=2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); >=3 months must have elapsed if prior Traumatic Brain Injury (TBI), craniospinal XRT or if >=50% radiation of pelvis; >=6 weeks must have elapsed if other substantial bone marrow irradiation was given.
    • No evidence of active graft versus host disease and >=2 months must have elapsed since transplant or rescue
    • Adequate Bone Marrow Function defined as peripheral absolute neutrophil count (ANC) >=1000/ microlitre (µL), platelet count >= 75,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment); and hemoglobin >= 8.0 grams (g)/decilitre (dL), may receive red blood cell (RBC) transfusions. Subjects with bone marrow involvement will be eligible for study (provided they meet the criteria) but will not be evaluable for hematologic toxicity.
    • Adequate Renal and Metabolic Function defined as creatinine clearance or radioisotope Glomerular filtration rate (GFR) >= 70 millilitre (mL)/ (min)/1.73 meter (m)^2 or A serum creatinine based on age/gender as follows, age 1 to < 2 years (male-0.6 milligrams (mg)/dL, female-0.6 mg/dL), age 2 to < 6 years (male-0.8 mg/dL, female-0.8 mg/dL), age 6 to < 10 years (male-1 mg/dL, female-1 mg/dL), age 10 to < 13 years (male-1.2 mg/dL, female-1.2 mg/dL), age 13 to < 16 years (male-1.5 mg/dL, female-1.4 mg/dL), age >= 16 years (male-1.7 mg/dL, female-1.4 mg/dL), urine creatinine ratio of <1 or a urinalysis that is negative for protein; or, 24-hour urine protein level < 1000 mg/dL, no more than Grade 1 abnormalities of potassium, calcium (confirmed by ionized calcium), magnesium and phosphorous.
    • Adequate Liver Function defined as total bilirubin <=1.5 x upper limit of normal (ULN) for age, serum glutamic-pyruvic transaminase (SGPT) Alanine transaminase (ALT) <=2.5 x ULN (for the purpose of this study, the ULN for SGPT is 45 U/L), Serum albumin >=2 g/dL. Must not have active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment). NOTE: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. No known positivity of hepatitis B surface antigen (HBsAg), or of positive hepatitis C antibody.
    • Adequate Cardiac Function defined as shortening fraction of >=27% by echocardiogram (while not receiving medications for cardiac function), or ejection fraction of >= 50% by gated radionuclide study (while not receiving medications for cardiac function), the corrected QTc interval by Bazett's formula (QTcB) <450 milliseconds (msec), and must not have a history of myocardial infarction, severe or unstable angina, peripheral vascular disease or familial QTc prolongation.
    • Adequate Blood Pressure Control defined as a blood pressure (BP) <= the 95th percentile for age, height, and gender measured, subjects on stable doses of no more than one anti-hypertensive medication, with a baseline BP <= 95th percentile for age, height and gender, will be eligible.
    • Central Nervous System (CNS) Function defined as subjects with a known history of seizures must have well-controlled seizures and may not be receiving enzyme-inducing anti-convulsants, CNS toxicity <= Grade 2.
    • Adequate Coagulation defined as prothrombin time (PT) and partial thromboplastin time (PTT) <= 1.2 x upper limit of normal and an international normalized ratio (INR) <= 1.2.
    Exclusion criteria:
    • Pregnant or breast-feeding women are not eligible for this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Negative pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of the informed consent until at least 30 days after the last dose of the study drug. The definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate. Study drug may also potentially be secreted in milk and therefore breastfeeding women are excluded.
    • Subjects requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible.
    • Subjects who are currently receiving another investigational drug are not eligible.
    • Subjects who are currently receiving other anti-cancer agents or radiation therapy are not eligible.
    • Subjects who are currently receiving more than one anti-hypertensive medication (Grade 3) or whose blood pressure is not well controlled are not eligible for study enrollment.
    • Subjects must not be on therapeutic anticoagulation (Warfarin [coumadin] and/or low molecular weight heparin are prohibited). Prophylactic anticoagulation (i.e. intraluminal heparin) of venous or arterial access devices is allowed.
    • Subjects currently receiving aspirin, and/or ibuprofen, or other Nonsteroidal anti-inflammatory drugs (NSAIDs) are not eligible.
    • Subjects receiving drugs with a known risk of torsades de pointes are not eligible.
    • Subjects who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 4 weeks prior to study enrollment.
    • Subjects who are unable to swallow tablets or liquid are not eligible.
    • Subjects who have an uncontrolled infection are not eligible.
    • Subjects will be excluded if any of the following are present, evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis; History (within 6 months prior to study enrollment) of arterial thromboembolic events, including transient ischemic attack (TIA) or cerebrovascular accident (CVA); history (within 6 months prior to study enrollment) of pulmonary embolism, deep venous thrombosis (DVT), or other venous thromboembolic event; history of hemoptysis within 6 weeks prior to study enrollment.
    • Subjects with known involvement of the CNS by malignancy will be excluded.
    • Subjects who have had or are planning to have the following invasive procedures will be excluded- Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy (Subcutaneous port placement or central line placement is not considered major surgery but must be placed greater than 48 hours from planned Day 1 of therapy); Core biopsy within 7 days prior to Day 1 therapy; Fine needle aspirate or central line placement within 48 hours prior to Day 1therapy.
    • Subjects with serious or non-healing wound, ulcer, or bone fracture.
    • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study enrollment.
    • Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    No study documents available.

    Results overview

    Study Results yet to be posted

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    Not applicable
    Actual study completion date
    Not applicable

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
    Participate in clinical trial
    Access to clinical trial data by researchers
    Visit website