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Refractory or Recurrent Solid Tumors, Excluding CNS TumorsPhase 1NCT02164838

VEGF Receptor Tyrosine Kinase Inhibitor Axitinib in Children With Recurrent or Refractory Solid Tumors

A Phase 1 study testing Axitinib in people with Refractory or Recurrent Solid Tumors, Excluding CNS Tumors, run by Children's Oncology Group at 21 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This trial will be the first study of axitinib in children and adolescents. The primary objective of this Phase 1 trial is to determine a maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of axitinib in pediatric patients with refractory solid tumors. Read more about this study

Who is it for?
Ages 12 months to 17 years
What is being tested?
Axitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
21 sitesin 2 countries
Study dates
Sep 2014to 19 Oct 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 months to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Age: Patients must be > than 12 months and < 18 years of age at the time of study enrollment.
  • Body Surface Area: Patients must have a BSA of ≥ 0.53 m2 at the time of study enrollment.
  • Diagnosis: Patients with refractory or recurrent solid tumors (excluding CNS tumors) and patients with unresectable translocation positive renal cell carcinoma (tRCC) are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse.
  • The diagnosis of translocation morphology or TFE renal cell carcinoma is established by having characteristic morphology AND either a) strong nuclear TFE3 or TFEb staining on immunohistochemistry OR b) cytogenetic studies of the tumor demonstrating a TFE translocation OR c) fluorescent in situ hybridization (FISH) demonstrating a TFE translocation.
  • Disease Status: Patients must have either measurable or evaluable disease
  • Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
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  • Performance Level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age . Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Prior Therapy
  • Patients may have received bevacizumab, VEGF-Trap, or other VEGF blocking tyrosine kinase inhibitors, but may not have received axitinib.
  • Patients must have recovered from any VEGF blocking drug-related toxicity (e.g., proteinuria, hypertension).
  • All patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy.
  • Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
  • Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
  • Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
  • Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
  • Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
  • XRT: At least 14 days after local palliative XRT (small port); At least 150 days must have elapsed if prior TBI, craniospinal XRT or if ≥ 50% radiation of pelvis; At least 42 days must have elapsed if other substantial BM radiation.
  • Stem Cell Infusion without TBI: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion.
  • Organ Function Requirements
  • Adequate Bone Marrow Function Defined As:
  • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3
  • Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Adequate Renal Function Defined As:
  • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or
  • Adequate Liver Function Defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) ≤ 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
  • SGOT (AST) ≤ 125 U/L. For the purpose of this study, the ULN for SGOT is 50 U/L.
  • Serum albumin ≥ 2 g/dL.
  • Adequate Cardiac Function Defined As:
  • Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of ≥ 50% by gated radionuclide study.
  • Must not have a history of myocardial infarction, severe or unstable angina, or peripheral vascular disease.
  • Adequate Blood Pressure Control Defined As:
  • A blood pressure (BP) ≤ the 95th percentile for age, height, and gender
  • Adequate Coagulation Defined As:
  • No evidence of active bleeding
  • PT and PTT ≤ 1.2 x upper limit of normal (ULN)
  • INR ≤1.2
  • Adequate Pancreatic Function Defined as:
  • Lipase ≤ 1.5 x upper limit of normal (ULN).

Who cannot join

  • Pregnancy or Breast-Feeding
  • Corticosteroids: Patients receiving chronically dosed corticosteroids within 7 days prior to enrollment are not eligible for this trial.
  • Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
  • Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.
  • Anti-GVHD agents post-transplant:
  • Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
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  • CYP3A4/5 Inhibitors:
  • Patients chronically receiving drugs that are known potent CYP3A4/5 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit, and grapefruit juice are not eligible
  • CYP3A4/5 Inducers:
  • Patients chronically receiving drugs that are known potent CYP3A4/5 inducers within 7 days prior to study enrollment, including but not limited to rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, and St John's wort are not eligible.
  • Anti-hypertensives: Patients who are receiving anti-hypertensive medications for control of blood pressure at the time of enrollment are not eligible for this trial.
  • Anti-coagulation: Patients who are currently receiving therapeutic anti-coagulation with heparin, low-molecular weight heparin or coumadin are not eligible for this trial.
  • Anti-inflammatory or anti-platelet agents: Patients who are currently receiving aspirin, ibuprofen or other non-steroidal anti-inflammatory drugs or anti-platelet agents are not eligible.
  • Patients must be able to swallow tablets whole.
  • Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 28 days prior to study enrollment. Patients who enter the study on thyroid replacement should have their medication adjusted to maintain TSH in the normal range.
  • Bleeding and Thrombosis:
  • Patients with evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis are not eligible:
  • History (within 180 days prior to study enrollment) of arterial thromboembolic events, including transient ischemic attack (TIA) or cerebrovascular accident (CVA).
  • History (within 180 days prior to study enrollment) of pulmonary embolism, DVT, or other venous thromboembolic event.
  • History of hemoptysis within 42 days prior to study enrollment.
  • Surgery: Patients who have had or are planning to have the following invasive procedures are not eligible:
  • Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment.
  • Subcutaneous port placement or central line placement is not considered major surgery but must be placed at least 3 days prior to enrollment for external lines and at least 7 days prior to enrollment for subcutaneous port.
  • Core biopsy within 7 days prior to enrollment.
  • Fine needle aspirate or central line placement within 7 days prior to enrollment.
  • CNS disease:
  • Patients who have a known primary or metastatic CNS tumor at the time of study enrollment are not eligible. A prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollment.
  • Patients who have a serious or non-healing wound, ulcer, or bone fracture at the time of study enrollment are not eligible.
  • Patients who have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study enrollment are not eligible.
  • Infection: Patients who have known HIV or an uncontrolled infection are not eligible.
  • Patients who have received a prior solid organ transplantation are not eligible.

Trial locations and contacts

21 sites in 2 countries.

21 sites in 2 countries

United States20 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48108

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Mark O Hatfield-Warren Grant Magnusun Clinical Center

    Bethesda, Maryland, 20892

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Ann and Robert H Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • University of Minnesota Cancer Center-Fairview

    Minneapolis, Minnesota, 55455

  • Columbia University Medical Center

    New York, New York, 10032

  • Childrens Hospital of Orange County

    Orange, California, 92868

  • Childrens Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • Seattle Children's Hospital

    Seattle, Washington, 98145

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Canada1 site

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase 1 Study of the VEGF Receptor Tyrosine Kinase Inhibitor Axitinib (INLYTA, IND# TBD) in Children With Recurrent or Refractory Solid Tumors

This trial will be the first study of axitinib in children and adolescents. The primary objective of this Phase 1 trial is to determine a maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of axitinib in pediatric patients with refractory solid tumors. Additional objectives include measurement of pharmacokinetic and pharmacodynamic parameters, description of the toxicity profile of this agent in children and adolescents, and assessment of response within the confines of a Phase 1 trial. A standard rolling 6 design will be used for dose escalation. Further development of axitinib will focus on development of a joint cooperative group (COG/ECOG) Phase 2 study of axitinib in pediatric, adolescent and young adult translocation renal cell carcinoma.

Being tested
Axitinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AxitinibDrug

    Also called AG-013736, INLYTA®

Study groups in NCT02164838
Study groupRoleWhat they receive
AxitinibExperimentalNot described
Receives: Drug: Axitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events as assessed by (CTCAE) version 4.0

    Measured: 28 days

  2. MTD of axitinib based on dose-limiting toxicity (DLT) at which fewer than one-third of patients experience DLT, as assessed by CTCAE version 4.0

    Measured: 28 days

  3. Pharmacokinetic Assessment of Axitinib Concentrations in Plasma Samples

    A descriptive analysis of pharmacokinetic (PK) parameters of axitinib will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters.

    Blood samples will be collected at the following time points:Day 1, Cycle 1: Pre-dose, and at 1, 2, 4, 6, and 8 hours after the AM dose on Day 1. Day 8, Cycle 1: Pre-dose, and at 1, 2, 4, 6, and 8 hours after the AM dose on Day 8.

    Measured: Day 1 and Day 8 of Cycle 1

Secondary outcomes (2)

  1. Evaluation of disease response to preliminarily define the antitumor activity of axitinib

    Patients will have tumor disease evaluations performed at the end of cycles 1, 3, and 5 and then every 3 cycles. Disease response will be assessed according to RECIST criteria for patients with solid tumors and will be reported descriptively. Analyses will be descriptive and exploratory and hypotheses generating in nature.

    Measured: up to 2 years

  2. Biomarkers of kidney injury during axitinib treatment

    Proteins in the blood (cystatin C and neutrophil gelatinase-associated lipocalcin (NGAL)) and urine (kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), creatinine and other markers of renal injury) will be measured before treatment and then weekly during Cycle 1 of axitinib treatment and at the end of Cycle 3

    Measured: Cycles 1 and 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2014 (estimated)
  2. Study startSep 2014
  3. Primary completion19 Oct 2017
  4. Study completion19 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02164838
Sponsor's protocol ID
ADVL1315
Status last verified
Jan 2018
First submitted
11 Jun 2014
Last updated
29 Jan 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Axitinib in people with Refractory or Recurrent Solid Tumors, Excluding CNS Tumors, run by Children's Oncology Group at 21 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events as assessed by (CTCAE) version 4.0 (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02164838.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2018.

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