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Solid TumorsPhase 1/2TOPAZNCT02303028

Phase I Dose Escalation Study of Topotecan and Pazopanib in Children With Recurrent/Refractory Solid Tumours

A Phase 1/2 study testing Topotecan and Pazopanib in people with Solid Tumors, run by The Hospital for Sick Children at 10 sites in Canada.

Completed

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

Official record
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Trial summary

This is a phase I, dose escalation study where topotecan will be administered at lower doses given more frequently on a prolonged schedule (low dose metronomic; LDM), in combination with pazopanib administered in a specific dose range. Read more about this study

Who is it for?
Ages 2 to 21 years
Conditions the study is for
Solid Tumors
What is being tested?
Topotecan and Pazopanib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
10 sitesCanada
Study dates
Mar 2015to 17 Jun 2022
Phase
Phase 1/2
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 2 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Disease: Part 1-Relapsed or refractory solid tumours with histological verification of malignancy. Patients with CNS tumours are not eligible. Parts 2A and 2B - histological verification of one of the following solid tumours: Neuroblastoma or Rhabdomyosarcoma
  • Measurable or evaluable disease
  • No known curative therapy, or therapy proven to prolong survival with an acceptable QOL
  • Performance status: Lansky or Karnofsky ≥ 50%
  • ORGAN FUNCTION CRITERIA Bone Marrow Function
  • Peripheral ANC ≥ 1.5x109/L; Plt ≥ 100x109/L and Hgb ≥ 80 g/L (RBC transfusion permitted) Renal Function
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  • Measured creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2, OR a serum creatinine based on age/gender that meets the criteria outlined in the protocol
  • Urinalysis negative for protein, urine protein:creatinine ratio of ≤ 1, OR a 24-hour urine protein < 1000 mg/dL
  • <Gr.1 abnormalities of K, Ca (confirmed by ionized Ca),Mg or Ph (supplementation allowed) Liver Function
  • Total serum bilirubin ≤ 1.5xULN for age
  • SGPT (ALT) ≤ 2.5 x ULN and SGOT (AST) ≤ 2.5 x ULN
  • Serum albumin ≥ 20 g/L Cardiac Function
  • Adequate systolic ventricular function (LVSF≥ 27% or LVEF ≥ 50%)
  • QTc measured by ECG must be < 450 msec.
  • No history of MI, severe or unstable angina, peripheral vascular disease, or familial QTc prolongation Blood Pressure
  • Blood pressure ≤ 95th percentile for age, height, gender AND one of:
  • No current anti-hypertensive therapy, OR on stable doses of no more than one anti-hypertensive medication CNS Function
  • Subjects with known history of seizures must have well-controlled seizures and not receiving enzyme-inducing anti-convulsants Coagulation Function
  • INR ≤ 1.2 and PTT ≤ 1.2xULN
  • Prior Therapy
  • Myelosuppressive chemo must not have been given within 3 weeks of study enrolment (6 weeks if nitrosourea)
  • At least 7 days must have elapsed since 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 pegfilgrastim.
  • Biologic anti-neoplastic agent (including VEGF-blocking TKI) must not have been administered within 7 days of study enrolment
  • At least 3 half lives of the monoclonal antibody must have elapsed since the last dose administered
  • ≥ 2 weeks must have elapsed since local palliative XRT (small port); > 13 weeks since prior total body irradiation (TBI), craniospinal XRT or > 50% radiation of pelvis; or > 6 weeks if other substantial bone marrow irradiation
  • ≥ 8 weeks must have elapsed since MIBG therapy for neuroblastoma
  • At least 60 days must have elapsed from autologous or allogeneic stem cell transplant with no signs of GVHD.
  • At least 28 days from major surgery and wounds must be healed. At least 7 days from open and/or core biopsy.
  • Ability to take liquid medication by mouth

Who cannot join

  • Patients with CNS tumours or known CNS metastases
  • Pregnancy, breast feeding, or unwillingness to use effective contraception during the study
  • Subjects currently receiving:
  • Corticosteroids who haven't been on a stable or decreasing dose of corticosteroid for 7 days prior
  • Another investigational drug; other anti-cancer agents or radiation therapy
  • More than one medication for blood pressure control
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  • Therapeutic anticoagulation, including systemic use of warfarin, heparin, or low molecular weight heparin at any dose
  • Aspirin, and/or ibuprofen, or other NSAIDs
  • Drugs metabolized through several of the specific P450 cytochrome isoforms and those receiving drugs with a known risk of torsades de pointes
  • 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 enrolment.
  • Subjects who have an uncontrolled infection or serious non-healing would, ulcer or bone fracture.
  • Evidence of active bleeding, intratumoral haemorrhage, or bleeding diathesis, hemoptysis or any evidence of GI hemorrhage.
  • History (within 26 weeks prior to study enrolment) of arterial thromboembolic events (including TIA, CVA, or MI), pulmonary embolism, DVT or other venous thromboembolic event.
  • Evidence of tumour-related or other thrombus at time of enrolment
  • Major surgical procedure, laparoscopic procedure or significant traumatic injury within 28 days prior to Day 1 therapy. Open or core biopsy within 7 days prior to Day 1 of therapy. Fine needle aspirate within 48 hours prior to Day 1 therapy.
  • Previous, documented hypersensitivity reactions to topotecan or pazopanib
  • History of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days of study enrolment.
  • QTc > 450msec on baseline ECG or history of familial prolonged QTc syndrome
  • History of inflammatory lung disease secondary to exposure to mTOR or tyrosine kinase inhibitors.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Canada10 sites

  • Alberta Children's Hospital

    Calgary, Alberta

  • IWK Health Centre

    Halifax, Nova Scotia

  • McMaster Children's Hospital

    Hamilton, Ontario

  • Children's Hospital, London Health Sciences Centre

    London, Ontario

  • CHU St. Justine Hopital

    Montreal, Quebec

  • Children's Hospital of Eastern Ontario (CHEO)

    Ottawa, Ontario

  • Janeway Child Health Centre

    St. John's, Newfoundland and Labrador

  • Hospital for Sick Children

    Toronto, Ontario

  • BC Children's Hospital

    Vancouver, British Columbia

  • CancerCare Manitoba

    Winnipeg, Manitoba

Other trials in Canada

About this study

Official title: A Phase I and Enrichment Study of Low-dose Metronomic Topotecan and Pazopanib in Pediatric Patients With Recurrent or Refractory Solid Tumours

This is a phase I, dose escalation study where topotecan will be administered at lower doses given more frequently on a prolonged schedule (low dose metronomic; LDM), in combination with pazopanib administered in a specific dose range. The maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) will be evaluated for LDM topotecan in combination with pazopanib in children with recurrent or refractory solid tumours. Pharmacokinetic and pharmacodynamic studies will be conducted to further define the exposure to and activity of LDM topotecan in combination with pazopanib.

Conditions
Solid Tumors
Being tested
Topotecan and Pazopanib
Keywords
Pediatric, Solid Tumour

What participants receive

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

  • Topotecan and PazopanibDrug

    Also called Hycamtin, Votrient

    Low-dose metronomic Topotecan and Pazopanib will be escalated as per the dose escalation schema.

Study groups in NCT02303028
Study groupRoleWhat they receive
Topotecan and PazopanibExperimentalLow dose Topotecan will be given metronomically in combination with Pazopanib at the dose level assigned at study entry
Receives: Drug: Topotecan and Pazopanib

What is being measured

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

  1. Maximum tolerated dose (MTD) of low dose metronomic (LDM)Topotecan

    MTD is dependent on the number of subjects who experience a DLT at a given dose level

    Measured: Dose limiting toxicities (DLT) will be identified during the first cycle of therapy (28 days)

  2. Recommended phase 2 dose (RP2D) of LDM Topotecan

    The RP2D will be defined as the highest dose, at or below the MTD, at which the median number of cycles tolerated by subjects is ≥ 3.

    Measured: Dose limiting toxicities (DLT) will be identified during the first cycle of therapy (28 days)

Secondary outcomes (3)

  1. Anti-tumour activity of LDM Topotecan in combination with Pazopanib

    To preliminarily define the anti-tumour activity of LDM Topotecan in combination with pazopanib in pediatric solid tumours within the confines of a phase 1 study, and more specifically in cohorts of children with i) neuroblastoma and ii) rhabdomyosarcoma

    Measured: 24 months

  2. Pharmacokinetics of LDM Topotecan and Pazopanib

    To characterize the pharmacokinetics of LDM Topotecan and Pazopanib, as well as any drug-drug interactions

    Measured: 24 months

  3. Anti-angiogenic activity of LDM Topotecan and Pazopanib

    To assess the anti-angiogenic activity of this regimen by evaluating changes in plasma cytokines and angiogenic factors (CAF).

    Measured: 24 months

Timeline

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

  1. First posted27 Nov 2014 (estimated)
  2. Study startMar 2015
  3. Primary completion17 Jun 2022
  4. Study completion17 Jun 2022

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02303028
Sponsor's protocol ID
1000046233
Other IDs
IND.217
Acronym
TOPAZ
Status last verified
Jun 2022
First submitted
25 Nov 2014
Last updated
28 Jun 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Topotecan and Pazopanib in people with Solid Tumors, run by The Hospital for Sick Children at 10 sites in Canada.

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 29 inclusion and 19 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 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Maximum tolerated dose (MTD) of low dose metronomic (LDM)Topotecan (time frame: Dose limiting toxicities (DLT) will be identified during the first cycle of therapy (28 days)). The study lists 2 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 NCT02303028.

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 28 Jun 2022.

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