DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Information source: The Hospital for Sick Children
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Solid Tumors; Central Nervous System Tumors

Intervention: Topotecan and Pazopanib (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: The Hospital for Sick Children

Official(s) and/or principal investigator(s):
Sylvain Baruchel, Study Chair, Affiliation: The Hospital for Sick Children

Overall contact:
Rachel Polintan, Phone: 416-813-7654, Ext: 228486, Email: rachel.polintan@sickkids.ca

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 a fixed dose of pazopanib. 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 including CNS tumours. Pharmacokinetic and pharmacodynamic studies will be conducted to further define the exposure to and activity of LDM topotecan in combination with pazopanib.

Clinical Details

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

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

Primary outcome:

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

Recommended phase 2 dose (RP2D) of LDM Topotecan

Secondary outcome:

Anti-tumour activity of LDM Topotecan in combination with Pazopanib

Pharmacokinetics of LDM Topotecan and Pazopanib

Anti-angiogenic activity of LDM Topotecan and Pazopanib

Eligibility

Minimum age: 2 Years. Maximum age: 21 Years. Gender(s): Both.

Criteria:

INCLUSION: 1. Disease: Part 1-Relapsed or refractory solid tumours including CNS tumours; Part 2A-Neuroblastoma, Part 2B Rhabdomyosarcoma 2. Measurable or evaluable disease 3. No known curative therapy, or therapy proven to prolong survival with an acceptable QOL 4. Organ Function Criteria

- Peripheral ANC ≥ 1,500/μL; Plt ≥ 100,000/ and Hb ≥ 80 g/L (RBC transfusion

permitted)

- 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

- allowed)

- 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

- Adequate systolic ventricular function

- 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 ≤ 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

- Subjects with known history of seizures must have well-controlled seizures and

not receiving enzyme-inducing anti-convulsants

- INR ≤ 1. 2 and PTT ≤ 1. 2xULN

5. 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. 6. Ability to take liquid medication by mouth EXCLUSION: 1. Patients with DIPG, or known CNS metastases 2. Pregnancy, breast feeding, or unwillingness to use effective contraception during the study 3. 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

- 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. 4. Subjects who have an uncontrolled infection; serious or non-healing wound, ulcer, or bone fracture 5. Evidence of active bleeding, intratumoral haemorrhage, or bleeding diathesis 6. Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy 7. Previous, documented hypersensitivity reactions to topotecan or pazopanib 8. History of abdominal fistula, GI perforation, or intra-abdominal abscess within 28 days of study enrolment

Locations and Contacts

Rachel Polintan, Phone: 416-813-7654, Ext: 228486, Email: rachel.polintan@sickkids.ca

Alberta Children's Hospital, Calgary, Alberta, Canada; Not yet recruiting
Pina Giuliano
Victor Lewis, Principal Investigator

BC Children's Hospital, Vancouver, British Columbia, Canada; Not yet recruiting
Stephanie Badour
Jessica Davis
Rebecca Deyell, Principal Investigator

CancerCare Manitoba, Winnipeg, Manitoba, Canada; Not yet recruiting
Rebekah Hiebert
Kathy Hjalmarsson
Donna Wall, Principal Investigator

IWK Health Centre, Halifax, Nova Scotia, Canada; Not yet recruiting
Lynn Russell
Jason Berman, Principal Investigator

Children's Hospital of Eastern Ontario (CHEO), Ottawa, Ontario, Canada; Not yet recruiting
Isabelle LaForest
Donna Johnston, Principal Investigator

The Hospital for Sick Children, Toronto, Ontario, Canada; Recruiting
Rachel Polintan
Sylvain Baruchel, Principal Investigator

CHU St. Justine Hopital, Montreal, Quebec, Canada; Not yet recruiting
Dominique Lafreniere
Monia Marzouki, Principal Investigator

Additional Information

Starting date: March 2015
Last updated: March 18, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017