Open-label Study of Topotecan and Pazopanib in Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00732420
First received: August 11, 2008
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

To determined what dose of topotecan can be safely given with daily pazopanib.


Condition Intervention Phase
Solid Tumours
Drug: topotecan
Drug: pazopanib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: A Phase I Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Two Schedules of Oral Topotecan in Combination With Pazopanib in Subjects With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • First course tolerability with rising dose of topotecan to determine the maximum tolerated dose of topotecan when given with pazopanib daily. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Indications of efficacy through tumour shrinkage. Specific biomarker analysis. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: September 2008
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm A
Daily oral pazopanib in combination with weekly oral topotecan. Initially rising dose to determine the maximum tolerated dose: finally an expanded cohort treated at the maximum tolerated dose.
Drug: topotecan
Topoisomerase I inhibition.
Drug: pazopanib
Tyrosine kinase inhibitor
Experimental: Treatment Arm B
Daily oral pazopanib in combination with oral topotecan given for 5 consecutive days every 21 days. Initially rising dose to determine the maximum tolerated dose; finally an additional cohort of patients treated at the maximum tolerated dose.
Drug: topotecan
Topoisomerase I inhibition.
Drug: pazopanib
Tyrosine kinase inhibitor

Detailed Description:

A Phase I Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Two Schedules of Oral Topotecan in combination with Pazopanib in Subjects with Advanced Solid Tumors

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria -

  • signed, written informed consent.
  • at least 18 years of age.
  • ECOG performance status 0 or 1.
  • Subjects must have histologically or cytologically confirmed diagnosis of advanced cancer and a solid tumor malignancy that has relapsed or is refractory to standard therapy or for which there is no established therapy.
  • able to swallow and retain oral medications.
  • females are eligible to enter and participate in this study providing adequate established contraception is being practiced.

Exclusion Criteria

  • had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)
  • received an investigational drug within 30 days or 5 half-lives (whichever is longer).
  • received prior treatment with pazopanib/investigational anti-angiogenic compounds.
  • presence of uncontrolled infection.
  • pregnant or lactating.
  • poorly controlled hypertension (SBP of ? 140 mmHg, or DBP of ? 90 mmHg.
  • Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.-
  • arterial thrombi, myocardial infarction, admission for unstable angina, uncontrolled or symptomatic arrhythmia, cardiac angioplasty, or stenting within the last 6 months.
  • any unresolved bowel obstruction or diarrhea ? Grade 1.
  • received an allogeneic bone marrow transplant.
  • known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan.
  • any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study.
  • psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • clinical history, current alcohol or illicit drug use which, in the judgment of the investigator, would interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732420

Locations
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1066 CX
GSK Investigational Site
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00732420     History of Changes
Other Study ID Numbers: HYT109091
Study First Received: August 11, 2008
Last Updated: July 30, 2013
Health Authority: United States: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by GlaxoSmithKline:
pazopanib
Phase I
topotecan
Advanced Solid Tumors

Additional relevant MeSH terms:
Neoplasms
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014