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

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

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

Study Overview

• Status: Completed
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: topotecan; Drug: pazopanib

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

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • GSK Investigational Site
  • Utrecht, Netherlands, 3584 CX
    • GSK Investigational Site
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
First course tolerability with rising dose of topotecan to determine the maximum tolerated dose of topotecan when given with pazopanib daily.	5 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Indications of efficacy through tumour shrinkage. Specific biomarker analysis.	12 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2008
• Primary Completion (Actual): June 12, 2013
• Study Completion (Actual): June 12, 2013

Study Registration Dates

• First Submitted: August 11, 2008
• First Submitted That Met QC Criteria: August 11, 2008
• First Posted (Estimate): August 12, 2008

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Phase I; Advanced Solid Tumors; pazopanib; topotecan
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan
• Other Study ID Numbers: HYT109091