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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Solid Tumours

Treatments: Drug: pazopanib; Drug: topotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT00732420

HYT109091

Details and patient eligibility

About

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

Full 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

Enrollment: 68 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Screening

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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68 participants in 2 patient groups

Treatment Arm A

Experimental group

Description:

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.

Treatment:

Drug: pazopanib

Drug: topotecan

Treatment Arm B

Experimental group

Description:

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.

Treatment:

Drug: pazopanib

Drug: topotecan