Study of Pazopanib Versus Placebo as Maintenance Therapy for Advanced Soft Tissue Sarcoma

NCT02367651 | Withdrawn Phase 2

• 1 other identifier: 201187
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Pazopanib monotherapy is approved by the Food and Drug Administration (FDA), European Medicines Agency, and other regulatory authorities worldwide for the treatment of patients with advanced renal cell carcinoma and patients with advanced soft tissue sarcoma (STS) who received prior chemotherapy. Based on the improved progression-free survival and sustained responses observed in a pivotal Phase 3, randomized, placebo-controlled study, it is hypothesized that pazopanib may have a role in a maintenance setting for STS in maintaining the initial response to chemotherapy and delaying the need for further treatment at relapse and its associated toxicity and impact on health-related quality-of-life. This Phase 2, randomized, double-blind, placebo-controlled study will evaluate maintenance therapy with pazopanib versus placebo in subjects with advanced or metastatic STS who have not progressed after 4 to 6 cycles of first-line anthracycline-based chemotherapy. Approximately 188 eligible subjects will be randomized in a 1:1 ratio to treatment with pazopanib 800 milligrams (mg) daily or placebo. Study completion will be the point at which 70% of randomized subjects have died. Once a subject has objective evidence of disease progression, the subject will be managed as per standard practice by their physician. Subjects will continue to be followed for second progression, health related quality of life, survival until study completion, withdrawal of consent, or early termination of the study.

Conditions

Sarcoma, Soft Tissue

Keywords

Soft tissue sarcoma; Pazopanib; Tyrosine kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS is defined as time from randomization to development of disease progression or death due to any cause. Disease progression will be evaluated based on investigators' radiologic assessments by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1

  At Day 57 and every 8 weeks thereafter until disease progression or death (assessed up to 2 years)

Secondary Outcomes (10)

• Overall survival (OS)

  At Day 57, then every 8 weeks until disease progression, and every 3 months thereafter until death (assessed up to 2 years)

• Disease control rate (DCR)

  At 4 months after randomization

• Safety and tolerability as assessed by physical examination findings

  From Day 1 up to end of treatment (assessed up to 2 years)

• Safety and tolerability as assessed by temperature measurement

  From Day 1 up to end of treatment (assessed up to 2 years)

• Safety and tolerability as assessed by systolic and diastolic blood pressure measurement

  From Day 1 up to end of treatment (assessed up to 2 years)

Study Arms (2)

Pazopanib

EXPERIMENTAL

Subjects will receive pazopanib 800 mg once daily during each 28-day treatment period until disease progression, unacceptable adverse event (AE)/serious adverse event (SAE), death or withdrawal of consent

Drug: Pazopanib 800 mg

Placebo

PLACEBO COMPARATOR

Subjects will receive placebo once daily during each 28-day treatment period until disease progression, unacceptable AE/SAE, death or withdrawal of consent

Drug: Placebo

Interventions

Pazopanib 800 mg DRUG

Aqueous film-coated, oval-shaped, white tablets containing either 200 mg or 400 mg pazopanib

Pazopanib

Placebo DRUG

Tablets matching the 200 mg and 400 mg pazopanib tablets

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed written informed consent before performing study-specific procedures or assessments and are willing to comply with treatment and follow-up.
• Age \>= 18 years

You may not qualify if:

• Completed 4 to 6 cycles of first-line anthracycline-based chemotherapy for metastatic disease without disease progression.
• Note: Subjects must have no evidence of radiological progression as confirmed by Computed Tomography (CT)/ Magnetic Resonance Imaging (MRI) within 4 weeks before randomization and no signs of clinical progression before randomization.
• The date of study randomization must be 3 to 8 weeks following the last dose of chemotherapy. All chemotherapy-related side effects (except alopecia) must have resolved to grade 1 or better.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Able to swallow and retain oral tablets.
• Adequate baseline organ function
• Baseline Left Ventricular Ejection Fraction (LVEF) above lower limit of normal (LLN) based on institution's normal range.
• Corrected QT interval (QTc) \<450 milliseconds (msec) or QTc \<480 msec for subjects with bundle branch block. For subject eligibility and withdrawal, Bazett's QT correction formula (QTcB) will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
• Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective contraception, as defined in Study Protocol during the study and for 14 days following the last dose of study treatment.
• Note: Female subjects who are lactating must discontinue nursing before the first dose of study treatment and refrain from nursing from the first dose until 14 days following the last dose of study treatment.
• Prior malignancy. Note: Subjects who have had another malignancy and have been disease-free for 3 years or more, or subjects with a history of completely resected non-melanoma skin carcinoma or successfully treated in situ carcinoma are eligible.
• Any of the following tumor types: Adipocytic sarcoma (all subtypes) , All rhabdomyosarcoma that are NOT alveolar or pleomorphic, Chondrosarcoma, Osteosarcoma, Ewing tumors / primitive neuroectodermal tumor (PNET), Gastro-intestinal stromal tumors (GIST), Dermofibromatosis sarcoma protuberans, Inflammatory myofibroblastic sarcoma, Malignant mesothelioma, Mixed mesodermal tumors of the uterus (carcinosarcoma), Subjects with low grade histology (French Fédération Nationale des Centres de Lutte Contre le Cancer \[FNCLCC\] grade 1 or those with incomplete grading information FNCLCC grade X)
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding within 28 days before beginning study treatment.
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: Malabsorption syndrome, Major resection of the stomach or small bowel
• History of any one or more of the following cardiovascular conditions within the past 6 months: Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina, Coronary artery bypass graft surgery, Symptomatic peripheral vascular disease, Class III or IV congestive heart failure (CHF), as defined by the New York Heart Association (NYHA)

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Sarcoma

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2015
• First Posted: February 20, 2015
• Study Start: June 1, 2015
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: October 12, 2016

Record last verified: 2016-10