Efficacy of Pazopanib in Gastrointestinal Stromal Tumors (GIST)

NCT01323400 | Completed Phase 2

• 1 other identifier: PAZOGIST
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 13

Brief Summary

The purpose of this study is to evaluate the antitumor activity of pazopanib in patients with metastatic and/or locally advanced unresectable Gastrointestinal Stromal Tumors (GIST) resistant to imatinib and sunitinib. This is a phase II, randomized, multicentre study.

Conditions

GIST

Keywords

GIST; Resistant; Pazopanib; Tyrosine kinase inhibitor; Best supportive care; Progression-free survival; Overall survival; Objective response rate; Best response; Tolerance profile

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Within 16 months after the first inclusion, from the date of randomisation until the date of the first documented progression or death from any cause

Secondary Outcomes (8)

• Overall survival

  Within 16 months after the first inclusion, from the date of randomisation until the date of death from any cause

• Objective tumour response rate (RECIST v.1.1) at 4 months

  4 months after randomisation

• Best response (RECIST v.1.1) obtained during the study

  Within 16 months after the first inclusion

• Tolerance profile (NCI-CTCAE v.4.0)

  Within 16 months after the first inclusion

• Pattern of progression-free survival in the different molecular subtypes

  Within 16 months after the first inclusion, from the date of randomisation until the date of the first documented progression or death from any cause

Study Arms (2)

Pazopanib

EXPERIMENTAL

Pazopanib (800 mg/day) + Best supportive care according to the investigator's judgement. Pazopanib treatment is started on the day after randomization until radiological progression according to RECIST or until documented toxicity. In case of radiological progression, pazopanib may be continued (if the investigator wishes so) if a clinical benefit (pain reduction, 1 point increase in performance status) is observed.

Drug: Pazopanib; Other: Best supportive care

Best supportive care

OTHER

Best supportive care according to the investigator's judgment. Upon progression, compassionate treatment by pazopanib is possible according to eligibility criteria.

Other: Best supportive care

Interventions

Pazopanib DRUG

Pazopanib is administered orally at 800 mg/day (one dose every morning). A dose modification is possible in case of documented toxicity, according to specific algorithms.

Pazopanib

Best supportive care OTHER

Best supportive care according to the investigator's judgment (chemotherapy, immunotherapy, hormone therapy are not allowed). Non-targeted radiation therapy is tolerated, as antalgic strategy. Surgery is tolerated in case of emergency.

Best supportive care; Pazopanib

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histologically confirmed, unresectable, metastatic and/or locally advanced GIST.
• Progression or intolerance after treatment with at least imatinib (400 mg and 600/800 mg/d) then sunitinib at either 50mg/d on a 4w/6w schedule or 37.5mg/d continuous dosing. Intolerance is defined as documented grade 3 or higher toxicity requiring treatment interruption as documented in patient record.
• Measurable disease according to RECIST v1.1.
• Performance status ≤ 2 (WHO).
• Left Ventricular Ejection Fraction (LVEF) in accordance with local standards.
• Adequate organ system functions as defined below:
• Haematologic parameters
• Absolute neutrophil count (ANC) ≥ 1.5 G/L
• Haemoglobin ≥ 9 g/dL
• Platelets ≥ 100 G/L
• Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.2 X upper limit of normal (ULN) NB: Subjects receiving anticoagulation therapy are eligible if INR is stable and within the recommended range.
• Partial thromboplastin time (PTT) ≤ 1.2 X ULN
• Hepatic parameters
• Total bilirubin ≤ 1.5 X ULN

You may not qualify if:

• Prior malignant disease (other than GIST) within 3 years prior to entry, with the exception of in situ breast cell carcinoma or in situ carcinoma of the cervix or basocellular carcinoma or spinocellular carcinoma or bladder neoplasm, treated at least 6 months before and with no evidence of relapse.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for patients with previously-treated CNS metastases, who are asymptomatic and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. CNS screening with computed tomography \[CT\] or magnetic resonance imaging \[MRI\] is required only if clinically indicated or if the subject has a history of CNS metastases.
• Treatment with any of the following anti-cancer therapies:
• radiation therapy, surgery or tumour embolisation within 14 days prior to the first dose of pazopanib OR
• chemotherapy, biological therapy or investigational therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib.
• The analgesic radiation therapy is allowed (the irradiated lesions won't be chosen as target lesions during the evaluation)
• Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 followed and/or progressing in severity, except alopecia.
• Other uncontrolled severe medical conditions.
• Presence of uncontrolled infection.
• Clinically significant gastrointestinal abnormalities
• that may increase the risk for gastrointestinal bleeding.
• that may affect absorption of investigational product.
• Poorly controlled hypertension \[defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg\].
• NB: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be re-assessed on two occasions at \> 1 hour interval; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be \<140/90 mmHg for the subject to be eligible to the study.
• History of any cardiovascular pathology within the past 6 months.

Sponsors & Collaborators

• Centre Leon Berard: lead
• GlaxoSmithKline: collaborator

Study Sites (13)

Institut Bergonié

Bordeaux, France

Location

Centre Georges François Leclerc

Dijon, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, F-69008, France

Location

Hôpital de la Timone

Marseille, France

Location

Institut Paoli Calmette

Marseille, France

Location

Centre Alexis Vautrin

Nancy, France

Location

Institut de Cancérologie de l'Ouest

Nantes, France

Location

Hôpital St Antoine

Paris, France

Location

Hôpital Tenon

Paris, France

Location

CHU de Reims

Reims, France

Location

Institut Cancerologie Neuwirth

Saint-Priest-en-Jarez, France

Location

Institut Gustave Roussy

Villejuif, France

Location

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MeSH Terms

Interventions

pazopanib

Study Officials

• Jean-Yves BLAY, MD

  Centre Léon Bérard, LYON, FRANCE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 25, 2011
• Study Start: March 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: February 1, 2016
• Last Updated: February 25, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)