Trial of Pazopanib in Patients With Solitary Fibrous Tumor and Extraskeletal Myxoid Chondrosarcoma

NCT02066285 | Completed Phase 2

• 2 other identifiers: GEIS-322013-005456-15
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 7

Brief Summary

Phase II, open-label, non-randomized, international multicenter clinical trial with two strata (SFT and EMC). 8 sites in Spain, 5 sites in Italy and 5 sites in France. Patients will receive oral pazopanib at 800 mg once daily continuously. Patients will continue to receive treatment until there is evidence of progressive disease, unacceptable toxicity, non-compliance, withdrawn consent or investigator decision. The main goal is to determine the objective response rate (ORR) (confirmed complete response \[CR\] and partial response \[PR\]) in patients with unresectable, locally advanced or metastatic solitary fibrous tumor and extraskeletal myxoid chondrosarcoma, using Choi and RECIST 1.1 criteria respectively.

Conditions

Solitary Fibrous Tumor; Extraskeletal Myxoid Chondrosarcoma

Keywords

Solitary fibrous tumor; Extraskeletal myxoid chondrosarcoma; Unresectable; Locally advanced; Metastatic disease

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective response rate (ORR) (confirmed complete response \[CR\] and partial response \[PR\]), measured using Choi and RECIST 1.1 criteria. Response criteria will be based on the baseline identification of target lesions and follow-up until tumor progression.

  48 weeks

Secondary Outcomes (4)

• Efficacy of pazopanib

  48 weeks

• Overall survival (OS)

  72 weeks

• Clinical benefit rate (CBR)

  48 weeks

• Long term safety profile of pazopanib

  48 weeks

Study Arms (1)

Pazopanib

EXPERIMENTAL

Single arm of pazopanib 800 mg (2x400 mg or 4x200 mg) given as a single agent once daily continuously.

Drug: Pazopanib

Interventions

Pazopanib DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Also known as: Votrient

Pazopanib

Eligibility Criteria

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

You may qualify if:

• Informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
• Age ≥ 18 years or legal age of consent if greater than 18 years.
• Histologic diagnosis of solitary fibrous tumor (stratum 1) or extraskeletal myxoid chondrosarcoma (stratum 2) (unresectable, locally advanced or metastatic disease) confirmed by central pathology review.
• Patients with metastatic tumor suitable for complete resection can be recruited. In absence of progressive disease these patients should be treated with the study drug for at least 6 months.
• For patients who have received previous anticancer treatments, progressive disease must be demonstrated within 6 months prior to enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Measurable disease according to Choi (SFT) and RECIST 1.1 (EMC) criteria.
• Patients could have received a maximum of 4 lines of chemotherapy for metastatic disease prior to trial enrollment.
• Patients must be able to swallow and retain the study drug.
• Adequate organ system function as defined in protocol.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment. All patients (both male and female) must agree to use effective contraception methods, as defined in the protocol.
• Left ventricular ejection fraction (LVEF) above the lower limit of normal for the institution, either by echocardiogram or MUGA.

You may not qualify if:

• Prior malignancy, except patients who have had another malignancy and have been disease-free for 10 years, or those with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
• Central nervous system metastases at baseline, with the exception of patients who have previously-treated central nervous system metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6-month time interval.
• Patients who have received previous antiangiogenic agents.
• Significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding.
• Significant gastrointestinal abnormalities that may affect absorption of investigational product.
• Corrected QT interval (QTc) \> 480 msecs.
• 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 II, III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\].
• History of cerebrovascular accident.
• Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (catheter placement and similar procedures are not considered to be major surgery).
• Evidence of active bleeding or bleeding diathesis.
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
• Recent hemoptysis (\>=½ teaspoon of red blood within 8 weeks before first dose of study drug).
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety, provision of informed consent, or compliance to study procedures.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (7)

H. Son Espases

Palma de Mallorca, Balearic Islands, Spain

Location

H. Universitario de Canarias

Santa Cruz de Tenerife, Santa Cruz De Tenerife, 38320, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

H. Miguel Servet

Zaragoza, Spain

Location

Related Publications (4)

• Napolitano A, Moura DS, Hindi N, Mondaza-Hernandez JL, Merino-Garcia JA, Ramos R, Dagrada GP, Stacchiotti S, Graziano F, Vincenzi B, Martin-Broto J. Expression of p53 as a biomarker of pazopanib efficacy in solitary fibrous tumours: translational analysis of a phase II trial. Ther Adv Med Oncol. 2022 Aug 6;14:17588359221116155. doi: 10.1177/17588359221116155. eCollection 2022.

  PMID: 35965642 DERIVED

• Martin-Broto J, Cruz J, Penel N, Le Cesne A, Hindi N, Luna P, Moura DS, Bernabeu D, de Alava E, Lopez-Guerrero JA, Dopazo J, Pena-Chilet M, Gutierrez A, Collini P, Karanian M, Redondo A, Lopez-Pousa A, Grignani G, Diaz-Martin J, Marcilla D, Fernandez-Serra A, Gonzalez-Aguilera C, Casali PG, Blay JY, Stacchiotti S. Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Mar;21(3):456-466. doi: 10.1016/S1470-2045(19)30826-5. Epub 2020 Feb 14.

  PMID: 32066540 DERIVED

• Stacchiotti S, Ferrari S, Redondo A, Hindi N, Palmerini E, Vaz Salgado MA, Frezza AM, Casali PG, Gutierrez A, Lopez-Pousa A, Grignani G, Italiano A, LeCesne A, Dumont S, Blay JY, Penel N, Bernabeu D, de Alava E, Karanian M, Morosi C, Brich S, Dagrada GP, Vallacchi V, Castelli C, Brenca M, Racanelli D, Maestro R, Collini P, Cruz J, Martin-Broto J. Pazopanib for treatment of advanced extraskeletal myxoid chondrosarcoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2019 Sep;20(9):1252-1262. doi: 10.1016/S1470-2045(19)30319-5. Epub 2019 Jul 19.

  PMID: 31331701 DERIVED

• Martin-Broto J, Stacchiotti S, Lopez-Pousa A, Redondo A, Bernabeu D, de Alava E, Casali PG, Italiano A, Gutierrez A, Moura DS, Pena-Chilet M, Diaz-Martin J, Biscuola M, Taron M, Collini P, Ranchere-Vince D, Garcia Del Muro X, Grignani G, Dumont S, Martinez-Trufero J, Palmerini E, Hindi N, Sebio A, Dopazo J, Dei Tos AP, LeCesne A, Blay JY, Cruz J. Pazopanib for treatment of advanced malignant and dedifferentiated solitary fibrous tumour: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2019 Jan;20(1):134-144. doi: 10.1016/S1470-2045(18)30676-4. Epub 2018 Dec 18.

  PMID: 30578023 DERIVED

MeSH Terms

Conditions

Solitary Fibrous Tumors; Chondrosarcoma, Extraskeletal Myxoid; Neoplasm Metastasis

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Josefina Cruz, MD

  Hospital Universitario de Canarias

  STUDY DIRECTOR

• Javier Martín, MD

  Hospital Son Espases

  STUDY DIRECTOR

• Antonio López-Pousa, MD

  Hospital Sant Pau

  PRINCIPAL INVESTIGATOR

• M. Ángeles Vaz, MD

  Hospital Universitario Ramon y Cajal

  PRINCIPAL INVESTIGATOR

• Andrés Redondo, MD

  Hospital La Paz

  PRINCIPAL INVESTIGATOR

• Javier Martínez-Trufero, MD

  Hospital Miguel Servet

  PRINCIPAL INVESTIGATOR

• Pilar Blay, MD

  Hospital Central de Asturias

  PRINCIPAL INVESTIGATOR

• Pilar Sancho, MD

  Hospital Virgen del Rocío

  PRINCIPAL INVESTIGATOR

• Jean Yves Blay, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

• Silvia Stacchiotti, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 19, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2019
• Study Completion: March 24, 2023
• Last Updated: March 27, 2023

Record last verified: 2023-03

Locations

ES (7)