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

Primary Purpose

Solitary Fibrous Tumor, Extraskeletal Myxoid Chondrosarcoma

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Pazopanib
Sponsored by
Grupo Espanol de Investigacion en Sarcomas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solitary Fibrous Tumor focused on measuring Solitary fibrous tumor, Extraskeletal myxoid chondrosarcoma, Unresectable, Locally advanced, Metastatic disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.
  • Patients in France will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • 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.
  • Unable or unwilling to discontinue use of prohibited medications listed in the protocol for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
  • Treatment with any of the following anti-cancer therapies:

Radiation therapy, surgery or tumor embolization within 28 days prior to the first dose of pazoapnib or Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib

  • Administration of any non-oncologic drug within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment.
  • Ongoing toxicity from prior anti-cancer therapy that is >Grade 1 (except anemia, see Table 1 above) and/or that is progressing in severity, except alopecia.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.

Sites / Locations

  • H. Son Espases
  • H. Universitario de Canarias
  • Hospital de la Santa Creu i Sant Pau
  • Hospital La Paz
  • Hospital Ramón y Cajal
  • Hospital Universitario Virgen del Rocío
  • H. Miguel Servet

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pazopanib

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Efficacy of pazopanib
Efficacy measured by the progression-free survival (PFS) rate assessed by median time
Overall survival (OS)
Overall survival (OS) measured since treatment start date until date of death, whichever the cause
Clinical benefit rate (CBR)
Clinical benefit rate (CBR). Patients who have reached CR, PR or SD during 6 months or more, presenting clinical improvement of symptoms, will be considered as having experienced clinical benefit.
Long term safety profile of pazopanib
Long term safety profile of pazopanib, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using NCI-CTCAE 4.0.

Full Information

First Posted
February 14, 2014
Last Updated
March 24, 2023
Sponsor
Grupo Espanol de Investigacion en Sarcomas
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1. Study Identification

Unique Protocol Identification Number
NCT02066285
Brief Title
Trial of Pazopanib in Patients With Solitary Fibrous Tumor and Extraskeletal Myxoid Chondrosarcoma
Official Title
A Phase II Open-Label Trial of Pazopanib Administered as a Single Agent in Patients With Unresectable or Metastatic Solitary Fibrous Tumor (SFT) and Extraskeletal Myxoid Chondrosarcoma (EMC)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
June 2014 (Actual)
Primary Completion Date
December 2019 (Actual)
Study Completion Date
March 24, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grupo Espanol de Investigacion en Sarcomas

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
To estimate the sample size for stratum 1 (SFT), a Simon's optimal 2-stage phase II design has been used, having considered the published response rate based on Choi criteria in SFT patients which correspond to 40% in monotherapy. For a design with P0=0.40, P1=0.60; α=0.1 and β=0.1. At the first stage, 18 patients should be enrolled into the study, if there are fewer than 8 responses (7 or less) the trial will be terminated and it will be concluded that pazopanib is not sufficiently active. At the second stage, another 28 patients (total 46 patients) would be enrolled into the study. To reject the null hypothesis for the SFT stratum 23 responses or more (Choi criteria), out of the 46 patients, are needed. To estimate the simple size for stratum 2 (EMC), a Simon's optimal 2-stage phase II design has been used, having considered the very scarce published information on response rate based on RECIST criteria. For a design with P0= 0.05, P1= 0.25, α=0.1 and β=0.1. At the first stage, 9 patients should be enrolled into the study, if there are not responses the trial will be terminated and it will be concluded that pazopanib is not sufficiently active. If there is at least 1 response in this first stage, the trial will be continued and at the second stage, another 15 patients (total 24 patients) would be enrolled into the study. To reject the null hypothesis for the EMC stratum 3 responses or more (RECIST criteria), out of the 24 patients, are needed. For variables that follow binomial distributions (e.g. response rate) frequency and percentages will be calculated, together with their corresponding exact 95% confidence intervals. For time-to-event variables (e.g. PFS or OS) Kaplan-Meier estimations will be used. To analyze the reduction of risk and the influence of other variables on time-to-event variables Cox Regression will be applied. To correlate pharmacodynamics markers and biomarkers with clinical response standard methods for bivariate and multivariate regression and correlation will be used.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solitary Fibrous Tumor, Extraskeletal Myxoid Chondrosarcoma
Keywords
Solitary fibrous tumor, Extraskeletal myxoid chondrosarcoma, Unresectable, Locally advanced, Metastatic disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pazopanib
Arm Type
Experimental
Arm Description
Single arm of pazopanib 800 mg (2x400 mg or 4x200 mg) given as a single agent once daily continuously.
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Other Intervention Name(s)
Votrient
Intervention Description
Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
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.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Efficacy of pazopanib
Description
Efficacy measured by the progression-free survival (PFS) rate assessed by median time
Time Frame
48 weeks
Title
Overall survival (OS)
Description
Overall survival (OS) measured since treatment start date until date of death, whichever the cause
Time Frame
72 weeks
Title
Clinical benefit rate (CBR)
Description
Clinical benefit rate (CBR). Patients who have reached CR, PR or SD during 6 months or more, presenting clinical improvement of symptoms, will be considered as having experienced clinical benefit.
Time Frame
48 weeks
Title
Long term safety profile of pazopanib
Description
Long term safety profile of pazopanib, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using NCI-CTCAE 4.0.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Patients in France will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Exclusion Criteria: 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. Unable or unwilling to discontinue use of prohibited medications listed in the protocol for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study. Treatment with any of the following anti-cancer therapies: Radiation therapy, surgery or tumor embolization within 28 days prior to the first dose of pazoapnib or Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib Administration of any non-oncologic drug within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment. Ongoing toxicity from prior anti-cancer therapy that is >Grade 1 (except anemia, see Table 1 above) and/or that is progressing in severity, except alopecia. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Josefina Cruz, MD
Organizational Affiliation
Hospital Universitario de Canarias
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Javier Martín, MD
Organizational Affiliation
Hospital Son Espases
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Antonio López-Pousa, MD
Organizational Affiliation
Hospital Sant Pau
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
M. Ángeles Vaz, MD
Organizational Affiliation
Hospital Universitario Ramon y Cajal
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrés Redondo, MD
Organizational Affiliation
Hospital La Paz
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Javier Martínez-Trufero, MD
Organizational Affiliation
Hospital Miguel Servet
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pilar Blay, MD
Organizational Affiliation
Hospital Central de Asturias
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pilar Sancho, MD
Organizational Affiliation
Hospital Virgen del Rocío
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jean Yves Blay, MD
Organizational Affiliation
Centre Leon Berard
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Silvia Stacchiotti, MD
Organizational Affiliation
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Official's Role
Study Director
Facility Information:
Facility Name
H. Son Espases
City
Palma De Mallorca
State/Province
Islas Baleares
Country
Spain
Facility Name
H. Universitario de Canarias
City
Tenerife
State/Province
Santa Cruz De Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
Country
Spain
Facility Name
Hospital La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
H. Miguel Servet
City
Zaragoza
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
35965642
Citation
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.
Results Reference
derived
PubMed Identifier
32066540
Citation
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.
Results Reference
derived
PubMed Identifier
31331701
Citation
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. Erratum In: Lancet Oncol. 2019 Oct;20(10):e559.
Results Reference
derived
PubMed Identifier
30578023
Citation
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.
Results Reference
derived

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

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