Combined Modality Treatment of Sarcomas of the Extremities (PASART-1)

October 8, 2015 updated by: The Netherlands Cancer Institute

Phase I Clinical Study of a Combined Modality Treatment of Sarcomas of the Extremities With Radiotherapy (RT) and Dose-escalation of Pazopanib

In this study, we aim to define the recommended dose of a VEGFR-TKI (pazopanib) in combination with RT pre-operatively given.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Study design A dose escalation trial of Pazopanib, starting at 400mg daily, orally in combination with the standard 25 x 2Gy preoperative radiotherapy in newly diagnosed extremity sarcoma patients. Dose of pazopanib will be escalated via 600mg to maximally 800mg. Overall treatment time of pazopanib is 40 days.

Treatment plan: Pazopanib Dose level Dose of pazopanib orally, once daily, # patients

  1. (starting) 400 mg 3
  2. 600 mg 3
  3. (maximum) 800 mg 3

Treatment plan: radiotherapy RT is given during 5 weeks with a once daily fraction of 2 Gray (50 Gray in 25 daily fractions)

RT planning: The dose planning should be performed by CT based Intensity Modulated RT (IMRT) or 3 Dimensional Conformal RT (3D-RT) according to the local planning protocol of the participating institute.

Dose specification: According to the ICRU 50/62.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Noord Holland
      • Amsterdam, Noord Holland, Netherlands, 1066CX
        • The Netherlands Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically confirmed newly diagnosed intermediate to high grade soft tissue sarcoma of and localized to the extremities or head and neck area for which the treatment is a combination of both surgery and radiotherapy (deep seated, > 5cm according to the RECIST 1.1 criteria, grade II/III according to the WHO definition).
  2. Age > 18 years.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  4. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  5. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

6 Able to swallow and retain oral medication. 7. A life expectancy of at least 12 weeks. 8. Adequate organ function.

-

Exclusion Criteria:

  1. Prior malignancies; except subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
  2. Patients with recurrent sarcomas (even without prior radiotherapy).
  3. Ewing sarcoma and other PNET family tumours, rhabdomyosarcomas (both pediatric and adult), osteosarcomas.

  4. Clinically significant gastrointestinal abnormalities which might interfere with oral dosing diagnosed as:

    • Active peptic ulcer disease.
    • Known intraluminal metastatic lesions with suspected bleeding.
    • Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation.
    • History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
    • Major resection of the stomach or small bowel.
  5. Uncontrolled hypertension.
  6. Unstable or serious concurrent condition (e.g., active infection requiring systemic therapy).
  7. Prolongation of corrected QT interval (QTc) >480 msecs.

  8. History of any one of more of the following cardiovascular conditions within the past 6 months:

    1. Cardiac angioplasty or stenting.
    2. Myocardial infarction.
    3. Unstable angina.
    4. Symptomatic peripheral vascular disease.
    5. Coronary artery by-pass graft surgery.
    6. Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA).
    7. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  9. Macroscopic hematuria
  10. Haemoptysis that is clinically relevant within 4 weeks of first dose of study drug.
  11. Evidence of active bleeding or bleeding diathesis.
  12. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
  13. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug.
  14. Biological therapy or treatment with an investigational agent within 28 days or 5 half-lives, whichever is longer prior to the first dose of study drug.
  15. Prohibited medications listed in the protocol for 14 days or five half-lives of a drug (whichever is longer) prior to Visit 1 and for the duration of the study should not be taken.
  16. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.
  17. Pregnancy or lactating.

  18. Hypothyroidism.

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: cohort

Dose level Dose of pazopanib orally, once daily, # patients -1 200 mg --

  1. (starting) 400 mg 3
  2. 600 mg 3
  3. (maximum) 800 mg 3
Drug: pazopanib
A dose escalation trial of Pazopanib, starting at 400mg daily, orally in combination with the standard 25 x 2Gy preoperative radiotherapy in newly diagnosed extremity sarcoma patients. Dose of pazopanib will be escalated via 600mg to maximally 800mg. Overall treatment time of pazopanib is 40 days.
Other Names:
  • Compound Number: GW786034

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose limiting toxicity
Time Frame: 14 weeks
To study the safety and feasibility of adding 6 weeks of orally administered Pazopanib to 25 x 2Gy in 5 weeks preoperative radiotherapy in extremity or head and neck area soft tissue sarcoma patients (to identify the Dose Limiting Toxicity (DLT) and the Recommend Phase II Dose (RPTD) if pazopanib is added to 50 Gy pre-operatively)
14 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
the exploration/feasibility of dynamic imaging
Time Frame: 14 weeks
The secondary objective is to explore the feasibility to perform perfusion weighted MRI imaging regarding tumor respons to RT and neoangio genesis inhibitor by pazopanib.
14 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The Netherlands Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rick Haas, MD,PhD, NKI

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 7, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 15, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 9, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 8, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • M09RTP
  • 2009-014901-15 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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