SarcomaPhase 2PASART-2NCT02575066
Clinical Study of Concurrent Pazopanib and Radiotherapy for Non-metastatic Sarcoma Patients
A Phase 2 study testing external beam radiotherapy and pazopanib in people with Sarcoma and Soft Tissue Sarcomas, run by The Netherlands Cancer Institute at 3 sites in 2 countries.
Trial summary
Radiotherapy (RT) alone is able to induce a clinically significant effect with a variable pathologic response (a pathological complete remission, pCR, defined as ≥ 95%, or ≤ 5% remaining visible tumour cells) in only about 10% of cases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma, Soft Tissue Sarcomas
- What is being tested?
- external beam radiotherapy and pazopanib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 17 Mar 2016to 20 Mar 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed newly diagnosed intermediate to high grade soft tissue sarcoma localized to the extremities, trunk and chest wall or the head and neck area, for which the standard treatment is a combination of and radiotherapy and surgery(deep seated and/or > 5cm according to the RECIST 1.1 criteria and/or an anticipated close resection margin and/or grade II/III according to the WHO definition)
- Age ≥ 18 years
- WHO performance status of ≤ 1
- Able and willing to undergo blood sampling for PK and PD analysis
- Able to swallow and retain oral medication
- Able and willing to undergo MRI scanning
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- Able and willing to undergo tumor biopsies
- Adequate organ functions as described by the laboratory findings in the table 1. For thyroid function, the T4 and TSH values must be within normal values of the range of the participating centers
- Written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
Who cannot join
- Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
- Patients with recurrent sarcomas (even without prior radiotherapy)
- Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), osteosarcomas
- Clinically significant gastrointestinal abnormalities which might interfere with oral dosing diagnosed
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]
- Unstable or serious concurrent condition (e.g., active infection requiring systemic therapy)
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- Prolongation of corrected QT interval (QTc) > 480 msecs on ECG
- History of any of more of the following cardiovascular conditions within the past 6 months:
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Symptomatic peripheral vascular disease
- Coronary artery by-pass graft surgery
- Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
- History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
- Macroscopic hematuria
- Hemoptysis that is clinically relevant within 4 weeks of first dose of pazopanib
- Evidence of active bleeding or bleeding diathesis
- Prior major surgery or trauma within 28 days prior to first dose of study medication and/or presence of any non-healing wound, fracture, or ulcer
- Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study medication
- Biological therapy or treatment with an investigational agent within 28 days or five half-lives, whichever is longer prior to the first dose of study medication
- 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
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
- 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
- Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Netherlands2 sites
Antoni van Leeuwenhoek
Amsterdam, 1066CX
Leids Universitair Medisch Centrum
Leiden, 2333 ZA
About this study
Official title: Phase II Clinical Study of Concurrent Pazopanib for Non-metastatic Sarcoma Patients to be Treated With Radiotherapy, Localized in the Extremities, Trunk and Chest Wall or the Head and Neck Region (PASART-2)
Radiotherapy (RT) alone is able to induce a clinically significant effect with a variable pathologic response (a pathological complete remission, pCR, defined as ≥ 95%, or ≤ 5% remaining visible tumour cells) in only about 10% of cases. A prior phase I study (PASART-1; NCT01985295) suggested that 25 x 2 Gy preoperative RT in combination with once daily 800mg oral pazopanib is feasible, while inducing tissue replacing tumor that can consist of fibrosis and necrosis in 40% of thus treated patients.
During this study, the interim analysis showed that the combination treatment of preoperative radiation with orally pazopanib is more effective than was anticipated. For this reason, the pazopanib dose of 800 mg once daily is maintained but the RT dose is reduced to 18x2Gy instead of 25x2Gy. Predominant aim of this RT dose reduction is lowering the wound complication risk after preoperative radiotherapy.
Read the detailed description
Patients of the first part of the study received radiotherapy (25x2Gy) and pazopanib (QD 800 mg).
Patients of the second part of the study received/ will receive radiotherapy (18x2Gy) and pazopanib (QD 800 mg).
- Conditions
- Sarcoma, Soft Tissue Sarcomas
- Being tested
- external beam radiotherapy, pazopanib
- Keywords
- pazopanib, radiotherapy
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
external beam radiotherapyRadiation
Also called radiotherapy
external beam radiotherapy 25 x 2 Gy / 18 x 2 Gy
pazopanibDrug
pazopanib QD 800 mg
| Study group | Role | What they receive |
|---|---|---|
| radiotherapy combined with pazopanib | Other | patients during the first part of the study received concurrent radiotherapy (25x2Gy) and pazopanib (QD 800 mg). The patients of the second part of the study will receive concurrent radiotherapy (18x2Gy) and pazopanib (QD 800 mg). Receives: Radiation: external beam radiotherapy; Drug: pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological near complete remission of the resected specimen which has been treated with radiotherapy
Proportion of patients with resection specimens demonstrating induction of a pathological (near) complete remission (≥ 95% tumor regression). Pathological (near) complete remission is defined as ≥ 95% replacement of tumor with other tissue, usually fibrosis and) in the resection specimen post combined pazopanib and radiotherapy treatment
Measured: 6 weeks post treatment
Secondary outcomes (3)
Incidence toxicities measured by NCI-CTCAE v4.0 (radiotherapy alone, pazopanib alone or both) measured from start of treatment until 6 weeks post-treatment
Measured: during treatment and up to 6 weeks post treatment
Rate of response as measured by RECIST v 1.1 at 4 weeks after completing radiotherapy
Measured: 4 weeks post treatment
Incidence of acute post-operative wound complications up to 3 weeks (+/- 1 week) after surgery as defined in section 6.1.3 and reference 29 (see also appendix XII)
Measured: up to 3 weeks post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2015 (estimated)
- Study start17 Mar 2016
- Primary completion20 Mar 2019
- Study completion20 Mar 2019
Why it stopped: stopping rule
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SarcomaStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Marsden NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Rick Haas, MD, PhD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02575066
- Sponsor's protocol ID
- M15PAS
- Other IDs
- DSSG02
- Acronym
- PASART-2
- Status last verified
- Jun 2019
- First submitted
- 16 Sep 2015
- Last updated
- 27 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Study of Concurrent Pazopanib for Non-metastatic Sarcoma Patients to be Treated With Radiotherapy, Localized in the Extremities, Trunk and Chest Wall or the Head and Neck Region (PASART-2)
- ClinicalTrials.gov ID
- NCT02575066
- Acronym / sponsor ID
- PASART-2 / M15PAS
- Conditions
- Sarcoma, Soft Tissue Sarcomas
- Keywords
- pazopanib, radiotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: stopping rule
- Enrolment
- 25 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Royal Marsden NHS Foundation Trust
- Study start
- 17 Mar 2016 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 20 Mar 2019 (actual)
- First posted
- 14 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Radiotherapy (RT) alone is able to induce a clinically significant effect with a variable pathologic response (a pathological complete remission, pCR, defined as ≥ 95%, or ≤ 5% remaining visible tumour cells) in only about 10% of cases. A prior phase I study (PASART-1; NCT01985295) suggested that 25 x 2 Gy preoperative RT in combination with once daily 800mg oral pazopanib is feasible, while inducing tissue replacing tumor that can consist of fibrosis and necrosis in 40% of thus treated patients.
During this study, the interim analysis showed that the combination treatment of preoperative radiation with orally pazopanib is more effective than was anticipated. For this reason, the pazopanib dose of 800 mg once daily is maintained but the RT dose is reduced to 18x2Gy instead of 25x2Gy. Predominant aim of this RT dose reduction is lowering the wound complication risk after preoperative radiotherapy.
Detailed description
Patients of the first part of the study received radiotherapy (25x2Gy) and pazopanib (QD 800 mg).
Patients of the second part of the study received/ will receive radiotherapy (18x2Gy) and pazopanib (QD 800 mg).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| radiotherapy combined with pazopanib | Other | Radiation: external beam radiotherapy, Drug: pazopanibpatients during the first part of the study received concurrent radiotherapy (25x2Gy) and pazopanib (QD 800 mg). The patients of the second part of the study will receive concurrent radiotherapy (18x2Gy) and pazopanib (QD 800 mg). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed newly diagnosed intermediate to high grade soft tissue sarcoma localized to the extremities, trunk and chest wall or the head and neck area, for which the standard treatment is a combination of and radiotherapy and surgery(deep seated and/or > 5cm according to the RECIST 1.1 criteria and/or an anticipated close resection margin and/or grade II/III according to the WHO definition)
- Age ≥ 18 years
- WHO performance status of ≤ 1
- Able and willing to undergo blood sampling for PK and PD analysis
- Able to swallow and retain oral medication
Key exclusion criteria (25 listed)
- Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
- Patients with recurrent sarcomas (even without prior radiotherapy)
- Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), osteosarcomas
- Clinically significant gastrointestinal abnormalities which might interfere with oral dosing diagnosed
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| external beam radiotherapyAlso: radiotherapyexternal beam radiotherapy 25 x 2 Gy / 18 x 2 Gy | Radiation | radiotherapy combined with pazopanib |
| pazopanibpazopanib QD 800 mg | Drug | radiotherapy combined with pazopanib |
Primary outcome
pathological near complete remission of the resected specimen which has been treated with radiotherapy
Time frame: 6 weeks post treatment
Proportion of patients with resection specimens demonstrating induction of a pathological (near) complete remission (≥ 95% tumor regression). Pathological (near) complete remission is defined as ≥ 95% replacement of tumor with other tissue, usually fibrosis and) in the resection specimen post combined pazopanib and radiotherapy treatment
3 secondary outcomes
Incidence toxicities measured by NCI-CTCAE v4.0 (radiotherapy alone, pazopanib alone or both) measured from start of treatment until 6 weeks post-treatment
Time frame: during treatment and up to 6 weeks post treatment
Rate of response as measured by RECIST v 1.1 at 4 weeks after completing radiotherapy
Time frame: 4 weeks post treatment
Incidence of acute post-operative wound complications up to 3 weeks (+/- 1 week) after surgery as defined in section 6.1.3 and reference 29 (see also appendix XII)
Time frame: up to 3 weeks post surgery
Results and safety
The study was stopped early (reason given: stopping rule). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rick Haas, MD, PhD principal investigator
The Netherlands Cancer Institute
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing external beam radiotherapy and pazopanib in people with Sarcoma and Soft Tissue Sarcomas, run by The Netherlands Cancer Institute at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: stopping rule). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological near complete remission of the resected specimen which has been treated with radiotherapy (time frame: 6 weeks post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2019.