Sarcoma, Soft TissuePhase 2NCT02300545
Pazopanib as Front-Line Therapy in Patients With Non-Resectable or Metastatic Soft Tissue Sarcomas Who Are Not Candidates for Chemotherapy
A Phase 2 study testing Pazopanib in people with Sarcoma, Soft Tissue and Soft Tissue Sarcoma, run by Washington University School of Medicine at 7 sites in United States.
Trial summary
Pazopanib is FDA approved as a second line and beyond treatment for metastatic soft tissue sarcoma. There is a population of elderly and debilitated soft tissue sarcoma patients that are not fit for standard first line chemotherapy that is doxorubicin based. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma, Soft Tissue, Soft Tissue Sarcoma
- What is being tested?
- Pazopanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 7 sitesUnited States
- Study dates
- 8 Apr 2015to 11 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 diagnosis of nonresectable or metastatic soft tissue sarcoma. The following histologies are excluded: embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumors, primitive neuroectodermal tumors, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma, and mixed mesodermal tumors of the uterus.
- Evaluable disease by imaging or physical exam OR measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Not a candidate for chemotherapy as determined by treatment physician
- Age ≥ 18 years
- ECOG performance status ≤ 2
- Normal bone marrow and organ function as defined below:
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- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin ≥ 9.0 g/dL
- PT or INR ≤ 1.2 x IULN (if not receiving anticoagulation therapy)
- PTT ≤ 1.2 x IULN (if not receiving anticoagulation therapy)
- Total bilirubin ≤ 1.5 x IULN or ≤ 3.0 x IULN with normal AST and ALT in patients with Gilbert's disease
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m2 for patients with creatinine levels above 1.5 mg/dL
- UPC < 1 or, if UPC ≥ 1, 24-hour urine protein < 1 g; use of urine dipstick for renal function assessment is not acceptable.
- Notes:
- Subjects may not have had a transfusion within 7 days of screening assessments. Concomitant elevation of bilirubin and AST/ALT above the IULN is not allowed.
- Patients receiving anticoagulation therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.
- Ability to swallow and retain oral tablets.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document.
Who cannot join
- Eligible for cytotoxic chemotherapy.
- Prior systemic therapy for this type of sarcoma. Neoadjuvant or adjuvant therapy more than two years prior would not apply.
- Prior treatment with any VEGFR tyrosine kinase inhibitor.
- Administration of any non-oncologic investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose of pazopanib.
- Use of a strong CYP3A4 inhibitor less than 14 days prior to initiation of study treatment
- A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
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- Known brain metastases.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study.
- Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity (except alopecia).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled seizure disorder, or psychiatric illness/social situations that would limit compliance with study requirements.
- 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 pectoris, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure as defined by the New York Heart Association
- Poorly controlled hypertension (defined as systolic blood pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg). Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure must be reassessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between antihypertensive medication initiation or adjustment and blood pressure measurement. These three values should be averaged to obtain the mean diastolic and systolic blood pressures, which must be < 140/90 mmHg in order for a patient to be eligible for the study.
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding, including (but not limited to) active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other GI conditions with increased risk of perforation, history of abdominal fistula or intra-abdominal abscess within 28 days prior to beginning study treatment.
- Clinically significant gastrointestinal abnormalities that may affect absorption of pazopanib, including (but not limited to) malabsorption syndrome or major resection of the stomach or small bowel.
- History of cerebrovascular accident including transient ischemic attack, pulmonary embolism (PE) (including asymptomatic or previously treated PE), or untreated deep venous thrombosis within the past 6 months. Patients with DVT who are being treated with therapeutic anti-coagulating agents are eligible.
- Major surgery or trauma within 28 days prior to first dose of pazopanib and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement 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. Note: lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions). Large protruding endobronchial lesions in the mail or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed. Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of thee bronchi are allowed.
- Recent hemoptysis (≥ ½ teaspoon of red blood within 8 weeks before first dose of pazopanib).
- Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 14 days of study entry.
- Known HIV-positivity. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Northwestern University
Chicago, Illinois, 60611
University of Iowa
Iowa City, Iowa, 52242
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
University of Wisconsin Clinical Science Center
Madison, Wisconsin, 53792
Mayo Clinic - Phoenix
Phoenix, Arizona, 85054
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase II Study of Pazopanib as Front-Line Therapy in Patients With Non-Resectable or Metastatic Soft Tissue Sarcomas Who Are Not Candidates for Chemotherapy
Pazopanib is FDA approved as a second line and beyond treatment for metastatic soft tissue sarcoma. There is a population of elderly and debilitated soft tissue sarcoma patients that are not fit for standard first line chemotherapy that is doxorubicin based. As pazopanib is well tolerated with minimal side effects, the investigators propose a phase II study to evaluate pazopanib as a first-line agent in patients with non-resectable or metastatic disease who are not candidates for cytotoxic chemotherapy.
- Conditions
- Sarcoma, Soft Tissue, Soft Tissue Sarcoma
- Being tested
- Pazopanib
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Also called GW786034, Votrien
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib | Experimental | Pazopanib will be started at a dose of 200 mg BID for four days, then escalated to a dose of 400 mg BID for four days, then escalated once more to a dose of 800 mg QD for the duration of participation (or until dose reduction, if necessary). Pazopanib should be taken orally without food at least one hour before or two hours after a meal. One cycle of pazopanib is 28 days. Receives: Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate
Clinical benefit rate = complete response (CR) + partial response (PR) + stable disease (SD)
- CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
- PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: 16 weeks
Secondary outcomes (5)
Progression-free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Measured: Until disease progression (median follow-up of 10.83 months with full range 0.787-42.26 months)
Overall Survival (OS)
Measured: Until death (median follow-up of 10.83 months with full range 0.787-42.26 months)
Median Overall Change in Quality of Life
- Quality of life will be measured using the Functional Assessment of Cancer Therapy-General (FACT-G7) validated survey
- 7 statements where the participant can indicate 0 (not at all) up to 4 (very much). The statements include 1) I have lack of energy; 2) I have pain; 3) I have nausea; 4) I worry that my condition will get worse; 5) I am sleeping well; 6) I am able to enjoy life; 7) I am content with the quality of my life right now.
- The first 4 statements will negatively affect the total score and the last 3 statements will positively affect the total score
- Each item is scored and then added together, multiplied by 7, and divided by the number of items
- Total score calculation ranges from 0-28. The higher the score, the better the quality of life
Measured: Change from baseline to end of treatment (median length of treatment 70 days (5-515 days)))
Clinical Outcome Associated With Serum sVEGFR2 Levels (Serum Levels of sVEGFR2 at Each Time Point Will Plotted and Pearson or Spearman's Correlation Coefficient)
The serum levels of sVEGFR2 at each time point will plotted and Pearson or Spearman's correlation coefficient will be calculated to explore their relationship.
Measured: From baseline through completion of treatment
Clinical Outcome Associated With Serum PICG Levels (Serum Levels of PIGF at Each Time Point Will Plotted and Pearson or Spearman's Correlation Coefficient)
The serum levels of PIGF at each time point will plotted and Pearson or Spearman's correlation coefficient will be calculated to explore their relationship.
Measured: From baseline through completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2014 (estimated)
- Study start8 Apr 2015
- Primary completion31 May 2019
- Study completion11 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sarcoma, Soft TissueStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Brian A Van Tine, M.D., Ph.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02300545
- Sponsor's protocol ID
- 201501057
- Status last verified
- Jul 2020
- First submitted
- 20 Nov 2014
- Last updated
- 5 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pazopanib as Front-Line Therapy in Patients With Non-Resectable or Metastatic Soft Tissue Sarcomas Who Are Not Candidates for Chemotherapy
- ClinicalTrials.gov ID
- NCT02300545
- Acronym / sponsor ID
- 201501057
- Conditions
- Sarcoma, Soft Tissue, Soft Tissue Sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 8 Apr 2015 (actual)
- Primary completion
- 31 May 2019 (actual)
- Study completion
- 11 Jul 2020 (actual)
- First posted
- 25 Nov 2014 (estimated)
- Results
- Posted 9 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pazopanib is FDA approved as a second line and beyond treatment for metastatic soft tissue sarcoma. There is a population of elderly and debilitated soft tissue sarcoma patients that are not fit for standard first line chemotherapy that is doxorubicin based. As pazopanib is well tolerated with minimal side effects, the investigators propose a phase II study to evaluate pazopanib as a first-line agent in patients with non-resectable or metastatic disease who are not candidates for cytotoxic chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pazopanib | Experimental | Drug: PazopanibPazopanib will be started at a dose of 200 mg BID for four days, then escalated to a dose of 400 mg BID for four days, then escalated once more to a dose of 800 mg QD for the duration of participation (or until dose reduction, if necessary). Pazopanib should be taken orally without food at least one hour before or two hours after a meal. One cycle of pazopanib is 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically confirmed diagnosis of nonresectable or metastatic soft tissue sarcoma. The following histologies are excluded: embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumors, primitive neuroectodermal tumors, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma, and mixed mesodermal tumors of the uterus.
- Evaluable disease by imaging or physical exam OR measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- Not a candidate for chemotherapy as determined by treatment physician
- Age ≥ 18 years
- ECOG performance status ≤ 2
Key exclusion criteria (22 listed)
- Eligible for cytotoxic chemotherapy.
- Prior systemic therapy for this type of sarcoma. Neoadjuvant or adjuvant therapy more than two years prior would not apply.
- Prior treatment with any VEGFR tyrosine kinase inhibitor.
- Administration of any non-oncologic investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the first dose of pazopanib.
- Use of a strong CYP3A4 inhibitor less than 14 days prior to initiation of study treatment
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 |
|---|---|---|
| PazopanibAlso: GW786034, Votrien | Drug | Pazopanib |
Primary outcome
Clinical Benefit Rate
Time frame: 16 weeks
Clinical benefit rate = complete response (CR) + partial response (PR) + stable disease (SD) * CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. * PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
5 secondary outcomes
Progression-free Survival (PFS)
Time frame: Until disease progression (median follow-up of 10.83 months with full range 0.787-42.26 months)
Overall Survival (OS)
Time frame: Until death (median follow-up of 10.83 months with full range 0.787-42.26 months)
Median Overall Change in Quality of Life
Time frame: Change from baseline to end of treatment (median length of treatment 70 days (5-515 days)))
Clinical Outcome Associated With Serum sVEGFR2 Levels (Serum Levels of sVEGFR2 at Each Time Point Will Plotted and Pearson or Spearman's Correlation Coefficient)
Time frame: From baseline through completion of treatment
Clinical Outcome Associated With Serum PICG Levels (Serum Levels of PIGF at Each Time Point Will Plotted and Pearson or Spearman's Correlation Coefficient)
Time frame: From baseline through completion of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- 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.
Brian A Van Tine, M.D., Ph.D. principal investigator
Washington University School of Medicine
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pazopanib in people with Sarcoma, Soft Tissue and Soft Tissue Sarcoma, run by Washington University School of Medicine at 7 sites in United States.
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 21 inclusion and 22 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: finished, as of the sponsor's last update on 5 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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?
Yes. Results are posted in the registry (first posted 9 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Benefit Rate (time frame: 16 weeks). 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 5 Aug 2020.