Pazopanib as Front-Line Therapy in Patients With Non-Resectable or Metastatic Soft Tissue Sarcomas Who Are Not Candidates for Chemotherapy

NCT02300545 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201501057
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 7

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  16 weeks

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  Until disease progression (median follow-up of 10.83 months with full range 0.787-42.26 months)

• Overall Survival (OS)

  Until death (median follow-up of 10.83 months with full range 0.787-42.26 months)

• Median Overall Change in Quality of Life

  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)

  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)

  From baseline through completion of treatment

Study Arms (1)

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.

Drug: Pazopanib

Interventions

Pazopanib DRUG

Also known as: GW786034, Votrien

Pazopanib

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (7)

Mayo Clinic - Phoenix

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Sarcoma

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Brian A. Van Tine, M.D., Ph.D.
• Organization: Washington University School of Medicine

bvantine@wustl.edu

314-747-8475

Study Officials

• Brian A Van Tine, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 20, 2014
• First Posted: November 25, 2014
• Study Start: April 8, 2015
• Primary Completion: May 31, 2019
• Study Completion: July 11, 2020
• Last Updated: August 5, 2020
• Results First Posted: June 9, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)