NCT02180867|Active Not RecruitingPhase 2Results

Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

Pazopanib Neoadjuvant Trial in Non-Rhabdomyosarcoma Soft Tissue Sarcomas (PAZNTIS): A Phase II/III Randomized Trial of Preoperative Chemoradiation or Preoperative Radiation Plus or Minus Pazopanib (NSC# 737754)

National Cancer Institute (NCI)ClinicalTrials.gov

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6 other identifiers

NCI-2014-01340ARST1321s14-02023U10CA098543U10CA180830U10CA180886

Study Type

interventional

Target

140

Locations

3 countries

Sites

381

Timeline

RegisteredJul 2014

StartedJul 2014

CompletionDec 2026

Brief Summary

This randomized phase II/III trial studies how well pazopanib, when combined with chemotherapy and radiation therapy or radiation therapy alone, work in the treatment of patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can eventually be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether these therapies can be safely combined and if they work better when given together in treating patients with non-rhabdomyosarcoma soft tissue sarcomas.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

140

participants targeted

Target at P75+ for phase_2

Timeline

7mo left

Started Jul 2014

Longer than P75 for phase_2

Geographic Reach

3 countries

381 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

12.5 years study duration

Study Progress96%

Jul 2014Dec 2026

First Submitted

Initial submission to the registry

July 1, 2014

Completed

2 days until next milestone

First Posted

Study publicly available on registry

July 3, 2014

Completed

8 days until next milestone

Study Start

First participant enrolled

July 11, 2014

Completed

5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2019

Completed

1.3 years until next milestone

Results Posted

Study results publicly available

October 9, 2020

Completed

6.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 24, 2026

Expected

Last Updated

May 4, 2026

Status Verified

December 1, 2025

Enrollment Period

5 years

First QC Date

July 1, 2014

Results QC Date

June 24, 2020

Last Update Submit

May 1, 2026

Conditions

Alveolar Soft Part Sarcoma Epithelioid Malignant Peripheral Nerve Sheath Tumor Epithelioid Sarcoma Extraskeletal Myxoid Chondrosarcoma Intimal Sarcoma Leiomyosarcoma Liposarcoma Low Grade Myofibroblastic Sarcoma Malignant Peripheral Nerve Sheath Tumor Myxofibrosarcoma Myxoinflammatory Fibroblastic Sarcoma Nerve Sheath Neoplasm Synovial Sarcoma Angiomatoid Fibrous Histiocytoma Atypical Fibroxanthoma Clear Cell Sarcoma of Soft Tissue Extraskeletal Osteosarcoma Fibrohistiocytic Neoplasm Fibrosarcoma Inflammatory Myofibroblastic Tumor Liver Embryonal Sarcoma Low Grade Fibromyxoid Sarcoma Malignant Skin Granular Cell Tumor Malignant Triton Tumor Mesenchymal Chondrosarcoma Myxoid Chondrosarcoma PEComa Pericytic Neoplasm Plexiform Fibrohistiocytic Tumor Sclerosing Epithelioid Fibrosarcoma Skin Glomus Tumor Stage IB Soft Tissue Sarcoma AJCC v7 Stage IIB Soft Tissue Sarcoma AJCC v7 Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Undifferentiated High Grade Pleomorphic Sarcoma of Bone

Outcome Measures

Primary Outcomes (5)

Feasible Dose: Pediatric
The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in pediatric unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and \< 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.
After the first 6 weeks of Induction
Feasible Dose: Adult
The dose of pazopanib that is feasible when given in combination with radiation or chemoradiation in adult unresected intermediate- and high-risk NRSTS patients. Initially, up to 10 patients (minimum of 3 patients ≥ 2 and \< 18 years of age and 3 patients ≥ 18 years of age) eligible for each of the two study cohorts were non-randomly assigned (to generate 8 patients evaluable for toxicity) to receive treatment with pazopanib at dose level 1. A protocol-defined list of pazopanib-associated adverse events were defined as dose-limiting toxicities. The pazopanib dose determined to be feasible was based on the number of patient-reported dose-limiting toxicities encountered.
After the first 6 weeks of Induction
Percentage of Chemoradiotherapy Patients With Positive Pathologic Response at Week 13
A responder is defined by more than (90% tumor necrosis at week 13). A non-responder has less than 90% necrosis or progressive disease before week 13.
Week 13 after induction
Percentage of Radiotherapy Patients With Positive Pathologic Response at Week 10
A responder is defined by more than 90% tumor necrosis at week 10. A non-responder has less than 90% necrosis or progressive disease before week 10.
Week 10 after induction
Percentage of Radiotherapy Patients Failure Free at 5 Years Following Study Entry
Time to the first occurrence of relapse, progression, secondary cancer or death from any cause.
From enrollment to up to 60 months

Secondary Outcomes (4)

Percentage of Patients Local Failure Free at 5 Years Following Study Entry
From enrollment to up to 60 months
Percentage of Patients Regional Failure Free at 5 Years Following Study Entry
From enrollment to up to 60 months
Percentage of Patients Distant Failure Free at 5 Years Following Study Entry
From enrollment to up to 60 months
Percentage of Patients Who Experienced Grade 3 or Higher Toxicity Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Reporting of adverse events was required from the start of protocol therapy and until 30 days from the last administration of study drugs; up to 1 year

Other Outcomes (5)

Relative Frequency of Actionable Mutations
At diagnosis
Prevalence of Circulating Tumor DNA (ctDNA)
At diagnosis
Mean Pharmacokinetic Parameters of Doxorubicin and Pazopanib
Up to 48 hours after the end of infusion
+2 more other outcomes

Study Arms (4)

Regimen A (pazopanib, chemoradiation)

EXPERIMENTAL

See Regimen A Detailed Description.

Drug: DoxorubicinDrug: Doxorubicin HydrochlorideDrug: IfosfamideDrug: PazopanibDrug: Pazopanib HydrochlorideRadiation: Radiation TherapyProcedure: Therapeutic Conventional Surgery

Regimen B (chemoradiation)

EXPERIMENTAL

See Regimen B Detailed Description.

Drug: DoxorubicinDrug: Doxorubicin HydrochlorideDrug: IfosfamideRadiation: Radiation TherapyProcedure: Therapeutic Conventional Surgery

Regimen C (pazopanib, radiation therapy)

EXPERIMENTAL

INDUCTION PHASE: Patients receive pazopanib PO QD on weeks 1-9. Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: Patients receive pazopanib PO QD on weeks 13-25. If applicable, patients undergo additional radiation therapy at week 13.

Drug: PazopanibDrug: Pazopanib HydrochlorideRadiation: Radiation TherapyProcedure: Therapeutic Conventional Surgery

Regimen D (radiation therapy)

EXPERIMENTAL

INDUCTION PHASE: Patients undergo radiation therapy on weeks 1-7. SURGERY: Patients undergo surgery on week 10. CONTINUATION PHASE: If applicable, patients undergo additional radiation therapy at week 13.

Radiation: Radiation TherapyProcedure: Therapeutic Conventional Surgery

Interventions

Therapeutic Conventional SurgeryPROCEDURE

Undergo surgery

Regimen A (pazopanib, chemoradiation)Regimen B (chemoradiation)Regimen C (pazopanib, radiation therapy)Regimen D (radiation therapy)

DoxorubicinDRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Regimen A (pazopanib, chemoradiation)Regimen B (chemoradiation)

Doxorubicin HydrochlorideDRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

Regimen A (pazopanib, chemoradiation)Regimen B (chemoradiation)

IfosfamideDRUG

Given IV

Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

Regimen A (pazopanib, chemoradiation)Regimen B (chemoradiation)

PazopanibDRUG

Given PO

Also known as: GW786034

Regimen A (pazopanib, chemoradiation)Regimen C (pazopanib, radiation therapy)

Pazopanib HydrochlorideDRUG

Given PO

Also known as: GW 786034B, GW-786034B, GW786034B, Pazopater, Votrient

Regimen A (pazopanib, chemoradiation)Regimen C (pazopanib, radiation therapy)

Radiation TherapyRADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Regimen A (pazopanib, chemoradiation)Regimen B (chemoradiation)Regimen C (pazopanib, radiation therapy)Regimen D (radiation therapy)

Eligibility Criteria

Age2 Years+

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

Note: eligible patients must have a body surface area \>= 0.5 m\^2 AND be able to swallow whole tablets
Newly diagnosed and histopathologically confirmed, potentially resectable NRSTS of the extremity and trunk will be eligible for the chemotherapy or non-chemotherapy cohort based on:
Evidence of chemotherapy sensitivity of the histologic sarcoma subtype based on existing evidence from prior clinical trials
Sufficient risk of metastatic disease to warrant chemotherapy based on size and grade and
Medically deemed able or unable to undergo chemotherapy
Notes: an incisional biopsy or core biopsy is preferred; fine needle aspiration biopsy is not acceptable to establish the diagnosis
ELIGIBLE SITES:
Extremities: upper (including shoulder) and lower (including hip)
Trunk: body wall
INELIGIBLE SITES: Head and neck, visceral organs (with the exception of embryonal sarcoma of the liver), retroperitoneum, peritoneum, pelvis within the confines of the bony pelvis
ELIGIBILITY FOR CHEMOTHERAPY COHORT:
Stage T2a/b (\> 5 cm) and grade 2 or 3 AND
One of the following chemosensitive histologies as defined in the World Health Organization (WHO) classification of soft tissue tumors (with some evidence of good response to chemoradiation and of sufficient high risk of metastases, or clear evidence of metastases):
Unclassified soft tissue sarcomas that are too undifferentiated to be placed in a specific pathologic category in the WHO classification (often called "undifferentiated soft tissue sarcoma" or "soft tissue sarcoma not otherwise specified \[NOS\]")
Synovial sarcoma
+46 more criteria

You may not qualify if:

Patients with grade 1 NRSTS tumors of any size are not eligible
Patients with known central nervous system (CNS) metastases are not eligible; Note: brain imaging is not an eligibility requirement
Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: patients aged \> 17 years with excess of 2.5 mL of hemoptysis are not eligible)
Patients with gross total resection of the primary tumor prior to enrollment on ARST1321 are NOT eligible; patients who have experienced tumor recurrence after a gross total tumor resection are NOT eligible
Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is defined as follows:
Patients aged =\< 17 years: greater than 95th percentile systolic and diastolic blood pressure based on age and height which is not controlled by one anti-hypertensive medication
Patients aged \> 17 years: systolic blood pressure \>= 140 mmHg and/or diastolic blood pressure \>= 90 mmHg that is not controlled by one anti-hypertensive medication
Prior Therapy:
Patients must have had no prior anthracycline (e.g., doxorubicin, daunorubicin) or ifosfamide chemotherapy
Patients must have had no prior use of pazopanib or similar multi-targeted tyrosine kinase inhibitors (TKI)
Patients must have had no prior radiotherapy to tumor-involved sites
Note: patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements; patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded
Other types of invasive malignancy that are not disease free within 3 years except for non-melanoma skin cancer, lentigo maligna, any carcinoma-in-situ or prostate cancer with low risk factors
CYTOCHROME P450 3A4 (CYP3A4) substrates WITH narrow therapeutic indices: patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; Note: the use of fentanyl is permitted
CYP3A4 Inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin many non-nucleoside reverse-transcriptase inhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible
+33 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (381)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

The Kirklin Clinic at Acton Road

Birmingham, Alabama, 35243, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Alaska Breast Care and Surgery LLC