Spotlight on Clinical Trials: 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

April 13, 2017

 

Researchers from multiple DF/HCC member institutions, Boston Children's Hospital, Dana-Farber Cancer Institute, and Massachussets General Hospital, are participating in a nationwide study of pazopanib in sarcoma.

This randomized phase II/III trial, led by principal investigator Alison Friedmann, MD (DFCI), will compare various combinations of pazopanib, chemotherapy, and radiation therapy in patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can be removed by surgery.

Yen-Lin Evelyn Chen, MD

Yen-Lin Evelyn Chen, MD

“Soft tissue sarcomas in adult and pediatric patients have high rates of failure despite improvement in surgery and radiation,” said Yen-Lin Evelyn Chen, MD (MGH), a radiation oncologist and researcher on the trial. She added that “there is a need to find new effective chemotherapy to treat these patients in the neoadjuvant setting; i.e., up front for patients who don't have metastatic disease.”

Currently, it is unclear whether radiation therapy works better when given with or without combination chemotherapy and/or pazopanib in treating patients with non-rhabdomyosarcoma soft tissue sarcomas. To answer this question, 4 regimens are being evaluated: pazopanib and chemoradiation, chemoradiation alone, pazopanib plus radiation therapy, and radiation therapy alone. 

Pazopanib is a kinase inhibitor that targets several members of the vascular endothelial growth factor receptor family and is currently approved for use in advanced renal cell carcinoma and advanced soft tissue sarcoma after prior chemotherapy.

The PAZNTIS study started in 2014 and has an estimated enrollment of 340, with a final collection date of June 2018 for the primary outcome measure.

According to Chen, this study builds on two recent Phase I/II studies by the Children’s Oncology Group (COG) and NRG Oncology to explore the role of pazopanib in sarcoma. “This is the first time that the two cooperative groups (i.e., the COG and the NRG) have come together to run a study in any malignancy,” she noted.

"Importantly," says Chen, "the trial focuses on the adolescent/young adult patients, a population that is often underrepresented in clinical trials.” 

According to Chen, 82 patients have been accrued nationwide to date. They are anticipating the first interim analysis to be available for the first 30 evaluable patients in the phase II portion by the middle of this year. 

Study Design:

Regimens A, B, C, and D will be compared. In Regimen A, IV doxorubicin and ifosfamide will be given with radiation therapy, and pazopanib. In Regimen B, chemoradiation at the same dose will be given, but without pazopanib, for Regimen C, pazopanib and radiation will be given. Patients in a fourth group receive radiation only (Regimen D). During the induction phase, patients receive oral pazopanib once daily during weeks 1-9. Radiation therapy is given during weeks 1-7. Surgery takes place on week 10. After surgery, during the continuation phase, patients receive pazopanib from weeks 13-25 and radiation for a total dose of 50Gy during weeks 13-16. 

Included in the study are children aged 2 and older and adults who have newly diagnosed and histopathologically confirmed, potentially resectable non-rhabdomyosarcoma soft tissue sarcomas of the trunk, shoulders, and hips.

The primary outcome for the phase III portion of the trial is event-free survival, assessed for up to 60 months. After 13 weeks, the potential benefit for chemoradiotherapy plus pazopanib will be measured by evaluating pathologic response (phase II). The potential benefit for radiotherapy plus pazopanib will be measured by pathologic response at week 10 (phase II/III). Secondary outcomes include adverse events and distant, regional, and local disease recurrence.

Phase II/III Trial
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, IND# 118613)
Principal Investigator: Alison Friedmann, MD (MGH)
NIH Trial Number: NCT02180867
DF/HCC Protocol Number: 16-704

The trial is starting to recruit patients. Find more information at ClinicalTrials.gov.

— By Emma Hitt Nichols, PhD