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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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 (NS

Brief Summary: This randomized phase II/III trial studies how well pazopanib hydrochloride, combination chemotherapy, and radiation therapy work and compares it to radiation therapy alone or in combination with pazopanib hydrochloride or combination chemotherapy in treating patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin hydrochloride, 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 hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy works better when given with or without combination chemotherapy and/or pazopanib hydrochloride in treating patients with non-rhabdomyosarcoma soft tissue sarcomas.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To identify the dose of pazopanib (pazopanib hydrochloride) that is feasible when given in combination with radiation or chemoradiation in pediatric and adult patients newly diagnosed with unresected intermediate- and high-risk non-rhabdomyosarcoma soft tissue sarcomas (NRSTS).

II. To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative chemoradiation versus preoperative chemoradiation alone for potentially resectable > 5 cm, grade 3 intermediate to high risk chemotherapy-sensitive NRSTS in the phase II portion of the study for this cohort.

III. To compare the rates of near complete pathologic response (> 90% necrosis) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for potentially resectable intermediate to high risk adult and pediatric NRSTS in the phase II portion of the study for this cohort (using a phase II decision rule to go onto the phase III portion of the study).

IV. To compare the rates of event-free survival (EFS) with the addition of pazopanib to preoperative radiotherapy versus preoperative radiotherapy alone for localized intermediate to high risk adult and pediatric NRSTS in the phase III portion of the study for this cohort if the phase II decision rule is passed.

SECONDARY OBJECTIVES:

I. To estimate the rates of local failure, regional failure, distant metastasis free survival, disease-free survival, and overall survival with the addition of pazopanib to preoperative chemoradiation or preoperative radiation in intermediate to high risk adult and pediatric NRSTS.
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• EFS (Phase III) [ Time Frame: Time to the first occurrence of progression, relapse after response, secondary cancer or death from any cause, assessed up to 60 months ]
  The null (radiation therapy only) 5-year EFS for patients with localized unresectable chemo-resistant tumors is expected to be about 30%.
• Potential benefit for chemoradiotherapy plus pazopanib hydrochloride defined as protocol week 13 pathologic response (Phase II) [ Time Frame: Week 13 ]
  The expected null (chemotherapy only) pathologic response rate (90%+ necrosis at week 13) is 40%.
• Potential benefit for radiotherapy plus pazopanib hydrochloride defined as protocol week 10 pathologic response (Phase II/III) [ Time Frame: Week 10 ]
  The expected null (radiation therapy only) pathologic response rate (90%+ necrosis at Week 10) is 10%.

Original Primary Outcome:

• Potential benefit for chemoradiotherapy plus pazopanib hydrochloride defined as protocol week 13 pathologic response (Phase II) [ Time Frame: Week 13 ]
  The expected null (chemotherapy only) pathologic response rate (90%+ necrosis at week 13) is 40%.
• Potential benefit for radiotherapy plus pazopanib hydrochloride defined as protocol week 10 pathologic response (Phase II/III) [ Time Frame: Week 10 ]
  The expected null (radiation therapy only) pathologic response rate (90%+ necrosis at Week 10) is 10%.
• EFS (Phase III) [ Time Frame: Time to the first occurrence of progression, relapse after response, secondary cancer or death from any cause, assessed up to 60 months ]
  The null (radiation therapy only) 5-year EFS for patients with localized unresectable chemo-resistant tumors is expected to be about 30%.

Current Secondary Outcome:

• Adverse event profile of the treatments delivered (chemo-radiotherapy; radiotherapy) characterized using the current Common Terminology Criteria for Adverse Events version [ Time Frame: Up to 60 months ]
• Distant failure defined as disease recurrence at sites other than the primary site and diagnosis and nodes regional to that site (metastatic disease, whether or not present at diagnosis), with or without loco-regional failure [ Time Frame: Up to 60 months ]
  The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
• Local failure defined as disease recurrence only at the primary site of disease at diagnosis [ Time Frame: Up to 60 months ]
  The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
• Regional failure defined as disease recurrence at lymph nodes regional to the primary disease site, with or without local failure but without distant failure [ Time Frame: Up to 60 months ]
  The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.

Original Secondary Outcome:

• Local failure defined as disease recurrence only at the primary site of disease at diagnosis [ Time Frame: Up to 60 months ]
  The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
• Regional failure defined as disease recurrence at lymph nodes regional to the primary disease site, with or without local failure but without distant failure [ Time Frame: Up to 60 months ]
  The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
• Distant failure defined as disease recurrence at sites other than the primary site and diagnosis and nodes regional to that site (metastatic disease, whether or not present at diagnosis), with or without loco-regional failure [ Time Frame: Up to 60 months ]
  The relative risk of specific failure types will be estimated and compared descriptively using the Cox proportional hazard model.
• Adverse event profile of the treatments delivered (chemo-radiotherapy; radiotherapy) characterized using the current Common Terminology Criteria for Adverse Events version [ Time Frame: Up to 60 months ]

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 1, 2014
Date Started: July 2014
Date Completion:
Last Updated: May 24, 2017
Last Verified: May 2017