Phase I clinical study of a combined modality treatment of sarcomas of the extremities or in head and neck area with radiotherapy (RT) and dose-escalation of Pazopanib

Completed

• Conditions: sarcoma; soft tissue tumor; 10028389

• Registration Number: NL-OMON39288
• Lead Sponsor: ederlands Kanker Instituut

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

1. Histologically confirmed newly diagnosed intermediate to high grade soft tissue
sarcoma of and localized to the extremities or head and neck for which the treatment is a
combination of both surgery and radiotherapy (deep seated, > 5cm according to the RECIST criteria, grade II/III according to the WHO definition).
2. Age >= 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
4. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
5. Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
6. No prior malignancies; except subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
7. No clinically significant gastrointestinal abnormalities which might interfere with oral dosing diagnosed as:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with suspected bleeding
• Inflammatory bowel disease
• Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
• Malabsorption syndrome
• Major resection of the stomach or small bowel
8. No uncontrolled hypertension
9. No unstable or serious concurrent condition (e.g., active infection requiring systemic therapy).
10. No poorly controlled hypertension
11. No prolongation of corrected QT interval (QTc) >480 msecs.
12. No history of any one of more of the following cardiovascular conditions within the past 6 months:
a. Cardiac angioplasty or stenting
b. Myocardial infarction
c. Unstable angina
d. Symptomatic peripheral vascular disease
e. Coronary artery by-pass graft surgery
f. Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
g. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
13. No history of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
Note: Subjects with recent DVT who have been treated with therapeutic anti-
coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible.
14. No macroscopic hematuria
15. No hemoptysis that is clinically relevant within 4 weeks of first dose of study drug.
16. No evidence of active bleeding or bleeding diathesis.
17. No known endobronchial lesions or involvement of large pulmonary vessels by tumour
18. No prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
19. No chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug.
20. No biological therapy, hormonal therapy or treatment with an investigational agent within 28 days (for bevacizumab, 60 days) or 5 half-lives, whichever is longer prior to the first dose of study drug.
21. No prohibit

Exclusion Criteria

1. Patients with recurrent sarcomas (even without prior radiotherapy) are not eligible. Ineligible sarcoma subtypes as well are: Ewing sarcoma and other PNET family tumors, rhabdomysarcomas (both pediatric and adult), osteosarcomas.
2. Patient should not be pregnant or lactating.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To study the safety and feasibility of adding 6 weeks of orally administered<br /><br>Pazopanib to 25 x 2Gy in 5 weeks preoperative radiotherapy in soft tissue<br /><br>sarcoma patients. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objective is to explore the feasibility to perform perfusion<br /><br>weighted MRI imaging regarding tumor response to RT and neoangio genesis<br /><br>inhibitor by pazopanib.</p><br>