Clinical Study of Concurrent Pazopanib and Radiotherapy for Non-metastatic Sarcoma Patients

NCT02575066 | Terminated Phase 2 DMC

• 2 other identifiers: M15PASDSSG02
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 3

Brief Summary

Radiotherapy (RT) alone is able to induce a clinically significant effect with a variable pathologic response (a pathological complete remission, pCR, defined as ≥ 95%, or ≤ 5% remaining visible tumour cells) in only about 10% of cases. A prior phase I study (PASART-1; NCT01985295) suggested that 25 x 2 Gy preoperative RT in combination with once daily 800mg oral pazopanib is feasible, while inducing tissue replacing tumor that can consist of fibrosis and necrosis in 40% of thus treated patients. During this study, the interim analysis showed that the combination treatment of preoperative radiation with orally pazopanib is more effective than was anticipated. For this reason, the pazopanib dose of 800 mg once daily is maintained but the RT dose is reduced to 18x2Gy instead of 25x2Gy. Predominant aim of this RT dose reduction is lowering the wound complication risk after preoperative radiotherapy.

Conditions

Sarcoma; Soft Tissue Sarcomas

Keywords

pazopanib; radiotherapy

Outcome Measures

Primary Outcomes (1)

• pathological near complete remission of the resected specimen which has been treated with radiotherapy

  Proportion of patients with resection specimens demonstrating induction of a pathological (near) complete remission (≥ 95% tumor regression). Pathological (near) complete remission is defined as ≥ 95% replacement of tumor with other tissue, usually fibrosis and) in the resection specimen post combined pazopanib and radiotherapy treatment

  6 weeks post treatment

Secondary Outcomes (3)

• Incidence toxicities measured by NCI-CTCAE v4.0 (radiotherapy alone, pazopanib alone or both) measured from start of treatment until 6 weeks post-treatment

  during treatment and up to 6 weeks post treatment

• Rate of response as measured by RECIST v 1.1 at 4 weeks after completing radiotherapy

  4 weeks post treatment

• Incidence of acute post-operative wound complications up to 3 weeks (+/- 1 week) after surgery as defined in section 6.1.3 and reference 29 (see also appendix XII)

  up to 3 weeks post surgery

Study Arms (1)

radiotherapy combined with pazopanib

OTHER

patients during the first part of the study received concurrent radiotherapy (25x2Gy) and pazopanib (QD 800 mg). The patients of the second part of the study will receive concurrent radiotherapy (18x2Gy) and pazopanib (QD 800 mg).

Radiation: external beam radiotherapy; Drug: pazopanib

Interventions

external beam radiotherapy RADIATION

external beam radiotherapy 25 x 2 Gy / 18 x 2 Gy

Also known as: radiotherapy

radiotherapy combined with pazopanib

pazopanib DRUG

pazopanib QD 800 mg

radiotherapy combined with 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 newly diagnosed intermediate to high grade soft tissue sarcoma localized to the extremities, trunk and chest wall or the head and neck area, for which the standard treatment is a combination of and radiotherapy and surgery(deep seated and/or \> 5cm according to the RECIST 1.1 criteria and/or an anticipated close resection margin and/or grade II/III according to the WHO definition)
• Age ≥ 18 years
• WHO performance status of ≤ 1
• Able and willing to undergo blood sampling for PK and PD analysis
• Able to swallow and retain oral medication
• Able and willing to undergo MRI scanning
• Able and willing to undergo tumor biopsies
• Adequate organ functions as described by the laboratory findings in the table 1. For thyroid function, the T4 and TSH values must be within normal values of the range of the participating centers
• Written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.

You may not qualify if:

• Prior malignancies; except another malignancy and disease-free for ≥ 5 years, or completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
• Patients with recurrent sarcomas (even without prior radiotherapy)
• Ewing sarcoma and other PNET family tumors, rhabdomyosarcomas (both pediatric and adult), osteosarcomas
• Clinically significant gastrointestinal abnormalities which might interfere with oral dosing diagnosed
• Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\]
• Unstable or serious concurrent condition (e.g., active infection requiring systemic therapy)
• Prolongation of corrected QT interval (QTc) \> 480 msecs on ECG
• History of any of more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Symptomatic peripheral vascular disease
• Coronary artery by-pass graft surgery
• Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA)
• History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Royal Marsden NHS Foundation Trust: collaborator

Study Sites (3)

Antoni van Leeuwenhoek

Amsterdam, 1066CX, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Radiotherapy; pazopanib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Rick Haas, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

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: September 16, 2015
• First Posted: October 14, 2015
• Study Start: March 17, 2016
• Primary Completion: March 20, 2019
• Study Completion: March 20, 2019
• Last Updated: June 27, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); GB (1)