Pazopanib Maintenance Phase II

• Status: Terminated
• Trial end date: 2016-07-29
• Target enrollment: 0
• Participant gender: All

Summary

This trial compares pazopanib to placebo as maintenance treatment over 2 years in patients with retroperitoneal and visceral high-risk soft tissue sarcomas after multimodal treatment including prior neo- and/or adjuvant doxorubicin / ifosfamide chemotherapy with regional hyperthermia.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ludwig-Maximilians - University of Munich

Criteria

Inclusion Criteria:

• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up

• Patients must have histological evidence of high-grade soft tissue sarcoma (grade 2 - 3) according to the FNLCC grading system, tumor size ≥ 5 cm and deep localization with regard to the superficial fascia, excluding the following tumor types:

• Embryonal rhabdomyosarcoma

• Chondrosarcoma (excluding extraskeletal myxoid chondrosarcoma)

• Osteosarcoma (excluding extraskeletal osteosarcoma)

• Ewing tumors / primitive neuroectodermal tumor (PNET)

• Gastro-intestinal stromal tumors (GIST)

• Dermatofibrosarcoma protuberans

• Patients who had undergone previous surgery with inadequate margins (tumour-free margins ≤1 cm or margins contaminated) are eligible if thermochemotherapy has been started within 8 weeks after surgery

• Unstained slides and ideally tumour blocks must be available for histological central review

• Completed 4 to 8 cycles of thermochemotherapy with doxorubicin and ifosfamide at least 21 days but no more than 42 days prior to study entry

• No evidence of disease following completion of first-line thermochemotherapy and within ≤ 21 days of study entry

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• No other prior chemotherapy except thermochemotherapy with doxorubicin and ifosfamide

• Adequate organ system function

Exclusion Criteria:

• No prior or concurrent second primary malignant tumors (except adequately treated in situ carcinoma of cervix, or basal cell carcinoma)

• No symptomatic or known Central nervous system (CNS) metastases at baseline

• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

• Active peptic ulcer disease

• Known intraluminal metastatic lesion/s with risk of bleeding

• Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), 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.

• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

• Malabsorption syndrome

• Major resection of the stomach or small bowel.

• Corrected QT interval (QTc) > 480 msecs

• History of any one or more of the following cardiovascular conditions within the past 6 months:

• Cardiac angioplasty or stenting

• Myocardial infarction

• Unstable angina

• Coronary artery bypass graft surgery

• Symptomatic peripheral vascular disease

• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (See Appendix D for description)

• Poorly controlled hypertension (SBP of ≤ 150 mmHg or DBP of ≤95 mmHg is acceptable provided that BP will be treated and monitored at least weekly. The goal is to attain controlled hypertension within 4 weeks of start of IMP which is defined as grade ≤1 hypertension CTCAE Version 4.0)

• NYHA II at Screening for Patients > 65 years

• History of cerebrovascular accident including transient ischemic attack (TIA), 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-coagulating agents for at least 6 weeks are eligible

• Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).

• Evidence of active bleeding or bleeding diathesis.

• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions).

• Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.

• Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.

• Recent hemoptysis (≥½ teaspoon of red blood within 8 weeks before first dose of study drug).

• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.

• Treatment with any of the following anti-cancer therapies:

• radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR

• chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib

• Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment

• Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia