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Pazopanib Maintenance Phase II

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StatusDihentikan
Sponsor
Ludwig-Maximilians - University of Munich

Kata kunci

Abstrak

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.

tanggal

Terakhir Diverifikasi: 10/31/2017
Pertama Dikirim: 07/30/2014
Perkiraan Pendaftaran Telah Dikirim: 07/30/2014
Pertama Diposting: 08/03/2014
Pembaruan Terakhir Dikirim: 11/07/2017
Pembaruan Terakhir Diposting: 11/12/2017
Tanggal Mulai Studi Sebenarnya: 06/21/2015
Perkiraan Tanggal Penyelesaian Utama: 07/28/2016
Perkiraan Tanggal Penyelesaian Studi: 07/28/2016

Kondisi atau penyakit

Sarcoma

Intervensi / pengobatan

Drug: Pazopanib

Drug: Placebo

Tahap

Tahap 2

Kelompok Lengan

LenganIntervensi / pengobatan
Active Comparator: Pazopanib
800mg, oral, 24 months
Drug: Pazopanib
Placebo Comparator: Placebo
800mg, oral, 24 months
Drug: Placebo

Kriteria kelayakan

Usia yang Layak untuk Belajar 18 Years Untuk 18 Years
Jenis Kelamin yang Layak untuk BelajarAll
Menerima Relawan SehatIya
Kriteria

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

Hasil

Ukuran Hasil Utama

1. Progression-free Survival (PFS) [after 58 events have occurred, at the latest 27 month after the final patient is recruited]

Ukuran Hasil Sekunder

1. Overall Survival (OS) [after 58 events have occurred, at the latest 27 month after the final patient is recruited]

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