Sarcoma
Conditions
Keywords
high-risk soft tissue sarcoma, pazopanib, retroperitoneal soft tissue sarcoma, visceral soft tissue sarcoma, votrient
Brief 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.
Interventions
DRUGPazopanib
DRUGPlacebo (for Pazopanib)
Sponsors
Ludwig-Maximilians - University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Study Start Dat: June 22, 2015; Study Completion Date: July 29, 2016 ; an approximate study duration of 13 months | The study could not be evaluated. Only one patient was included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Study Start Dat: June 22, 2015; Study Completion Date: July 29, 2016 ; an approximate study duration of 13 months | The study could not be evaluated. Only one patient was included. |
Countries
Germany
Participant flow
Recruitment details
Targeted recruitment goal were 150 patients, 1 patient was randomised
Pre-assignment details
Contrary to the original expectation, patients with retroperitoneal or visceral high-risk soft tissue sarcoma were generally not prepared to undergo further therapy with pazopanib for 2 years after multimodal therapy consisting of 8 cycles of chemotherapy in combination with hyperthermia, surgery and, if necessary, radiotherapy, which may have side effects.
Participants by arm
| Arm | Count |
|---|---|
| Pazopanib 800mg, oral, 24 months
Pazopanib | 1 |
| Placebo 800mg, oral, 24 months
Placebo (for Pazopanib) | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Pazopanib | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Region of Enrollment Germany | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Progression-free Survival (PFS)
The study could not be evaluated. Only one patient was included.
Time frame: Study Start Dat: June 22, 2015; Study Completion Date: July 29, 2016 ; an approximate study duration of 13 months
Population: The study could not be evaluated. Only one patient was included.~Contrary to the original expectation, patients with retroperitoneal or visceral high-risk soft tissue sarcoma were generally not prepared to undergo further therapy with pazopanib for 2 years after multimodal therapy consisting of 8 cycles of chemotherapy in combination with hyperthermia, surgery and, if necessary, radiotherapy, which may have side effects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pazopanib | Progression-free Survival (PFS) | 1 Participants |
| Placebo | Progression-free Survival (PFS) | 0 Participants |
Secondary
Overall Survival (OS)
The study could not be evaluated. Only one patient was included.
Time frame: Study Start Dat: June 22, 2015; Study Completion Date: July 29, 2016 ; an approximate study duration of 13 months