Uterine Sarcoma
Conditions
Keywords
Locally advanced, stage III, stage IV, residual disease after primary surgery, newly diagnosed HGUS, Metastatic
Brief summary
This study aims to investigate a drug called Cabozantinib which belongs to a family of drugs that have effects on tumour growth, blood supply, invasion and spread. Therefore, we want to find out whether taking cabozantinib after treatment with surgery and chemotherapy is effective and safe for patients who responded or had stable disease after their chemotherapy. All participants will receive 4-6 cycles of standard chemotherapy. Those with stabilization or response to the standard chemotherapy will be split into 2 groups (cabozantinib or placebo).
Interventions
DRUGCabozantinib
DRUGPlacebo
Sponsors
Gynecologic Oncology Group
NHS Greater Glasgow and Clyde
European Organisation for Research and Treatment of Cancer - EORTC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who are suitable for treatment with doxorubicin +/- ifosfamide and fall within one of the following patient populations: • HGUS, HGESS, HGLMS and HG adenosarcoma * FIGO stage II and stage III : if adjuvant chemotherapy is proposed * FIGO stage IV: if first line chemotherapy is proposed * Metastatic: diagnosed with disease relapse after local treatment for primary tumor * at least 18 years old * written informed consent * Central pathological confirmation: Histological evidence of HGUS, HGESS, HGLMS and HG adenosarcoma * Non-progressive patients (CR, PR, SD) at the end of the first line treatment (standard chemotherapy consisting of 4 to 6 cycles of anthracyclines alone or in combination with ifosfamide) * WHO/ECOG performance status 0-2 * Adequate organ and bone marrow function within 3 days prior to the first dose of study treatment (Cabozantinib/placebo) * Clinically normal cardiac function * Women of child bearing potential must have a negative serum/urine pregnancy test within 3 days prior to the first dose of study treatment * Adequate birth control measures
Exclusion criteria
* low-grade ESS, leiomyosarcoma (low or intermediate), carcinosarcoma, low-grade adenosarcoma, rhabdomyosarcoma (alveolar or embryonal) and soft tissue PNET of uterus/cervix. * contraindications to cabozantinib * not able to swallow and retain oral tablets * planned use of chemotherapy, radiation therapy, radionuclide treatment, small molecule tyrosine kinase inhibitor or hormonal therapy, and any other investigational agent (Cabozantinib/placebo) during the treatment period * concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment * patient with poorly controlled hypertension defined at baseline as blood pressure \>150/90 * patients who have suffered a cerebrovascular accident at any time in the past, patients who have suffered a transient ischemic attack in the past 6 months, patients who have suffered a deep venous thrombosis (DVT) or a pulmonary embolism in the past 6 months * Gastrointestinal disorders * patients with radiographic evidence of cavitating pulmonary lesion(s) * patients with tumor in contact with, invading or encasing any major blood vessels * patients evidence of tumor invading the GI tract * evidence of active bleeding or bleeding diathesis * hemoptysis ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment * signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment * clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment * prior major surgery or trauma within 6 weeks prior to first dose of study drug and any wound, fracture, or ulcer should be completely healed * concurrent or planned treatment with strong inhibitors or inducers of cytochrome P450 3A4/5
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 3.5 years from first patient in | The primary endpoint is PFS rate at 4 months after randomization to cabozantinib or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 3.5 years from first patient in | — |
| Response rate | 3.5 years from first patient in | — |
| Duration of response to cabozantinib | 3.5 years from first patient in | — |
| Progression free survival | 3.5 years from first patient in | — |
| Assessment of global health status/QoL scale | 3.5 years from first patient in | The primary health-related quality of life endpoint that is considered of interest for this study is the global health status/QoL scale |
| Occurence of Adverse Events | 3.5 years from first patient in | This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting. |
| Response rate to anthracycline-based chemotherapy for the patients with measurable disease | 3.5 years from first patient in | — |
Countries
France, Italy, Netherlands, Spain, United Kingdom
Outcome results
None listed