IRCI Gynae Sarcomas, High Grade Uterine Sarcoma

Prior treatment

• 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
• 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

Other illness

• 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
• evidence of active bleeding or bleeding diathesis

Other

• 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
• 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

• 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