IRCI Gynae Sarcomas, High Grade Uterine Sarcoma

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized Double-blind Phase II Study Evaluating the Role of Maintenance Therapy With Cabozantinib in High Grade Uterine Sarcoma (HGUtS) After Stabilization or Response to Doxorubicin +/- Ifosfamide Following Surgery or in Metastatic First Line Treatment

Conditions
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Uterine Sarcoma

Intervention / Treatment
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* Drug: Cabozantinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib<br>Cabozantinib maintenance 60 mg daily for 2 years or until withdrawal criterion After documented disease progression (according to RECIST 1.1), the treatment will be unblinded. Subjects receiving cabozantinib shall be further treated at the investigator discretion. | Drug: Cabozantinib<br> <br> |
| Experimental: Placebo<br>Placebo daily for 2 years or until withdrawal criterion. After documented disease progression (according to RECIST 1.1), the treatment will be unblinded. Subjects receiving placebo shall be offered the option of receiving cabozantinib up to further progression. This is not mandatory and treatment is at the investigator decision. | Drug: Cabozantinib<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | The primary endpoint is PFS rate at 4 months after randomization to cabozantinib or placebo | 3.5 years from first patient in | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | 3.5 years from first patient in | 
| 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 | 
| Response rate to anthracycline-based chemotherapy for the patients with measurable disease |  | 3.5 years from first patient in | 
| Assessment of global health status/QoL scale | The primary health-related quality of life endpoint that is considered of interest for this study is the global health status/QoL scale | 3.5 years from first patient in | 
| Occurence of Adverse Events | This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting. | 3.5 years from first patient in | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced, stage III, stage IV, residual disease after primary surgery, newly diagnosed HGUS, Metastatic