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
Overview
- Phase
- Phase 2
- Intervention
- Cabozantinib
- Conditions
- Uterine Sarcoma
- Sponsor
- European Organisation for Research and Treatment of Cancer - EORTC
- Enrollment
- 58
- Locations
- 14
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 9 months ago
Overview
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).
Investigators
Eligibility Criteria
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
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
Arms & Interventions
Cabozantinib
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.
Intervention: Cabozantinib
Placebo
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.
Intervention: Cabozantinib
Placebo
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: 3.5 years from first patient in
The primary endpoint is PFS rate at 4 months after randomization to cabozantinib or placebo
Secondary Outcomes
- 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(3.5 years from first patient in)
- Occurence of Adverse Events(3.5 years from first patient in)