Treatment of Patients With RAD001 With Progressive Sarcoma

Study Overview
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Brief Summary
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The purpose of this multicenter, three-arm, exact binomial single-stage, phase II trial is to determine the preliminary efficacy and safety of RAD001 in patients with histological evidence of progressive or metastatic bone or soft tissue sarcoma.

Official Title
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Multicenter, Triple-arm, Single-stage, Phase II Trial to Determine the Preliminary Efficacy and Safety of RAD001 in Patients With Histological Evidence of Progressive or Metastatic Bone or Soft Tissue Sarcomas

Conditions
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Progressive Sarcoma

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological evidence of progressive or metastatic bone or soft tissue sarcoma. The following tumor types are included: malignant fibrous histiocytoma liposarcoma synovial sarcoma malignant paraganglioma fibrosarcoma leiomyosarcoma angiosarcoma including haemangiopericytoma malignant peripheral nerve sheath tumor STS, not otherwise specified miscellaneous sarcoma including mixed mesodermal tumors of the uterus osteosarcoma Ewing's sarcoma rhabdomyosarcoma gastrointestinal stromal tumor (only after failure or intolerance of imatinib or sunitinib in 1st and 2nd line) alveolar soft part sarcoma (ASPS) Objective progression of disease may be documented by RECIST criteria. Any of the following would be sufficient according to RECIST: a 20% increase in the sum of unidimensionally measured target lesions a new lesion unequivocal increase in non-measurable disease. Patients must have disease not amenable to surgery, radiation, or combined modality therapy with curative intent. ECOG performance status 0 - 2. Exclusion Criteria: Anticancer therapy within 3 weeks of enrollment including chemotherapy, hormonal therapy, immunotherapy, or radiotherapy. The following tumor types will not be included: gastrointestinal stromal tumor (except for patients after treatment with imatinib or sunitinib in 1st and 2nd line) chondrosarcoma malignant mesothelioma neuroblastoma. Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus). Neurotoxicity > grade 2 CTC. Radiation of the lung. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Progressive or metastatic bone or soft tissue sarcomas | Drug: Everolimus<br>* 2.5 and 5 mg tablets taken orally and starting dose was 10 mg daily for all patients<br>* Other names: RAD001;|
| Experimental: Arm 2<br>Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line | Drug: Everolimus<br>* 2.5 and 5 mg tablets taken orally and starting dose was 10 mg daily for all patients<br>* Other names: RAD001;|
| Experimental: Arm 3<br>Progressive or metastatic alveolar soft part sarcoma (ASPS) | Drug: Everolimus<br>* 2.5 and 5 mg tablets taken orally and starting dose was 10 mg daily for all patients<br>* Other names: RAD001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rates by Week 16 (ITT) | The best overall response is the best response recorded from treatment start until disease progression/recurrence (both measurement and confirmation criteria). Best lesion response was defined by (Resist Criteria V1 for target and non-target lesions): Complete Response (CR)=at least two determinations of CR 4 weeks apart before progression, Partial Response (PR)=at least two determinations of CR 4 weeks apart before progression (and not qualifying for a CR), Stable Disease (SD)=at least one SD assessment >6 weeks after start of treatment and Progressive Disease (PD)=Progression or death due to underlying cancer ≤16 weeks after start of treatment. PD without radiologic evidence were classified as progression only, when clear evidence of clinical deterioration was available and patient discontinued due to disease progression. Unknown (UNK) = all other cases. | Baseline up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Rates (Complete Response and Partial Response) at Week 16 (ITT) | The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Best lesion response was defined by (Resist Criteria V1 for target and non-target lesions). | Baseline up to approximately 16 weeks | 
| Percentage of Participants With Duration of Response (CR, PR, SD) at 16 Weeks. | Duration of response (CR, PR or SD) applied only to those patients whose best overall response was CR, PR or SD based on local radiologic assessments and was defined as the time from start of treatment to progression or death from underlying disease. Patients not experiencing progression or death at 16 weeks were censored with the date of their last tumor assessment. Duration of response was explored using the Kaplan-Meier method. | Baseline up to 16 weeks | 
| Percentage of Participants With Progression-free Survival (PFS) at 16 Weeks | Progression-free Survival (PFS) was defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death from any cause. If a patient had not had an event, PFS was censored at the date of the last adequate tumor assessment at week 16 | 16 weeks | 
| Time to Progression (TTP) (ITT) | Time to progression (TTP) was defined as the time from the date of start of treatment to the date of event defined as the first documented progression or death from underlying disease. If a patient had not had an event, TTP was censored at the date of the last adequate tumor assessment, which was the date of Visit 6 (Week 16) for the core phase and the last available tumor assessment for the follow-up phase. TTP was explored by using the Kaplan-Meier method. | Baseline up to 16 weeks | 
| Percentage of Participants With Overall Survival (OS) at Week 16 (ITT) | Overall survival (OS) was defined as the time from the date of start of treatment to death from any cause. If a patient was not known to have died (was alive), OS was censored at the date of the last contact, which was the date of Visit 6 (Week 16) for the core phase and the last available visit for the follow-up phase. OS was explored by using the Kaplan-Meier method. One death occurred in Arm 3 after Week 16. | Baseline up to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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progressive GIST, progressive sarcoma