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Treatment of Patients With RAD001 With Progressive Sarcoma

Primary Purpose

Progressive Sarcoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Everolimus
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Sarcoma focused on measuring progressive GIST, progressive sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm 3

Arm Description

Progressive or metastatic bone or soft tissue sarcomas

Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line

Progressive or metastatic alveolar soft part sarcoma (ASPS)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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.
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
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.
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.

Full Information

First Posted
October 6, 2008
Last Updated
December 31, 2018
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00767819
Brief Title
Treatment of Patients With RAD001 With Progressive Sarcoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
March 31, 2008 (Actual)
Primary Completion Date
May 17, 2017 (Actual)
Study Completion Date
May 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Sarcoma
Keywords
progressive GIST, progressive sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Progressive or metastatic bone or soft tissue sarcomas
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
Progressive gastrointestinal stromal tumors (GIST) after failure of prior imatinib and sunitinib 1st and 2nd line
Arm Title
Arm 3
Arm Type
Experimental
Arm Description
Progressive or metastatic alveolar soft part sarcoma (ASPS)
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
2.5 and 5 mg tablets taken orally and starting dose was 10 mg daily for all patients
Primary Outcome Measure Information:
Title
Best Overall Response Rates by Week 16 (ITT)
Description
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.
Time Frame
Baseline up to 16 weeks
Secondary Outcome Measure Information:
Title
Objective Tumor Response Rates (Complete Response and Partial Response) at Week 16 (ITT)
Description
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).
Time Frame
Baseline up to approximately 16 weeks
Title
Percentage of Participants With Duration of Response (CR, PR, SD) at 16 Weeks.
Description
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.
Time Frame
Baseline up to 16 weeks
Title
Percentage of Participants With Progression-free Survival (PFS) at 16 Weeks
Description
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
Time Frame
16 weeks
Title
Time to Progression (TTP) (ITT)
Description
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.
Time Frame
Baseline up to 16 weeks
Title
Percentage of Participants With Overall Survival (OS) at Week 16 (ITT)
Description
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.
Time Frame
Baseline up to 16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Bad Saarow
ZIP/Postal Code
15526
Country
Germany
Facility Name
Novartis Investigative Site
City
Duesseldorf
ZIP/Postal Code
40479
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
81377
Country
Germany
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Treatment of Patients With RAD001 With Progressive Sarcoma

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