CRAD001C24114

Novartis Pharma AG

CH-4002, Basel, Switzerland,

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

No

No

No

Final

17 May 2017

No

Yes

17 May 2017

No

The primary study objective was to evaluate the preliminary efficacy of everolimus in progressive or metastatic bone and soft tissue sarcoma for each of the 3 indication arms separately. Efficacy was defined as the proportion of patients showing complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks (as best overall response) according to RECIST

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

31 Mar 2008

No

No

Germany: 61

Italy: 10

71

71

0

0

0

0

0

0

54

17

0

Overall Study (overall period)

Not applicable

Yes

everolimus

RAD001

Tablet

Oral use

The starting dose for all patients was everolimus 10 mg/day orally; this daily dose could be stepwise reduced by 2 dose levels to 5 mg/day or 5 mg every other day in the event of intolerability

everolimus

RAD001

Tablet

Oral use

The starting dose for all patients was everolimus 10 mg/day orally; this daily dose could be stepwise reduced by 2 dose levels to 5 mg/day or 5 mg every other day in the event of intolerability

everolimus

RAD001

Tablet

Oral use

The starting dose for all patients was everolimus 10 mg/day orally; this daily dose could be stepwise reduced by 2 dose levels to 5 mg/day or 5 mg every other day in the event of intolerability

Arm 1

Arm 2

Arm 3

Arm 1

Arm 2

Arm 3

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. There were no CR or PR responses.

Primary

Baseline up to 16 weeks

Arm 1 v Arm 2 v Arm 3

71

Pre-specified

40.5

2-sided

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).

Secondary

Baseline up to approximately 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. Data was rounded up. Duration of response was explored using the Kaplan-Meier method.

Secondary

Baseline up to 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. Data was rounded.

Secondary

16 weeks

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.

Secondary

Baseline up to 16 weeks

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, 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.

Secondary

Baseline up to 16 weeks

Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 16 weeks

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator

20.1

Arm I

Arm II

Arm III