Trial Outcomes & Findings for Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas (NCT NCT01048723)
NCT ID: NCT01048723
Last Updated: 2013-12-16
Results Overview
PD markers of RAD001 on downstream signaling pathways in patients with sarcomas: p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA by Western blot, quantitative multiplex assays and immunohistochemical studies measured pre and post the 2 week treatment of RAD001. Patients were to be separated into two groups, responders and non responders based on PD results and downstream up regulation of the referenced pathways. Mean fractional inhibition of each PD marker for the responding and non-responding groups were to be calculated. Our planned analysis was for 40 participants.
TERMINATED
PHASE2
2 participants
Pre and post the 2 week treatment
2013-12-16
Participant Flow
40 patients were to be treated with RAD001 in a neoadjuvant pre-resection manner 10mg po daily x 2 weeks with resection of their extremity or retroperitoneal tumors within 2 weeks after the conclusion of therapy. All patients with resectable sarcomas by CT or MRI imaging without evidence of distant metastases would be eligible for the trial.
The sarcomas must be amenable to percutaneous needle core biopsy prior to initiation of RAD001 therapy.
Participant milestones
| Measure |
RAD001 Administration
RAD001 was administered orally as once daily dose of 10 mg PO daily x 2 weeks (14 X 10 mg tablets) continuously from study day 1 until the end of therapy (2 weeks later) or unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
2
|
|
Overall Study
COMPLETED
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas
Baseline characteristics by cohort
| Measure |
RAD001 Administration
n=2 Participants
RAD001 was administered orally as once daily dose of 10 mg PO daily x 2 weeks (14 X 10 mg tablets) continuously from study day 1 until the end of therapy (2 weeks later) or unacceptable toxicity.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre and post the 2 week treatmentPD markers of RAD001 on downstream signaling pathways in patients with sarcomas: p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA by Western blot, quantitative multiplex assays and immunohistochemical studies measured pre and post the 2 week treatment of RAD001. Patients were to be separated into two groups, responders and non responders based on PD results and downstream up regulation of the referenced pathways. Mean fractional inhibition of each PD marker for the responding and non-responding groups were to be calculated. Our planned analysis was for 40 participants.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post the 2 week treatmentQuantitative in vivo and ex vivo assessments of PD markers (p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA) were to be normalized within the same sample. The extent of inhibition is defined as the fractional inhibition in each patient calculated as \[(PreRx normalized PD marker - PostRx normalized PD marker) / PreRx normalized PD marker\] x 100. Same definition would apply to each of these markers. Our planned analysis was for 40 participants.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post the 2 week treatmentWe planned to determine pathological response in terms of tumor necrosis and apoptosis assessed on the resected specimens after 2 weeks of RAD001 therapy. Percent necrosis was to be reported based on the routine H and E staining. In addition to cleaved PARP analysis, TUNEL assays were to be performed judging the amount of apoptosis in the specimens after treatment. Our planned analysis was for 40 participants.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre and Post the 2 week treatmentMemory CD8 T cell enhanced production as determined by fluorescence activated cell sorter (FACS) analysis on blood and tumor core biopsy specimens taken before and after therapy with RAD001. Our planned analysis was for 40 participants.
Outcome measures
Outcome data not reported
Adverse Events
RAD001 Administration
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
RAD001 Administration
n=2 participants at risk
RAD001 was administered orally as once daily dose of 10 mg PO daily x 2 weeks (14 X 10 mg tablets) continuously from study day 1 until the end of therapy (2 weeks later) or unacceptable toxicity.
|
|---|---|
|
Blood and lymphatic system disorders
Platelets
|
100.0%
2/2 • Number of events 2 • 1 year
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
Ear and labyrinth disorders
Tinnitus
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
General disorders
Fatigue
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Mucositis/stomatitis
|
50.0%
1/2 • Number of events 3 • 1 year
|
|
Metabolism and nutrition disorders
Creatinine
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
50.0%
1/2 • Number of events 1 • 1 year
|
Additional Information
Jonathan Zager, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place