Trial Outcomes & Findings for RAD001 and Temozolomide in Patients With Advanced Pancreatic Neuroendocrine Tumors (NCT NCT00576680)

Last Updated: 2020-07-09

Results Overview

To determine the objective response rate by RECIST criteria of RAD001 in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Partial response (PR) by these criteria is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is defined as neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

43 participants

Primary outcome timeframe

2 years

Results posted on

2020-07-09

Participant Flow

Participant milestones

Participant milestones
Measure	Temozolomide and Everolimus Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily.
Overall Study STARTED	43
Overall Study COMPLETED	43
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Temozolomide and Everolimus n=43 Participants Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily.
Age, Continuous	53 years n=43 Participants
Sex: Female, Male Female	17 Participants n=43 Participants
Sex: Female, Male Male	26 Participants n=43 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Temozolomide and Everolimus n=40 Participants Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily.
Response Rate	16 Participants

SECONDARY outcome

Timeframe: 2 years

To determine progression-free survival when RAD001 is given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors. Progression-free survival is defined as time from start of therapy until disease progression, as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, or death.

Outcome measures

Outcome measures
Measure	Temozolomide and Everolimus n=43 Participants Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily.
Progression-free Survival	15.4 months Interval 9.4 to 20.4

SECONDARY outcome

Timeframe: 2 years

To determine the safety and tolerability of RAD001 when given in combination with temozolomide in patients with advanced pancreatic neuroendocrine tumors.

Outcome measures

Outcome measures
Measure	Temozolomide and Everolimus n=43 Participants Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily.
To Determine the Safety and Tolerability of This Drug Combination. Grade 3 or 4 Lymphopenia	19 Participants
To Determine the Safety and Tolerability of This Drug Combination. Grade 3 or 4 thrombocytopenia	7 Participants
To Determine the Safety and Tolerability of This Drug Combination. Grade 3 or 4 mucositis	1 Participants
To Determine the Safety and Tolerability of This Drug Combination. Grade 3 or 4 hyperglycemia	8 Participants
To Determine the Safety and Tolerability of This Drug Combination. Grade 3 or 4 AST Increase	4 Participants
To Determine the Safety and Tolerability of This Drug Combination. Grade 3 or 4 Leukocyte decrease	7 Participants

Adverse Events

Temozolomide and Everolimus

Serious events: 15 serious events

Other events: 43 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Temozolomide and Everolimus n=43 participants at risk Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily.
Blood and lymphatic system disorders thrombocytopenia	4.7% 2/43 • Number of events 2 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Blood and lymphatic system disorders neutropenia	4.7% 2/43 • Number of events 2 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Investigations hypocalcemia	2.3% 1/43 • Number of events 1 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Renal and urinary disorders creatinine	0.00% 0/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Investigations hypophosphatemia	2.3% 1/43 • Number of events 1 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Respiratory, thoracic and mediastinal disorders pneumonitis	2.3% 1/43 • Number of events 1 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Blood and lymphatic system disorders anemia	0.00% 0/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Respiratory, thoracic and mediastinal disorders dyspnea	2.3% 1/43 • Number of events 1 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Blood and lymphatic system disorders lymphopenia	18.6% 8/43 • Number of events 10 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.

Other adverse events

Other adverse events
Measure	Temozolomide and Everolimus n=43 participants at risk Temozolomide was administered to all patients at a starting dose of 150 mg/m2 on days 1 to 7 and days 15 to 21 of a 28-day cycle. Everolimus was administered together with temozolomide in 2 dose cohorts: 1) 5 mg daily and 2) 10 mg daily.
General disorders Fatigue	76.7% 33/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Gastrointestinal disorders Nausea	76.7% 33/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Gastrointestinal disorders Mucositis	62.8% 27/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Endocrine disorders Hyperglycemia	72.1% 31/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
General disorders Hypercholesterolemia	41.9% 18/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.
Blood and lymphatic system disorders Lymphocytopenia	51.2% 22/43 • Participants were followed for development of adverse events for the entire duration while receiving treatment and for 30 days following their last dose of study treatment. Patients in this trial received a median of 8.5 four-week treatment cycles (range, 1-28). Each participant was followed for adverse events for 30 days following his or her last dose of study treatment. All-grade adverse events possible or definitely related to treatment are reported.

Additional Information

Dr. Jennifer Chan

Dana-Farber Cancer Institute

Phone: 617-632-6315

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place