Endocrine Tumors
Conditions
Keywords
Non functioning entero-pancreatic tumours
Brief summary
The study will compare the difference between lanreotide Autogel and placebo on progression free survival in patients who have an endocrine tumour in the pancreas or intestines.
Interventions
120mg administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks.
DRUGPlacebo
Saline solution 0.9% administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks.
Sponsors
Ipsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Endocrine tumour in the intestine or pancreas and with locally advanced or metastatic disease * No hormone related symptoms * Well or moderately differentiated tumour confirmed by histology * Tumour lesions which are measurable by a CT or MRI scan
Exclusion criteria
* Previously treated with a somatostatin analogue unless more than 6 months ago and given for no more than 15 days * Treated within the last 6 months with interferon, chemoembolisation or chemotherapy or at any time with a radionuclide * Had a previous cancer except basal cell carcinoma and/or in situ carcinoma of the cervix/uterus and/or patients treated with curative intent and free from disease for 5 years * Pregnant or lactating * Females must use adequate contraception during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From randomisation up to the last tumour assessment (scheduled at 96 weeks). Radiological scans were performed every 12 weeks during the first year and every 24 weeks during the second year | Time from randomization to first documentation of disease progression, or death. Disease progression centrally assessed using Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Alive & Without Disease Progression | Week 48 & 96 | Percentage of patients still ongoing (or completing at Week 96) without centrally assessed disease progression or death at Weeks 48 and 96. |
| Pharmacokinetic Profile of Lanreotide | Week 4, 12, 24, 36, 48, 72, 96 | Pharmacokinetic Profile of Lanreotide assessed by mean serum concentration at specified timepoints |
| Change in the Global Health Status Quality of Life Assessment | Week 12 to Week 96 (last visit) | Transformed scores from European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire responses (QLQ)-C30. Questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life. |
| Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels | Week 12 to Week 96 (last visit) | — |
| Percentage of Patients Still Alive Based on Available Overall Survival Data | Randomisation to death or last visit, up to 321 weeks | Overall survival defined as the time from randomisation to death due to any cause. Subjects were followed for overall survival beyond study completion/withdrawal via annual telephone contact until the last subject completed the study. |
Countries
Austria, Belgium, Czechia, Denmark, France, Germany, India, Italy, Netherlands, Poland, Slovakia, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
264 subjects were screened at 48 investigational sites in 14 countries (Austria, Belgium, Czech Republic, Denmark, France, Germany, India, Italy, Poland, Slovakia, Spain, Sweden, United Kingdom and the United States of America). 204 subjects were randomised to receive study treatment in the Intent to treat (ITT) population.
Participants by arm
| Arm | Count |
|---|---|
| Lanreotide (Autogel Formulation) 120mg administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks. | 101 |
| Placebo Saline solution 0.9% administered via deep subcutaneous injection every 28 days for a maximum period of 96 weeks. | 103 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Not otherwise specified | 4 | 2 |
| Overall Study | Physician Decision | 6 | 9 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Placebo | Lanreotide (Autogel Formulation) | Total |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 11 | 63 years STANDARD_DEVIATION 10 | 63 years STANDARD_DEVIATION 11 |
| Chromogranin A 1-2 × ULN | 18 participants | 25 participants | 43 participants |
| Chromogranin A ≤1 × ULN | 34 participants | 33 participants | 67 participants |
| Chromogranin A >2 × ULN | 48 participants | 41 participants | 89 participants |
| Chromogranin A Unknown | 3 participants | 2 participants | 5 participants |
| Neuroendocrine tumour (NET) origin Hindgut | 3 participants | 11 participants | 14 participants |
| Neuroendocrine tumour (NET) origin Midgut | 40 participants | 33 participants | 73 participants |
| Neuroendocrine tumour (NET) origin Pancreas | 49 participants | 42 participants | 91 participants |
| Neuroendocrine tumour (NET) origin Unknown/Other | 11 participants | 15 participants | 26 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 96 Participants | 97 Participants | 193 Participants |
| Sex: Female, Male Female | 49 Participants | 48 Participants | 97 Participants |
| Sex: Female, Male Male | 54 Participants | 53 Participants | 107 Participants |
| Time since diagnosis | 34.4 months STANDARD_DEVIATION 41.4 | 32.6 months STANDARD_DEVIATION 46.1 | 33.5 months STANDARD_DEVIATION 43.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 88 / 101 | 92 / 103 |
| serious Total, serious adverse events | 25 / 101 | 32 / 103 |
Outcome results
Primary
Progression-Free Survival (PFS)
Time from randomization to first documentation of disease progression, or death. Disease progression centrally assessed using Response Evaluation Criteria in Solid Tumours (RECIST) v1.0
Time frame: From randomisation up to the last tumour assessment (scheduled at 96 weeks). Radiological scans were performed every 12 weeks during the first year and every 24 weeks during the second year
Population: Analysis based on the intent-to-treat (ITT) population which comprised 204 randomised subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lanreotide (Autogel Formulation) | Progression-Free Survival (PFS) | NA Weeks |
| Placebo | Progression-Free Survival (PFS) | 72 Weeks |
p-value: <0.00195% CI: [0.3, 0.73]Log Rank
Secondary
Change in the Global Health Status Quality of Life Assessment
Transformed scores from European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire responses (QLQ)-C30. Questionnaire response scores range from 0 to 100. Higher scores indicate best possible Quality of Life.
Time frame: Week 12 to Week 96 (last visit)
Population: Analysis based on the intent-to-treat (ITT) population which comprised 193 randomised subjects with valid assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lanreotide (Autogel Formulation) | Change in the Global Health Status Quality of Life Assessment | -5.2 score on a scale | Standard Error 3.7 |
| Placebo | Change in the Global Health Status Quality of Life Assessment | -4.9 score on a scale | Standard Error 3.7 |
Secondary
Percentage of Patients Alive & Without Disease Progression
Percentage of patients still ongoing (or completing at Week 96) without centrally assessed disease progression or death at Weeks 48 and 96.
Time frame: Week 48 & 96
Population: Analysis based on the intent-to-treat (ITT) population which comprised 204 randomised subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lanreotide (Autogel Formulation) | Percentage of Patients Alive & Without Disease Progression | Week 48 | 66 Percentage of participants |
| Lanreotide (Autogel Formulation) | Percentage of Patients Alive & Without Disease Progression | Week 96 | 53 Percentage of participants |
| Placebo | Percentage of Patients Alive & Without Disease Progression | Week 48 | 49 Percentage of participants |
| Placebo | Percentage of Patients Alive & Without Disease Progression | Week 96 | 25 Percentage of participants |
Secondary
Percentage of Patients Still Alive Based on Available Overall Survival Data
Overall survival defined as the time from randomisation to death due to any cause. Subjects were followed for overall survival beyond study completion/withdrawal via annual telephone contact until the last subject completed the study.
Time frame: Randomisation to death or last visit, up to 321 weeks
Population: Analysis based on the intent-to-treat (ITT) population which comprised 204 randomised subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanreotide (Autogel Formulation) | Percentage of Patients Still Alive Based on Available Overall Survival Data | 84 percentage of participants |
| Placebo | Percentage of Patients Still Alive Based on Available Overall Survival Data | 77 percentage of participants |
Secondary
Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels
Time frame: Week 12 to Week 96 (last visit)
Population: Analysis based on the subgroup of subjects with an elevated plasma CgA values. Subjects with a gastrinoma were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lanreotide (Autogel Formulation) | Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels | 42.2 percentage of participants |
| Placebo | Percentage of Patients With a Greater Than or Equal to 50% Decrease in Plasma Chromogranin A (CgA) Levels | 4.7 percentage of participants |
Secondary
Pharmacokinetic Profile of Lanreotide
Pharmacokinetic Profile of Lanreotide assessed by mean serum concentration at specified timepoints
Time frame: Week 4, 12, 24, 36, 48, 72, 96
Population: Analysis based on the intent-to-treat (ITT) population which comprised 101 randomised subjects who received lanreotide
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lanreotide (Autogel Formulation) | Pharmacokinetic Profile of Lanreotide | At Week 36 predose (n=67) | 6.2 ng/mL | Standard Deviation 0.39 |
| Lanreotide (Autogel Formulation) | Pharmacokinetic Profile of Lanreotide | At Week 24 predose (n=74) | 6.1 ng/mL | Standard Deviation 0.44 |
| Lanreotide (Autogel Formulation) | Pharmacokinetic Profile of Lanreotide | At Week 4 predose (n=81) | 2.5 ng/mL | Standard Deviation 0.46 |
| Lanreotide (Autogel Formulation) | Pharmacokinetic Profile of Lanreotide | At Week 12 predose (n=87) | 5.0 ng/mL | Standard Deviation 0.42 |
| Lanreotide (Autogel Formulation) | Pharmacokinetic Profile of Lanreotide | At Week 48 predose (n=62) | 6.6 ng/mL | Standard Deviation 0.45 |
| Lanreotide (Autogel Formulation) | Pharmacokinetic Profile of Lanreotide | At Week 72 predose (n=52) | 6.8 ng/mL | Standard Deviation 0.44 |
| Lanreotide (Autogel Formulation) | Pharmacokinetic Profile of Lanreotide | At Week 96 predose (n=48) | 6.6 ng/mL | Standard Deviation 0.39 |