Antitumor Efficacy of Peptide Receptor Radionuclide Therapy With 177Lutetium -Octreotate Randomized vs Sunitinib in Unresectable Progressive Well-differentiated Neuroendocrine Pancreatic Tumor: First Randomized Phase II (OCCLURANDOM)
Primary Purpose
Pancreatic Neuroendocrine Carcinoma
Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Sunitinib
177Lu-DOTA0-Tyr3-Octreotate
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Neuroendocrine Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologically proven and reviewed well differentiated malignant pancreatic sporadic NET Metastatic disease not amenable to surgical resection
- All target lesions (lesions measurable and non-measurable according to the RECIST 1.1 criteria), of a size ≥ 15 mm, twice the spatial resolution of the somatostatin receptor scintigraphy (SRS), should be positive (grade of uptake at SRS≥ 2, equal to the physiologic liver uptake) within 24 weeks prior to enrollement. Negative target lesions are acceptable if below 15mm.
- Post first line whatever the type of systemic therapy: cytotoxic chemotherapy or everolimus or somatostatine analogs… Only one line of cytotoxic chemotherapy is authorized.
- Evaluable disease according to RECIST 1.1 criteria (Appendix 2)
- Progressing disease within 12 months prior to randomization according to RECIST 1.1 criteria ;
- ECOG performance status 0-2 (appendix 9)
- Life expectancy ≥ 6 months as prognosticated by the physician
- Age ≥ 18 years, no superior limit
- Adequate bone marrow reserve (Hb > 8, neutrophils ≥ 1500/mm³ and platelets ≥80.000/mm^3)
- Effective contraception in pre-menopausal female and male patients during and for at least 6 months post-treatment.
- Patient´s signed written informed consent
- Ability to comply with the protocol procedures
- Ability to take oral medication
- Patient affiliated to a social security system or beneficiary of the same.
Exclusion Criteria:
- Large or small cell-poorly differentiated pancreatic neuroendocrine tumor according to WHO 2010 classification
- Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless OctreoScan® imaging during continued Octreotide treatment is in accordance with the inclusion criteria n°2.
- More than one line of cytotoxic chemotherapy (a patient who received the same molecules of cytotoxic chemotherapy at several times during therapeutic management is considered to have benefit from one single line of cytotoxic chemotherapy)
- Prior external beam radiation therapy to more than 25% of the bone marrow
- Urinary incontinence
- History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least five years.
- Severe renal (measured GFR according to MDRD <50ml/mn or nephrotic syndrome) or hepatic insufficiency (ALT / AST > 2.5 x ULN or ALT/AST >5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin > 2.5 x ULN)
- Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
- Uncontrolled diabetes mellitus as defined by a fasting blood glucose above 2 ULN
- Decompensated heart failure (ejection fraction <45%), myocardial infarction, stroke, pulmonary embolism or revascularization procedure,unstable angina pectoris, uncontrolled cardiac arrhythmia, and clinically significant bradycardia during the last 12 months.
- Hypertension that cannot be controlled despite medications (>=160/95 mmHg despite optimal medical therapy)
- Abnormal cardiac function with 12 lead ECG. Ongoing cardiac dysrhythmias of NCI CTC grade 2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec for males or >480 msec for females.
- Brain metastases (unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrolment in the study. Patients with a history of brain metastases must have a head CTscan with contrast or MRI to document stable disease prior to enrolment in the study.)
- Pregnancy or breast feeding (see appendix 6)
- Previous treatment with the drugs under study. Prior systemic treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors.
- Current treatment with another investigational drug.
- Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days, respectively prior to study drug administration.
- Prior treatments with chemotherapy or immunotherapy or somatostatine analog therapy drug (except in case of functioning syndrome for somatostatine analogue therapy) or thoracic radiotherapy within 4 weeks prior to start of treatment
- Major surgery for any cause or local radiotherapy within one month prior to start of treatment
- Liver embolisation therapy within the last 3 months prior start of treatment except if progression is demonstrated and embolised lesion not used as targets
- Unrecovered toxicity from any kind of therapy
- Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration,or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Sites / Locations
- Gustave RoussyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
177Lu-DOTA0-Tyr3-Octreotate or OCLU
Sunitinib
Arm Description
7.4 GBq per injection (max: 4 injections)
37.5 mg/day
Outcomes
Primary Outcome Measures
To determine the 12 months PFS
Secondary Outcome Measures
Overall Survival
Best response
According to RECIST V1.1
Full Information
NCT ID
NCT02230176
First Posted
August 27, 2014
Last Updated
July 20, 2018
Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
National Cancer Institute, France, Advanced Accelerator Applications
1. Study Identification
Unique Protocol Identification Number
NCT02230176
Brief Title
Antitumor Efficacy of Peptide Receptor Radionuclide Therapy With 177Lutetium -Octreotate Randomized vs Sunitinib in Unresectable Progressive Well-differentiated Neuroendocrine Pancreatic Tumor: First Randomized Phase II
Acronym
OCCLURANDOM
Official Title
Antitumor Efficacy of Peptide Receptor Radionuclide Therapy With 177Lutetium -Octreotate Randomized vs Sunitinib in Unresectable Progressive Well-differentiated Neuroendocrine Pancreatic Tumor: First Randomized Phase II.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Unknown status
Study Start Date
February 2015 (undefined)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
National Cancer Institute, France, Advanced Accelerator Applications
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is the first randomized, open-label, national, multicenter, phase II study assessing the efficacy and safety of OCLU in subjects with pretreated progressive pancreatic, inoperable, somatostatin receptor positive, well differentiated pancreatic neuroendocrine tumors (WDpNET). Subjects must have experienced documented progression of disease within 1 year prior to the start of the study. The control group of patients receiving Sutent will be used as internal control to assess the hypothesis of 12 months PFS equal to 35% in patients receiving Sutent.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neuroendocrine Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
177Lu-DOTA0-Tyr3-Octreotate or OCLU
Arm Type
Experimental
Arm Description
7.4 GBq per injection (max: 4 injections)
Arm Title
Sunitinib
Arm Type
Active Comparator
Arm Description
37.5 mg/day
Intervention Type
Drug
Intervention Name(s)
Sunitinib
Intervention Type
Drug
Intervention Name(s)
177Lu-DOTA0-Tyr3-Octreotate
Primary Outcome Measure Information:
Title
To determine the 12 months PFS
Time Frame
Assessed 12 months after randomization
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
Assessed every 3 months until death
Title
Best response
Description
According to RECIST V1.1
Time Frame
Assessed every 12 weeks until progression up to 48 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven and reviewed well differentiated malignant pancreatic sporadic NET Metastatic disease not amenable to surgical resection
All target lesions (lesions measurable and non-measurable according to the RECIST 1.1 criteria), of a size ≥ 15 mm, twice the spatial resolution of the somatostatin receptor scintigraphy (SRS), should be positive (grade of uptake at SRS≥ 2, equal to the physiologic liver uptake) within 24 weeks prior to enrollement. Negative target lesions are acceptable if below 15mm.
Post first line whatever the type of systemic therapy: cytotoxic chemotherapy or everolimus or somatostatine analogs… Only one line of cytotoxic chemotherapy is authorized.
Evaluable disease according to RECIST 1.1 criteria (Appendix 2)
Progressing disease within 12 months prior to randomization according to RECIST 1.1 criteria ;
ECOG performance status 0-2 (appendix 9)
Life expectancy ≥ 6 months as prognosticated by the physician
Age ≥ 18 years, no superior limit
Adequate bone marrow reserve (Hb > 8, neutrophils ≥ 1500/mm³ and platelets ≥80.000/mm^3)
Effective contraception in pre-menopausal female and male patients during and for at least 6 months post-treatment.
Patient´s signed written informed consent
Ability to comply with the protocol procedures
Ability to take oral medication
Patient affiliated to a social security system or beneficiary of the same.
Exclusion Criteria:
Large or small cell-poorly differentiated pancreatic neuroendocrine tumor according to WHO 2010 classification
Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless OctreoScan® imaging during continued Octreotide treatment is in accordance with the inclusion criteria n°2.
More than one line of cytotoxic chemotherapy (a patient who received the same molecules of cytotoxic chemotherapy at several times during therapeutic management is considered to have benefit from one single line of cytotoxic chemotherapy)
Prior external beam radiation therapy to more than 25% of the bone marrow
Urinary incontinence
History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least five years.
Severe renal (measured GFR according to MDRD <50ml/mn or nephrotic syndrome) or hepatic insufficiency (ALT / AST > 2.5 x ULN or ALT/AST >5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin > 2.5 x ULN)
Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
Uncontrolled diabetes mellitus as defined by a fasting blood glucose above 2 ULN
Decompensated heart failure (ejection fraction <45%), myocardial infarction, stroke, pulmonary embolism or revascularization procedure,unstable angina pectoris, uncontrolled cardiac arrhythmia, and clinically significant bradycardia during the last 12 months.
Hypertension that cannot be controlled despite medications (>=160/95 mmHg despite optimal medical therapy)
Abnormal cardiac function with 12 lead ECG. Ongoing cardiac dysrhythmias of NCI CTC grade 2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec for males or >480 msec for females.
Brain metastases (unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrolment in the study. Patients with a history of brain metastases must have a head CTscan with contrast or MRI to document stable disease prior to enrolment in the study.)
Pregnancy or breast feeding (see appendix 6)
Previous treatment with the drugs under study. Prior systemic treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors.
Current treatment with another investigational drug.
Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days, respectively prior to study drug administration.
Prior treatments with chemotherapy or immunotherapy or somatostatine analog therapy drug (except in case of functioning syndrome for somatostatine analogue therapy) or thoracic radiotherapy within 4 weeks prior to start of treatment
Major surgery for any cause or local radiotherapy within one month prior to start of treatment
Liver embolisation therapy within the last 3 months prior start of treatment except if progression is demonstrated and embolised lesion not used as targets
Unrecovered toxicity from any kind of therapy
Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration,or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eric BAUDIN, MD, PhD
Phone
0142114244
Ext
+33
Email
eric.baudin@gustaveroussy.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Agnès LAPLANCHE, MD
Phone
0142114127
Ext
+33
Email
agnes.laplanche@gustaveroussy.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric BAUDIN, MD
Organizational Affiliation
Gustave Roussy, Cancer Campus, Grand Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gustave Roussy
City
Villejuif
State/Province
Val De Marne
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa LAMBERT
Phone
0142116643
Ext
+33
Email
lisa.lambert@gustaveroussy.fr
First Name & Middle Initial & Last Name & Degree
Eric BAUDIN, MD, PhD
12. IPD Sharing Statement
Learn more about this trial
Antitumor Efficacy of Peptide Receptor Radionuclide Therapy With 177Lutetium -Octreotate Randomized vs Sunitinib in Unresectable Progressive Well-differentiated Neuroendocrine Pancreatic Tumor: First Randomized Phase II
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