Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET. (PUTNET)
Primary Purpose
Pulmonary Neuroendocrine Neoplasm, Pheochromocytoma, Paraganglioma
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
177Lu-DOTATOC
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Neuroendocrine Neoplasm focused on measuring Neuroendocrine tumors, Thymus neuroendocrine, Unknown Primary, Paraganglioma, Pheochromocytoma, Pulmonary, Any other non-.GEP-NET, NET
Eligibility Criteria
Inclusion criteria:
- Signed informed consent.
- Subjects of either sex, aged ≥18 years.
- ECOG status 0-2.
- Life-expectancy of at least 12 weeks.
- Histologically/cytologically confirmed diagnosis of SSTR (+) neuroendocrine tumors of the lung, Pheochromocytoma, Paraganglioma, thymus, and unknown primary, unresectable or metastatic.
- Measurable disease per RECIST 1.1, on CT/MRI scans, defined as at least 1 lesion with ≥ 1 cm in longest diameter (lymph nodes along short axis >15 mm).
- Appropriate diagnostic imaging studies, at the discretion of the P.I. including but not limited to CT, MRI , 18F-FDG PET/CT, NAF PET/CT bone scan, ultrasound, etc. of the tumor region or suspected area within the 4 weeks of dosing day.
- Somatostatin receptor positive (SSTR+) disease, as evidenced by available FDA, commercially of IND approved SSTR imaging (SRI), within 4 weeks prior to the first cycle
- Recent blood test results (within 2weeks pre-dose) as follows:
- Sufficient bone marrow capacity as defined by WBC ≥2,500/µl and WBC≥2,000/mm3 for subsequent cycles; platelets ≥ 100,000 (100 * 103/mm3) for the first treatment and ≥75,000 for the subsequent therapies, Hgb ≥8.9 g/dl for the first treatment and 8.0 g/dl for the subsequent therapies, ANC ≥1500/mm3 for the first treatment and ≥1000/ mm3; for the subsequent therapies.
- ALT, AST values ≤3 times ULN
- Bilirubin: ≤3 times ULN
- Serum creatinine ≤ 150 µmol/liter or 1.7 mg/dl
- Negative pregnancy test in women capable of child-bearing within 48 hours of IMP administration.
- Serum albumin > 3.0g/L (<3 g/L may be acceptable at the discretion of investigator, if PT, PTT, and INR are within normal range)
- All available FDA-approved therapies for which the subject is eligible have been exhausted (with the exception of PRRT), unless available therapies are refused by the subject (with the exception of somatostatin analogue, octreotide, and somatuline).
Exclusion Criteria:
- Known hypersensitivity to any of the excipients of Lu-177 DOTATOC.
- Therapeutic use of any somatostatin analogue, including Sandostatin® LAR (within 28 days) and Sandostatin® (within 1 day) prior to treatment.
- Subjects with unusual hematological parameters, including an increased MCV (>105fL), and especially in those who had previous chemotherapy, the advice of a hematologist should be sought for adequate further work-up
- Any subject who is taking concomitant medications that decrease renal function (such as aminoglycoside antibiotics).
- Female subjects who are pregnant, lactating or women of childbearing potential not willing to practice effective contraceptive techniques during the study period and for 67 days (more than 10 half-lives of 177Lu after the last treatment, or male subjects who have female partners of childbearing potential not willing to practice abstinence or effective contraception, during the study period and for 67 days after the last treatment.
- Current somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study.
- Indication for surgical lesion removal with curative potential
- Planned (for the period of study participation): chemotherapy, immunotherapy, radiation therapy (unless regional for pain relief) chemo-embolization, bland embolization, radio-embolization, treatment with cyclosporine-A.
- Known brain metastases; unless these metastases have been treated and stabilized 6 months prior to enrolment
- Completion of: (1) cytotoxic chemotherapy for less than 6 weeks; (2) a biological agent for less than 5 half-lives; and (3) radiation therapy (except regional for pain relief) for less than 6 weeks prior to study enrolment,
- Uncontrolled congestive heart failure; subjects suspected of having this condition need to show ejection fraction of > 35% as determined by MUGA scan.
- Glomerular Filtration Rate (GFR) < 35 mL/min
- Subjects with prior peptide receptor radionuclide therapy (PPRT).
Sites / Locations
- Excel Diagnostics and Nuclear Oncology Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lu177 DOTATOC treatment
Arm Description
4 doses of 200mCi 177Lu- DOTATOC PRRT
Outcomes
Primary Outcome Measures
Assessment of the overall response rate
determined using standard of care scans NETSPOT PET/CT, Octreoscan SPECT/CT, MRI
Secondary Outcome Measures
Progression Free Survival (rPFS) in subjects receiving 4 cycles of therapy Monitoring of the changes in quality of life (QOL) through assessment of ECOG performance status and a QOL subject questionnaire.
determined using standard of care scans NETSPOT PET/CT, Octreoscan SPECT/CT, MRI
Full Information
NCT ID
NCT04276597
First Posted
February 14, 2020
Last Updated
March 9, 2023
Sponsor
Excel Diagnostics and Nuclear Oncology Center
1. Study Identification
Unique Protocol Identification Number
NCT04276597
Brief Title
Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET.
Acronym
PUTNET
Official Title
A Phase II, Non-Randomized, Open-Label, Single-center, Physician Sponsored Study to Determine the Safety and Effectiveness of Lu-177 DOTATOC in Adult Subjects With Somatostatin Receptor Expressing Pulmonary, Pheochromocytoma, paragangliomUnknown Primary, and Thymus Neuroendocrine Tumors (PUTNET) or Any Other Non-.GEP-NET.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Withdrawn
Why Stopped
No subjects were eligible for the study. The study closed on 07-15-2021.
Study Start Date
March 4, 2020 (Actual)
Primary Completion Date
July 15, 2021 (Actual)
Study Completion Date
July 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Excel Diagnostics and Nuclear Oncology Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Determine the safety and effectiveness of Lu-177 DOTATOC in adult subjects with somatostatin receptor-expressing Pulmonary, Pheochromocytoma, Paraganglioma, Unknown primary, and Thymus neuroendocrine tumors or any other non-.GEP-NET.
The treatment regimen will consist of 4 doses of 200 (±10%) mCi 177Lu-DOTATOC administered at 8+/- 1-week intervals.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Neuroendocrine Neoplasm, Pheochromocytoma, Paraganglioma, Thymus Carcinoid, Unknown Primary Tumors, Neuroendocrine Tumors, Neuroendocrine Skin Carcinoma, Neuroendocrine Breast Tumor, Neuroendocrine Carcinoma Metastatic, Neuroendocrine Neoplasm of Ovary
Keywords
Neuroendocrine tumors, Thymus neuroendocrine, Unknown Primary, Paraganglioma, Pheochromocytoma, Pulmonary, Any other non-.GEP-NET, NET
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lu177 DOTATOC treatment
Arm Type
Experimental
Arm Description
4 doses of 200mCi 177Lu- DOTATOC PRRT
Intervention Type
Drug
Intervention Name(s)
177Lu-DOTATOC
Intervention Description
177Lu labeled somatostatin receptors targeting ligand
Primary Outcome Measure Information:
Title
Assessment of the overall response rate
Description
determined using standard of care scans NETSPOT PET/CT, Octreoscan SPECT/CT, MRI
Time Frame
12 monts
Secondary Outcome Measure Information:
Title
Progression Free Survival (rPFS) in subjects receiving 4 cycles of therapy Monitoring of the changes in quality of life (QOL) through assessment of ECOG performance status and a QOL subject questionnaire.
Description
determined using standard of care scans NETSPOT PET/CT, Octreoscan SPECT/CT, MRI
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Signed informed consent.
Subjects of either sex, aged ≥18 years.
ECOG status 0-2.
Life-expectancy of at least 12 weeks.
Histologically/cytologically confirmed diagnosis of SSTR (+) neuroendocrine tumors of the lung, Pheochromocytoma, Paraganglioma, thymus, and unknown primary, unresectable or metastatic.
Measurable disease per RECIST 1.1, on CT/MRI scans, defined as at least 1 lesion with ≥ 1 cm in longest diameter (lymph nodes along short axis >15 mm).
Appropriate diagnostic imaging studies, at the discretion of the P.I. including but not limited to CT, MRI , 18F-FDG PET/CT, NAF PET/CT bone scan, ultrasound, etc. of the tumor region or suspected area within the 4 weeks of dosing day.
Somatostatin receptor positive (SSTR+) disease, as evidenced by available FDA, commercially of IND approved SSTR imaging (SRI), within 4 weeks prior to the first cycle
Recent blood test results (within 2weeks pre-dose) as follows:
Sufficient bone marrow capacity as defined by WBC ≥2,500/µl and WBC≥2,000/mm3 for subsequent cycles; platelets ≥ 100,000 (100 * 103/mm3) for the first treatment and ≥75,000 for the subsequent therapies, Hgb ≥8.9 g/dl for the first treatment and 8.0 g/dl for the subsequent therapies, ANC ≥1500/mm3 for the first treatment and ≥1000/ mm3; for the subsequent therapies.
ALT, AST values ≤3 times ULN
Bilirubin: ≤3 times ULN
Serum creatinine ≤ 150 µmol/liter or 1.7 mg/dl
Negative pregnancy test in women capable of child-bearing within 48 hours of IMP administration.
Serum albumin > 3.0g/L (<3 g/L may be acceptable at the discretion of investigator, if PT, PTT, and INR are within normal range)
All available FDA-approved therapies for which the subject is eligible have been exhausted (with the exception of PRRT), unless available therapies are refused by the subject (with the exception of somatostatin analogue, octreotide, and somatuline).
Exclusion Criteria:
Known hypersensitivity to any of the excipients of Lu-177 DOTATOC.
Therapeutic use of any somatostatin analogue, including Sandostatin® LAR (within 28 days) and Sandostatin® (within 1 day) prior to treatment.
Subjects with unusual hematological parameters, including an increased MCV (>105fL), and especially in those who had previous chemotherapy, the advice of a hematologist should be sought for adequate further work-up
Any subject who is taking concomitant medications that decrease renal function (such as aminoglycoside antibiotics).
Female subjects who are pregnant, lactating or women of childbearing potential not willing to practice effective contraceptive techniques during the study period and for 67 days (more than 10 half-lives of 177Lu after the last treatment, or male subjects who have female partners of childbearing potential not willing to practice abstinence or effective contraception, during the study period and for 67 days after the last treatment.
Current somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study.
Indication for surgical lesion removal with curative potential
Planned (for the period of study participation): chemotherapy, immunotherapy, radiation therapy (unless regional for pain relief) chemo-embolization, bland embolization, radio-embolization, treatment with cyclosporine-A.
Known brain metastases; unless these metastases have been treated and stabilized 6 months prior to enrolment
Completion of: (1) cytotoxic chemotherapy for less than 6 weeks; (2) a biological agent for less than 5 half-lives; and (3) radiation therapy (except regional for pain relief) for less than 6 weeks prior to study enrolment,
Uncontrolled congestive heart failure; subjects suspected of having this condition need to show ejection fraction of > 35% as determined by MUGA scan.
Glomerular Filtration Rate (GFR) < 35 mL/min
Subjects with prior peptide receptor radionuclide therapy (PPRT).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ebrahim Delpassand, MD
Organizational Affiliation
Excel Diagnostics and Nuclear Oncology Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rodolfo Nunez, MD
Organizational Affiliation
Excel Diagnostics and Nuclear Oncology Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Afshin Shafie, MD
Organizational Affiliation
Excel Diagnostics and Nuclear Oncology Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ayman Gaber, MD
Organizational Affiliation
Excel Diagnostics and Nuclear Oncology Center
Official's Role
Study Director
Facility Information:
Facility Name
Excel Diagnostics and Nuclear Oncology Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77042
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET.
We'll reach out to this number within 24 hrs