Phase-II Study of Lu177DOTATOC in Adults With STTR(+)Pulmonary, Pheochromocytoma, Paraganglioma, Unknown Primary, Thymus NETs (PUTNET), or Any Other Non-.GEP-NET. (PUTNET)

• ClinicalTrials.gov Identifier: NCT04276597
• Recruitment Status: Withdrawn
• First Posted: February 19, 2020
• Last Update Posted: March 10, 2023
• Sponsor: Excel Diagnostics and Nuclear Oncology Center
• Information provided by (Responsible Party): Excel Diagnostics and Nuclear Oncology Center

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: 177Lu-DOTATOC	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: March 4, 2020
• Actual Primary Completion Date: July 15, 2021
• Actual Study Completion Date: July 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lu177 DOTATOC treatment; 4 doses of 200mCi 177Lu- DOTATOC PRRT	Drug: 177Lu-DOTATOC; 177Lu labeled somatostatin receptors targeting ligand

Outcome Measures

Primary Outcome Measures :

1. Assessment of the overall response rate [ Time Frame: 12 monts ]
   determined using standard of care scans NETSPOT PET/CT, Octreoscan SPECT/CT, MRI

Secondary Outcome Measures :

1. 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. [ Time Frame: 12 months ]
   determined using standard of care scans NETSPOT PET/CT, Octreoscan SPECT/CT, MRI

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

United States, Texas

Excel Diagnostics and Nuclear Oncology Center

Houston, Texas, United States, 77042

Sponsors and Collaborators

Excel Diagnostics and Nuclear Oncology Center

Investigators

• Principal Investigator: Ebrahim Delpassand, MD; Excel Diagnostics and Nuclear Oncology Center
• Study Director: Rodolfo Nunez, MD; Excel Diagnostics and Nuclear Oncology Center
• Study Director: Afshin Shafie, MD; Excel Diagnostics and Nuclear Oncology Center
• Study Director: Ayman Gaber, MD; Excel Diagnostics and Nuclear Oncology Center

More Information

• Responsible Party: Excel Diagnostics and Nuclear Oncology Center
• ClinicalTrials.gov Identifier: NCT04276597
• Other Study ID Numbers: 143631
• First Posted: February 19, 2020
• Last Update Posted: March 10, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Excel Diagnostics and Nuclear Oncology Center:

Neuroendocrine tumors; Thymus neuroendocrine; Unknown Primary; Paraganglioma; Pheochromocytoma; Pulmonary; Any other non-.GEP-NET; NET

Additional relevant MeSH terms:

Carcinoma, Merkel Cell; Carcinoma; Neoplasms; Neuroendocrine Tumors; Carcinoma, Neuroendocrine; Pheochromocytoma; Breast Neoplasms; Paraganglioma; Neoplasms, Unknown Primary; Ovarian Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Adenocarcinoma; Neoplasms by Site; Breast Diseases; Skin Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Polyomavirus Infections