Peptide Receptor Radionuclide Therapy before and after Surgery for the Treatment of Metastatic, WHO Grade 1 or 2, SSTR Positive, Gastroenteropancreatic Neuroendocrine Tumor
This phase I trial learns about the feasibility and safety of using peptide receptor radionuclide therapy (PRRT) in treating patients with World Health Organization (WHO) grade 1 or 2, SSTR positive, gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have spread to other parts of the body (metastatic). PRRT treatment is based on the administration of a radioactive product, 177Lu dotatate, and its use before and after surgery is thought to increase the overall survival benefit for patients with GEP-NETs.
Inclusion Criteria
- Metastatic gastroenteropancreatic neuroendocrine tumor (GEP NET) with lymph nodes or liver metastases only
- Subjects with functional and non-functional GEP NET symptomatology are eligible (does not mean performance status)
- World Health Organization (WHO) grade 1 or 2, Ki-67 =< 20% (to be confirmed at Stanford)
- Must be a candidate for cytoreductive surgery with R1 resection as determined by a multidisciplinary tumor board discussion
- Have measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- Confirmed presence of somatostatin receptors on all target lesions as determined by 68Ga DOTATATE positron emission tomography (PET) scan (PET/computed tomography [CT] or PET/magnetic resonance imaging [MRI] are both acceptable)
- Patients >= 18 years of age
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Hemoglobin (Hgb) >= 8g/dL (>= 5.0 mmol/L) (to be done 5 to 7 days prior to treatment in case labs do not meet eligibility allows for cancellation of dose)
- White blood cells (WBC) >= 2 x 10^9/L (>= 2000/mm^3) (to be done 5 to 7 days prior to treatment in case labs do not meet eligibility allows for cancellation of dose)
- Platelets >= 75 x 10^9/L (>= 75 x 10^3/mm^3) (to be done 5 to 7 days prior to treatment in case labs do not meet eligibility allows for cancellation of dose)
- Total bilirubin < 3 x upper limit of normal (ULN) (to be done 5 to 7 days prior to treatment in case labs do not meet eligibility allows for cancellation of dose)
- Serum albumin >= 3g/dL (to be done 5 to 7 days prior to treatment in case labs do not meet eligibility allows for cancellation of dose) (EXCEPTION: prothrombin time within the normal range)
- Serum creatinine >= 1.7 mg/dL (>= 150 umol/L) OR creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockcroft Gault method (to be done 5 to 7 days prior to treatment in case labs do not meet eligibility allows for cancellation of dose)
- Fasting blood glucose < 2 x ULN (indicative of uncontrolled diabetes mellitus) (to be done 5 to 7 days prior to treatment in case labs do not meet eligibility allows for cancellation of dose)
- If patients are on a long acting somatostatin analog (SSA; such as octreotide long-acting release [LAR] or lanreotide), patients are required to be on a fixed dose for at least 12 weeks prior to study treatment administration. * Note: Concurrent SSA is not required. ** Octreotide LAR 20 mg or 30 mg is allowed at 3 to 4 weeks intervals, or ** Lanreotide 120 mg is allowed at 4 weeks intervals
Exclusion Criteria
- Prior 177Lu Dotatate treatment
- Prior radioembolization or chemoembolization
- Prior external beam radiation therapy to more than 25% of the bone marrow
- Any surgery or radiofrequency ablation within 12 weeks prior to beginning of treatment
- Any chemotherapy or targeted therapy (including everolimus and sunitinib) within 4 weeks prior to beginning of treatment
- Known history of human immunodeficiency virus (HIV)
- Pregnancy or lactation
- Female of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) or males with female partners of childbearing potential, who is not surgically sterile or in the absence of effective, non hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel)
- Known brain, bone, peritoneal metastases
- Any patient receiving treatment with short acting octreotide, which cannot be interrupted for 24 hours before and 24 hours after the administration of 177Lu Dotatate, or any patient receiving treatment with octreotide LAR, which cannot be interrupted for at least 4 weeks before the administration of 177Lu Dotatate, unless the tumor uptake on target lesions is at least as high as normal liver uptake
- Any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may pose a risk to the subject safety
- Current spontaneous urinary incontinence making impossible the safe administration of 177Lu Dotatate
- Other known co existing malignancies except non melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and with no evidence of recurrence
- Lack of a signed informed consent form to accept the study treatment
Additional locations may be listed on ClinicalTrials.gov for NCT04609592.
Locations matching your search criteria
United States
California
Palo Alto
PRIMARY OBJECTIVE:
I. To assess feasibility and safety of combination of perioperative lutetium Lu 177 dotatate (177Lu dotatate) and cytoreductive surgery in metastatic gastroenteropancreatic neuroendocrine tumors (GEP NETs).
SECONDARY OBJECTIVES:
I. To assess response rate (RR) after 2 cycles 177Lu dotatate.
II. To assess recurrence-free survival (RFS) of the overall treatment strategy.
III. To assess overall survival (OS) of the overall treatment strategy.
EXPLORATORY OBJECTIVE:
I. To determine predictive molecular biomarkers from tumor tissue, blood, cross-sectional and functional imaging.
OUTLINE:
Patients receive 177Lu dotatate intravenously (IV) over 20-30 minutes on day 1. Treatment repeats at least every 8 weeks in the absence of disease progression or unacceptable toxicity. Following 8-12 weeks after the second treatment of 177Lu dotatate, patients undergo surgery. Patients with residual disease may receive 2 additional cycles of 177Lu dotatate in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days. Patients who discontinue study treatment for a reason other than disease progression are followed every 12 weeks until disease progression or start of a new anti-cancer therapy, and then every 6 months for survival.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationStanford Cancer Institute Palo Alto
Principal InvestigatorBrendan C. Visser
- Primary IDNET0030
- Secondary IDsNCI-2021-03448
- ClinicalTrials.gov IDNCT04609592