A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours

Status: Recruiting
Phase: Phase 3
Diagnosis: Gastrointestinal Malignancies
NCT ID: NCT01578239 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-282


The purpose of this study is to - compare Progression Free Survival (PFS) after treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in patients with inoperable, progressive (as determined by Response Evaluation Criteria in Solid Tumors [RECIST] Criteria), somatostatin receptor positive, well-differentiated neuroendocrine tumours of the small bowel (midgut carcinoid tumours). - compare the Objective Response Rate (ORR) between the two study arms - compare the Overall Survival (OS) between the two study arms - compare the Time to Tumour Progression (TTP) between the two study arms - evaluate the safety and tolerability of 177Lu-DOTA0-Tyr3-Octreotate - evaluate the health related quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-G.I.NET21 questionnaire - explore the correlation of toxicity outcomes and administered radiation doses corrected for body weight and body surface area - explore the correlation of clinical efficacy outcomes with the levels of the biomarkers Chromogranin-A (CgA) in the serum and 5-Hydroxyindoleacetic acid (5-HIAA) in the urine - evaluate dosimetry, pharmacokinetics (PK) and ECG in a subset of 20 patients - explore the correlation of clinical efficacy outcomes with OctreoScan® tumour uptake score - explore the correlation of clinical outcomes with serum levels of Alkaline Phosphatase (AP)


Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital

Overall PI:
Matthew Kulke, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Dana-Farber Cancer Institute: Gastrointestinal Research Line, 617-632-5960

Eligibility Criteria

Inclusion Criteria: - Presence of inoperable (curative intent) at enrolment time, histologically proven, midgut carcinoid tumour. - Ki67 index ≤ 20%. - Patients on Octreotide LAR at a fixed dose of 20 mg or 30 mg at 3-4 weeks intervals for at least 12 weeks prior to enrolment in the study. - Patients ≥18 years of age. - Patients must have progressive disease based on RECIST Criteria, Version 1.1 evidenced with CT scans/MRI within 3 years from enrolment; previous images must be centrally evaluated to confirm the disease progression under previous therapy:for the purpose of determining disease progression the oldest CT/MRI scan must not be older than 3 years and the most recent scan must not be older than 4 weeks from the projected randomization date. The CT scan/MRI scan should be one that was performed while the patient was on a fixed dose of Sandostatin LAR. - Confirmed presence of somatostatin receptors on all technically evaluable tumour lesions documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to enrolment in the study. - The tumour uptake observed using OctreoScan® must be ≥ normal liver uptake observed on planar imaging. - Karnofsky Performance Score (KPS) ≥ 60 - Presence of at least 1 measurable site of disease. Exclusion Criteria: - Serum creatinine >150 µmol/L or 1.7 mg/dL, or a measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma camera-based) of <50 mL/min. - Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x10^9/L (2000/mm3); platelets <75x10^9/L (75x10^3/mm3). - Total bilirubin >3 x upper limit of normal (ULN). - Serum albumin <3.0 g/dL unless prothrombin time is within the normal range. - Pregnancy - For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel) - Treatment with >30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to enrolment in the study. - Peptide receptor radionuclide therapy (PRRT) at any time prior to enrolment in the study. - Targeted surgery, radiotherapy (external beam), chemotherapy, embolization, interferons, mammalian target of rapamycin (mTOR)-inhibitors or other investigational therapy within 12 weeks prior to enrolment in the study. - Known 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 CT with contrast to document stable disease prior to enrolment in the study. - Uncontrolled congestive heart failure (NYHA II, III, IV). - Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 x ULN. - Any patient who has both OctreoScan® positive and negative tumours. - 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 the tumour uptake observed by OctreoScan® imaging during continued Octreotide treatment is at least as high as normal liver uptake observed by planar imaging. - Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study. - Prior external beam radiation therapy to more than 25% of the bone marrow. - Urinary incontinence. - Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years. - Patients who have not provided a signed an informed consent form to participate in the study, obtained prior to the start of any protocol related activities.
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