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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

NCT02230176

Description:

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.

Related Conditions:
  • Pancreatic Neuroendocrine Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: 2013-004032-30
  • SECONDARY ID: 2013/2043
  • NCT ID: NCT02230176

Conditions

  • Pancreatic Neuroendocrine Carcinoma

Interventions

DrugSynonymsArms
SunitinibSunitinib
177Lu-DOTA0-Tyr3-Octreotate177Lu-DOTA0-Tyr3-Octreotate or OCLU

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
177Lu-DOTA0-Tyr3-Octreotate or OCLUExperimental7.4 GBq per injection (max: 4 injections)
  • 177Lu-DOTA0-Tyr3-Octreotate
SunitinibActive Comparator37.5 mg/day
  • Sunitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically proven and reviewed well differentiated malignant pancreatic sporadic
             NET Metastatic disease not amenable to surgical resection

          -  At least 2/3 of RECIST lesions, including measurable and non measurable lesions should
             be positive (grade of uptake at SRS ≥ 2 : equal to the liver or more) at somatostatin
             receptor scintigraphy within 24 weeks prior to enrollment.

          -  Post- first line whatever the type of systemic therapy: cytotoxic chemotherapy or
             everolimus or somatostatine analogs. In case Sandostatine LAR or Somatuline therapies
             were given for anti tumoral purpose, attempt should be made to demonstrate the
             progression under sandostatine LAR 30 mg or Somatuline LP 120 alone.

          -  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.

          -  Concomitant treatment with therapeutic doses of anticoagulants. Low dose warfarin
             (Coumadin) up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed as well
             as heparin-based anticoagulation

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To determine the 12 months PFS
Time Frame:Assessed 12 months after randomization
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:Assessed every 3 months until death
Safety Issue:
Description:
Measure:Best response
Time Frame:Assessed every 12 weeks until progression up to 48 months
Safety Issue:
Description:According to RECIST V1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gustave Roussy, Cancer Campus, Grand Paris

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