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A Multicentre, Stratified, Open, Randomized, Comparator-controlled, Parallel-group Phase III Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Carcinoid Tumor of the Small Bowel, Neuroendocrine Tumour

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Trial Information

A Multicentre, Stratified, Open, Randomized, Comparator-controlled, Parallel-group Phase III Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours


A multicenter, stratified, open, randomized, comparator-controlled, parallel-group phase III
study. In this study, treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care
(30 mg Octreotide LAR) will be compared to treatment with high dose (60 mg) Octreotide LAR
in patients with inoperable, somatostatin receptor positive, histologically proven midgut
carcinoid tumours; these patients should be progressive under Octreotide LAR. In case
patients in either arm experience clinical symptoms (i.e. diarrhoea and flushing) associated
with their carcinoid tumours, Octreotide s.c. rescue injections are allowed.

Objective tumour response in both arms will be assessed every 12±1 weeks from the first
treatment date according to RECIST Criteria. The baseline CT scan/MRI must not be older than
4 weeks before the projected randomization date.

Patients will be evaluated for safety and tolerability in accordance with the Visit
Schedules for the 177Lu-DOTA0-Tyr3-Octreotate arm and the Octreotide LAR arm as indicated in
Table 1 and Table 2, respectively.


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.

- Patient with known incompatibility to CT Scans with I.V. contrast due to allergic
reaction or renal insufficiency.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free survival (PFS)

Outcome Description:

Primary efficacy endpoint is PFS as measured by objective tumour response, centrally assessed according to RECIST Criteria. CT/MRI tumour assessment in both arms will be performed every 12±1 weeks from the first treatment date.

Outcome Time Frame:

12+/- 1 weeks

Safety Issue:

No

Principal Investigator

Paola Santoro, Biologist

Investigator Role:

Study Director

Investigator Affiliation:

Advanced Accelerator Applications

Authority:

United States: Food and Drug Administration

Study ID:

AAA-III-01

NCT ID:

NCT01578239

Start Date:

September 2012

Completion Date:

December 2017

Related Keywords:

  • Carcinoid Tumor of the Small Bowel
  • Neuroendocrine Tumour
  • Neuroendocrine tumour
  • 177Lu-Dota0-Tyr3-octreotate
  • Carcinoid Tumor
  • Neuroendocrine Tumors

Name

Location

MD Anderson Cancer CenterHouston, Texas  77030-4096
Mayo ClinicRochester, Minnesota  55905
Stanford University Medical CenterStanford, California  94305-5408
Vanderbilt University Medical CenterNashville, Tennessee  37232-2516
Duke UniversityDurham, North Carolina  27710
H Lee Moffitt Cancer CenterTampa, Florida  33612
Dana Farber Cancer CenterBoston, Massachusetts  02115
Cedar Sinaï Medical CenterLos Angeles, California  CA90048
Robert H Lurie Comprehensive Cancer Center of Northwestern UnivChicago, Illinois  60611-3015
University of Iowa Hospital ClinicsIowa City, Iowa  52242-1077
Oshsner Medical CenterKenner, Louisiana  70065
Weill-Cornell Medical College / New York PrebyterianNew York City, New York  10065
University of Pennsylvania Medical SchoolPhiladelphia, Pennsylvania  19104
Excel Diagnostics, Imaging ClinicHouston, Texas  77042