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



Status:Active, not recruiting
Conditions:Brain Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:1/12/2019
Start Date:September 2012
End Date:February 2021

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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

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)

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:

1. Presence of metastasized or locally advanced, inoperable (curative intent) at
enrollment time, histologically proven, midgut carcinoid tumour (to be centrally
confirmed).

2. Ki67 index ≤ 20% (to be centrally confirmed).

3. 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 randomization in the study.

4. Patients ≥18 years of age.

5. Patients must have progressive disease based on RECIST Criteria, Version 1.1 while
receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease
progression must be centrally confirmed. In order to make the assessment, two CT (or
MRI) scans are required. The oldest scan must not be older than 3 years from the date
of randomization. The most recent scan must not be older than 4 weeks from the date of
randomization. Both scans must be obtained while the patient is receiving the same
fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it
is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving
a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable
for either scan to be obtained before or during the time a patient receiving a fixed
dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide
for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to
the Octreotide LAR fixed dose after the OctreoScan® has been obtained.

6. Confirmed presence of somatostatin receptors on all target lesions (for
target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2,
RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive
OctreoScan® imaging within 24 weeks prior to randomization in the study (to be
centrally confirmed). The OctreoScan® should be one that was performed while the
patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan®
performed while Octreotide LAR treatment-naïve, the patient must have a repeat
OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the
clinical study to prove that the index lesions or new lesions still meet the criteria
for inclusion. It is acceptable to have patients temporarily switched to Octreotide
s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the
same fixed dose of Octreotide LAR prior to the scan.

7. The tumour uptake observed in each target lesion (for target/non-target/measurable
lesions definition see §Appendix 2, Sections 1 and 2, RECIST Criteria, Version 1.1)
using OctreoScan® must be ≥ normal liver uptake observed on planar imaging (to be
centrally confirmed) (§Appendices 5 and 6).

8. Karnofsky Performance Score (KPS)>=60.

9. Presence of at least 1 measurable site of disease.

10. [Applicable only for France] All patients included in the trial must be affiliated
with a social security regime or be a beneficiary of the same in order to be included
in the study.

Exclusion Criteria:

1. Either serum creatinine >150 µmol/L (>1.7 mg/dL), or creatinine clearance <50 mL/min
calculated by the Cockroft Gault method, eventually confirmed by measured creatinine
clearance (or measured glomerular filtration rate (GFR) using plasma clearance
methods, not gamma camera-based) <50 mL/min (the measured creatinine clearance / GFR
is required only as confirmatory exam).

2. Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L (2000/mm3); platelets <75x109/L
(75x103/mm3).

3. Total bilirubin >3 x ULN.

4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

5. Pregnancy or lactation.

6. 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) as defined in §Appendix 7.

7. Treatment with >30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to
randomization in the study.

8. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the
study.

9. Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency
ablation within 12 weeks prior to randomization in the study.

10. Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks
prior to randomization in the study.

11. Known brain metastases, unless these metastases have been treated and stabilized for
at least 24 weeks, prior to enrollment in the study. Patients with a history of brain
metastases must have a head CT with contrast to document stable disease prior to
randomization in the study.

12. Uncontrolled congestive heart failure (NYHA II, III, IV).

13. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN.

14. 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 on target lesions observed by
OctreoScan® imaging during continued Octreotide LAR treatment is at least as high as
normal liver uptake observed by planar imaging.

15. Patients with any other significant medical, psychiatric, or surgical condition,
currently uncontrolled by treatment, which may interfere with the completion of the
study.

16. Prior external beam radiation therapy to more than 25% of the bone marrow.

17. Current spontaneous urinary incontinence.

18. 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.

19. Patients who have not provided a signed informed consent form to participate in the
study, obtained prior to the start of any protocol related activities.

20. Patient with known incompatibility to CT Scans with I.V. contrast due to allergic
reaction or renal insufficiency. If such a patient can be imaged with MRI, then the
patient would not be excluded.

21. Patients who have participated in any therapeutic clinical study/received any
investigational agent within the last 30 days are excluded from participation in this
trial.
We found this trial at
14
sites
450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Chicago, Illinois 60611
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2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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Durham, NC
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1515 Holcombe Blvd
Houston, Texas 77030
 713-792-2121
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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Houston, TX
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200 Hawkins Dr,
Iowa City, Iowa 52242
866-452-8507
University of Iowa Hospitals and Clinics University of Iowa Hospitals and Clinics—recognized as one of...
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Iowa City, IA
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3535 Southern Blvd
Kettering, Ohio 45429
(937) 298-4331
Kettering Medical Center Our flagship hospital, Kettering Medical Center, stands proudly in Kettering, Ohio. From...
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Leuven,
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Nashville, Tennessee 37232
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Palo Alto, California 94304
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Philadelphia, Pennsylvania 19104
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Rochester, Minnesota 55905
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Tampa, Florida 33612
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