Study to Assess the Schemas of Retreatment with Lutathera® in Patients with New Progression of Intestinal Well-Differentiated Neuroendocrine Tumor

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Regional Du Cancer De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Dec 2021 → ongoing

Decision date (initial)

2024-04-05

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCA

External identifiers

EU CT number

2024-511001-28-00

EudraCT number

2021-001306-30

ClinicalTrials.gov

NCT04954820

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance during 6 months in patients already retreated with two cycles.

Secondary objectives 4

1. To evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance during 6 months in patients already retreated with two cycles in term of Safety
2. To evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance during 6 months in patients already retreated with two cycles in term of Progression free survival (PFS)
3. To evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance during 6 months in patients already retreated with two cycles in term of Overall survival (OS)
4. To evaluate the impact of two additional cycles of Lutathera® (one injection every two months), compared to active surveillance during 6 months in patients already retreated with two cycles in term of Health quality of life (QoL) during and after treatment in both arms

Conditions and MedDRA coding

Neuroendocrine tumor

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Age ≥ 18 years
2. Histologically proven intestinal G1 or G2 neuroendocrine tumors (NET),
3. Patient previously treated with 4 cycles of Lutathera® (defined as “First PRRT”),
4. Disease control after “First PRRT” ≥ 12 months
5. Patient presenting a progression of disease (clinic, biologic and/or radiologic) after a first PRRT
6. Decision of retreatment with Lutathera® (defined as “Second PRRT”) validated by RENATEN and/or multidisciplinary tumor board and in the scope of the French reimbursement process
7. ECOG performance status 0-2
8. Life expectancy ≥ 6 months as prognosticated by the physician
9. Somatostatin receptor imaging positive imaging (SSTRi+) disease within 4 months prior to inclusion: (may be PET imaging (68Ga-based SSTR analogues) or scintigraphy imaging: 111In-pentetreotide or 99mTc-octreotide. At least 90% of lesions must be positive for SSTRi with a significant uptake (>= liver or surrounding tissue),
10. Measurable disease per RECIST 1.1 (Appendix 1), on CT/MRI scans, defined as at least 1 lesion with ≥ 1 cm in longest diameter, and ≥ 2 radiological tumors lesions in total
11. Adequate bone marrow reserve (Hb > 8 g/dl, neutrophils ≥ 1500/mm³ and platelets ≥ 80 000/mm³),
12. Negative pregnancy test in women of childbearing potential (the β-HCG dosage must be ≤ 4 days before inclusion). Women who have no reproductive potential are postmenopausal women or women who have had permanent sterilization, eg. tubal occlusion, hysterectomy, bilateral salpingectomy),
13. Effective contraception in men or women of childbearing or pre-menopausal age and up to a minimum of 7 months for female patients and 4 months for male patients following the end of treatment,
14. Patient´s signed written informed consent
15. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
16. Affiliation to the French Social Security System.

Exclusion criteria 18

1. Patient who did not respond (no CR, PR or SD) to “first PRRT”.
2. Radiological progression after two cycles of “Second PRRT” according to RECIST version 1.1
3. Grade 4 hematotoxicity and/or nephrotoxicity during the initial PRRT, or unresolved AEs categorized as Grade 2 or higher (as per Common Terminology Criteria for Adverse Events (CTCAE v5.0) from previous PRRT cycles or any other therapy for NET, excluding alopecia and peripheral neuropathy,
4. Pancreatic NET,
5. NeuroEndocrine Carcinoma,
6. Prior external beam radiation therapy to more than 25% of the bone marrow,
7. Severe renal (estimated Glomerular Filtration Rate (GFR) according to Cockcroft Gault method < 40 mL/min or nephrotic syndrome) or hepatic insufficiency (Alanine aminotransferase (ALT)/ aspartate aminotransferase (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),
8. Serum albumin < 3.0 g/dL unless prothrombin time is within the normal range,
9. Uncontrolled diabetes mellitus as defined by a fasting blood glucose above 2 ULN,
10. Uncontrolled decompensated heart failure, myocardial infarction uncontrolled, stroke, pulmonary embolism or revascularization procedure, unstable angina pectoris, uncontrolled cardiac arrhythmia, and clinically significant bradycardia during the last 12 months,
11. Hypertension that cannot be controlled despite medications (≥ 160/95 mmHg despite optimal medical therapy)
12. 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 scan with contrast or MRI to document stable disease prior to enrolment in the study),
13. Pregnancy or breast feeding
14. Substance abuse, medical, psychological, or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results,
15. Known hypersensitivity to any of the study drugs, study drug classes, or any constituent of the products,
16. Concomitant participation or participation within the last 30 days in another clinical trial,
17. History of other solid tumor in 5 years before the inclusion excepted of cancer in situ of the cervix and skin cancer (basal or squamous cell) treated and controlled.
18. Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease Control Rate (DCR) at 6 months from randomization (defined as Complete Response, Partial Response and Stable Disease from RECIST v1.1 with an evaluation every 2 months.

Secondary endpoints 5

1. The Safety according to NCI-CTCAE v5.0
2. rPFS defined as the time from randomization until documented disease progression on radiological tumor assessment (as evaluated by an independent central review by radiologists blindly of the treatment assignments according to RECIST v1.1) or death from any cause, whichever occurs first.
3. PFS defined as the time from randomization until documented disease progression on radiological tumor assessment (as evaluated by an independent central review by radiologists blindly of the treatment assignments according to RECIST v1.1) or clinical progression or death from any cause, whichever occurs first
4. OS defined as the time from randomization until death from any cause.
5. QoL assessed by EORTC QLQ-C30 and EORTC GI.NET21 questionnaires

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Regional Du Cancer De Montpellier

Sponsor organisation

Institut Regional Du Cancer De Montpellier

Address

208 Avenue Des Apothicaires

City

Montpellier Cedex 5

Postcode

34298

Country

France

Scientific contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Dr Emmanuel DESHAYES

Public contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Mme Laetitia MEIGNANT

Locations

1 EU/EEA country · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications