Receptor radionuclide therapy with 177Lu-DOTATOC (177Lu- edotreotide or 177Lu-octreotide) in SSTR positive patients: a multicenter, prospective, phase II trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-01-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519183-40-00

EudraCT number

2023-000086-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

The primary objective of this study is to evaluate the efficacy of 177Lu-DOTATOC treatment in patients affected by SSTR positive tumours.

Secondary objectives 4

1. Safety
2. Efficacy in terms of Progression Free Survival
3. Overall Survival
4. Quality of Life

Conditions and MedDRA coding

NET

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥18 years
2. Patients must have histologically or cytologically confirmation of neuroendocrine tumors or any other tumor histology type documented as sst2-positive, that may benefit from receptor radionuclide therapy and for which there are not any other effective treatments, included locoregional methods of control for PPGLs/pheochromocytoma. For cerebral and PPGLs sst2-positive tumors, if biopsy is no feasible for technical reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest oncological lesion confirming the 68Ga PET-CT dota-peptide SSTr2 positivity
3. Measurable disease according to RECIST 1.1 criteria also patients without measurable but with evaluable disease can be enrolled
4. Any disease stage is allowed. Patients with documented disease will be admitted to the therapeutic phase only if the diagnostic PET/CT 68Ga-peptide images demonstrate a significant uptake in the tumour, according to the adapted Krenning Scale. Only patients with a greater caption (Grade 3 or 4) in most of the lesions will be admitted
5. Patients with progressive disease in pre-study period (PD within the last 12 months), refractory to conventional standard treatments; clinical progression is allowed
6. Patients with or without concurrent therapy with somatostatin analogs. It will be maintained the same dose of the SSA analogs as at the time of demonstrated disease progression
7. Life expectancy of greater than 6 months
8. ECOG performance status ≤2
9. Adequate haematological, liver and renal function: haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109 /L; platelets ≥ 100 x 109 /L; bilirubin ≤1.5 X UNL (upper normal limit), ALT and AST <2.5 X UNL (< 5 X UNL in presence of liver metastases), creatinine < 2 mg/dL and/or eGFR or creatinine clearance ≥ 45 ml/min
10. A female participant is eligible to participate if she is not pregnant and not breastfeeding. If female of childbearing potential highly effective birth control methods, according to guideline “Recommendation related to contraception and pregnancy testing in clinical trials” are mandatory (see Appendix F). Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after final study drug administration. Two acceptable methods of birth control thus include Condom (barrier method of contraception) and one of the following is required ( established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg., bilateral orchiectomy), for more than 6 months
11. Participant is willing and able to give informed consent for participation in the study.

Exclusion criteria 11

1. Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy
2. Known hypersensitivity to lutetium-177 (177Lu), edotreotide, DOTA or components of the formulation or other radiolabeled peptide agents
3. Known hypersensitivity to lysine, arginine, or any excipient of the nephroprotective aminoacids given concurrently with the lutetium (177Lu) edotreotide infusion
4. Patients treated with prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow
5. Patients treated with previous PRRT with an absorbed dose to the kidney more than 23 Gy and more than 1.8 Gy for the bone marrow or as surrogate of dosimetry (13)
6. Patients which are included in the indication of LUTATHERA®
7. All acute toxic effects of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to a grade ≤ 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE)
8. ECOG performance status >2
9. Participation in another clinical trial with any investigational agents within 30 days prior to study screening
10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
11. Pregnant or breastfeeding women are excluded from the present study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is DCR, defined as the percentage of patients who have achieved complete response, partial response, stable disease (according to RECIST 1.1) at the 1st planned evaluation

Secondary endpoints 4

1. Safety was evaluated according to version 5.0 CTC-AE. Safety is defined as the percentage of patients who experience acute toxicity from the 1st treatment until 30 days after the last treatment cycle or late toxicity that occurred after 30 days from the last treatment administration up to 6 months
2. PFS is defined as the time from the start treatment date to the date of first observation of documented disease progression or death due to any cause. Patients without tumor progression at the time of analysis will be censored at their last date of tumor evaluation
3. Overall survival is defined as the time from the therapy start to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off
4. Quality of life will be evaluated through validated standardised data collection forms from the EORTC QLQ-C30 questionnaire. QoL will be collected at baseline, at every cycle of treatment start and at end of treatment

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Sponsor organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Address

Via Piero Maroncelli 40

City

Meldola

Postcode

47014

Country

Italy

Scientific contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Oriana Nanni

Public contact point

Organisation

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Contact name

Oriana Nanni

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

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

Documents 11 files

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

Application history

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