Optimizing the Interval Between Cycles of PRRT with 177lu-dotatate in Sstr2 Positive Tumors

NCT03454763 | Active Not Recruiting Phase 2

• 1 other identifier: IRST100.26
• Study Type: interventional
• Target: 618
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized Phase II Trial in sstr2 Positive Tumors to Optimize the Interval Between Cycles of PRRT With 177lu-dotatate

Conditions

Neuroendocrine Tumors

Keywords

sst2-positive tumors; Neuroendocrine Tumors; radiolabelled somatostatin analogues (PRRT)

Outcome Measures

Primary Outcomes (2)

• PFS

  Progression free survival is defined as the time from the randomization date to the date of first observation of documented disease progression or death due to any cause

  up to 5 years

• Incidence of Treatment-Emergent Adverse Events

  The evaluation of Treatment-Emergent Adverse Events, defined as any G3/G4 toxicity from 1st treatment cycle until 30 days after the last treatment cycle will be based on version 4.0 CTC-AE

  up to 30 days after last treatment cycle

Secondary Outcomes (2)

• DCR

  up to 5 years

• OS

  up to 5 years

Study Arms (2)

Arm A, Intensive

EXPERIMENTAL

Arm A, Intensive every 5 weeks

Drug: PRRT every 5 weeks

Arm B, Non Intensive

EXPERIMENTAL

Arm B, Non Intensive every 8-10 weeks

Drug: PRRT every 8-10 weeks

Interventions

PRRT every 5 weeks DRUG

PRRT (radiolabelled somatostatin analogues) every 5 weeks for 5 cycles

Arm A, Intensive

PRRT every 8-10 weeks DRUG

PRRT (radiolabelled somatostatin analogues) every 8-10 weeks for 5 cycles

Arm B, Non Intensive

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years.
• Patients must have histologically or cytologically confirmation of neuroendocrine tumors or any other tumor histotype documented as sst2-positive), that may benefit from receptor radionuclide therapy and for which there aren't any other effective treatments. For cerebral 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..
• Measurable disease according to RECIST 1.1.criteria also patients without measurable but with evaluable disease disease can be enrolled.
• Any disease stage is allowed. Patients with documented disease will be admitted to therapeutic phase only if the diagnostic OctreoScan (the tumour uptake will be evaluated with a 3-grade scale, where 1 = liver uptake, 2 \> liver uptake and \< kidney uptake and 3 \> kidney uptake: only tumour uptakes grade 2 and 3 will be considered for therapy) and/or Positron Emission Tomography (PET)/CT 68Ga-peptide images demonstrate a significant uptake in the tumour.
• Patients with progressive disease in pre-study period (PD within the last 12 months), refractory to conventional standard treatments; clinical progression is allowed
• Patients with or without concurrent therapy with somatostatin analogs
• Life expectancy of greater than 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status =\<2
• 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 upper normal limit (UNL) , alanine aminotransferase ( ALT) and Aspartate aminotransferase (AST) \<2.5 X UNL (\< 5 X UNL in presence of liver metastases, creatinine \< 2 mg/dL.
• If female of childbearing potential highly effective birth control methods, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials", (2014\_09\_15 section 4.1) are mandatory. Highly effective birth control methods are required beginning at the screening visit and continuing until 6 months following last treatment with study drug. Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment. 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.
• Participant is willing and able to give informed consent for participation in the study.

You may not qualify if:

• Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy.
• Patients treated with previous radiometabolic therapy with an adsorbed dose to the kidney more than 23 Gy and more than 1.8 Gy for the bone marrow or as surrogate of dosimetry (13).
• Patients which are included in the indication of LUTATHERA®
• All acute toxic effects of any prior therapy (including surgery radiation therapy, chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE)
• ECOG performance status \>2
• Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
• 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.
• Assessed bone marrow invasion \> 50% (with Bone Marrow biopsy or instrumental exams i.e. bone scan or CT or MRI)
• Pregnant or breastfeeding women are excluded from the present study.

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (1)

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Meldola, FC, 47014, Italy

Location

Related Publications (3)

• Grassi I, Nicolini S, Marini I, Matteucci F, Ranallo N, Di Iorio V, Sarnelli A, Foca F, Monti M, Fabbri L, Fantini L, Rossi A, Paganelli G, Severi S, Sansovini M. Lu-PRRT Used More Intensively on Advanced Gastro-Entero-Pancreatic and Lung Neuroendocrine Neoplasms: Preliminary Results on Toxicity from a Randomized Study. Neuroendocrinology. 2025;115(5):434-445. doi: 10.1159/000542328. Epub 2024 Nov 21.

  PMID: 39571544 DERIVED

• Di Franco M, Zanoni L, Fortunati E, Fanti S, Ambrosini V. Radionuclide Theranostics in Neuroendocrine Neoplasms: An Update. Curr Oncol Rep. 2024 May;26(5):538-550. doi: 10.1007/s11912-024-01526-5. Epub 2024 Apr 6.

  PMID: 38581469 DERIVED

• Lechner M, Takahashi Y, Turri-Zanoni M, Liu J, Counsell N, Hermsen M, Kaur RP, Zhao T, Ramanathan M Jr, Schartinger VH, Emanuel O, Helman S, Varghese J, Dudas J, Riechelmann H, Sprung S, Haybaeck J, Howard D, Engel NW, Stewart S, Brooks L, Pickles JC, Jacques TS, Fenton TR, Williams L, Vaz FM, O'Flynn P, Stimpson P, Wang S, Hannan SA, Unadkat S, Hughes J, Dwivedi R, Forde CT, Randhawa P, Gane S, Joseph J, Andrews PJ, Royle G, Franchi A, Maragliano R, Battocchio S, Bewicke-Copley H, Pipinikas C, Webster A, Thirlwell C, Ho D, Teschendorff A, Zhu T, Steele CD, Pillay N, Vanhaesebroeck B, Mohyeldin A, Fernandez-Miranda J, Park KW, Le QT, West RB, Saade R, Manes RP, Omay SB, Vining EM, Judson BL, Yarbrough WG, Sansovini M, Silvia N, Grassi I, Bongiovanni A, Capper D, Schuller U, Thavaraj S, Sandison A, Surda P, Hopkins C, Ferrari M, Mattavelli D, Rampinelli V, Facchetti F, Nicolai P, Bossi P, Henriquez OA, Magliocca K, Solares CA, Wise SK, Llorente JL, Patel ZM, Nayak JV, Hwang PH, Lacy PD, Woods R, O'Neill JP, Jay A, Carnell D, Forster MD, Ishii M, London NR Jr, Bell DM, Gallia GL, Castelnuovo P, Severi S, Lund VJ, Hanna EY. Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma. Eur J Cancer. 2022 Feb;162:221-236. doi: 10.1016/j.ejca.2021.09.046. Epub 2021 Dec 31.

  PMID: 34980502 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Maddalena Sansovini, MD

  IRST IRCCS

  STUDY CHAIR

• Stefano Severi, MD

  IRST IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: comparative

Study Record Dates

• First Submitted: February 27, 2018
• First Posted: March 6, 2018
• Study Start: May 26, 2016
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

IT (1)