Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET

NCT06784752 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CAAA601A623012024-518325-15-00
• Study Type: interventional
• Target: 240
• Locations: 12 countries
• Sites: 65

Brief Summary

The purpose of the current study is to evaluate the efficacy and safety of \[177Lu\]Lu-DOTA-TATE plus octreotide long-acting release (LAR) versus octreotide LAR alone in newly diagnosed patients with somatostatin receptor positive (SSTR+), well differentiated Grade1 and Grade 2 (G1 and G2) (Ki-67 \<10%) advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with high disease burden

Conditions

Somatostatin Receptor Positive (SSTR+); Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET)

Keywords

SSTR+; GEP-NET; Ki-67 <10%; AAA601; [177Lu]Lu-DOTA-TATE; newly diagnosed; well differentiated; advanced GEP-NETs; high disease burden; NETTER-3; Grade 1; Grade 2; Tumor-targeted radioligand therapy; RLT; octreotide LAR; Gastroenteropancreatice Neuroendocrine Tumor; PFS; Quality of life (QOL)/PRO; QoL; neuroendocrine tumor(s); Lutathera; Lutetium dotatate; Lutetium oxodotreotide

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) centrally assessed by Blinded Independent Review Committee (BIRC)

  PFS is defined as the time from randomization to the first occurrence of progression (centrally assessed by Blinded Independent Review Committee (BIRC) according to RECIST v1.1) or death due to any cause.

  After observing approximately 88 PFS events as per BIRC assessments, expected after approximately 33 months from study start

Secondary Outcomes (15)

• Time to Deterioration (TDD) (Key Secondary)

  After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start

• Progression Free Survival (PFS)

  After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start

• Objective Response Rate (ORR)

  After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start

• Disease Control Rate (DCR)

  After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start

• Duration of Response (DOR)

  After observing approximately 88 PFS events as per BIRC assessment, expected after approximately 33 months from study start

Study Arms (2)

[177Lu]Lu-DOTA-TATE + Octreotide LAR

EXPERIMENTAL

Participants in this arm will receive \[177Lu\]Lu-DOTA-TATE plus Octreotide long-acting release (LAR).

Radiation: [177Lu]Lu-DOTA-TATE; Drug: Octreotide LAR

Octreotide LAR

ACTIVE COMPARATOR

Participants in this arm will receive Octreotide LAR only.

Drug: Octreotide LAR

Interventions

[177Lu]Lu-DOTA-TATE RADIATION

\[177Lu\]Lu-DOTA-TATE will be administered 4 times during treatment period with frequency of every 8 weeks (Q8W)

[177Lu]Lu-DOTA-TATE + Octreotide LAR

Octreotide LAR DRUG

Octreotide LAR will be administered Q8W when co-administered with \[177Lu\]Lu-DOTA-TATE in the investigational arm followed by Q4W. In the control arm Octreotide LAR will be administered Q4W.

Also known as: SOM230

Octreotide LAR; [177Lu]Lu-DOTA-TATE + Octreotide LAR

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of metastasized or locally advanced, unresectable (curative intent), histologically proven, well differentiated Grade 1 or Grade 2 (Ki-67 \<10%) gastroenteropancreatic neuroendocrine tumor (GEP-NET) diagnosed within 6 months prior to screening.
• Participants with high disease burden in the Investigator's opinion. Following criteria should be used as the guiding principle for determining high disease burden:
• Primary tumor or a metastatic lesion \> 4 cm
• More than one tumor or metastatic lesions measuring \> 2 cm
• Elevated alkaline phosphatase \> 2.5 X upper limit of normal (ULN)
• Presence of bone metastasis
• Presence of peritoneal metastasis
• Symptoms due to tumor volume such as pain, fatigue, weight loss, anorexia etc.
• Symptoms due to hormone excess requiring active management
• Additionally, participants who, in the Investigator's opinion, have high disease burden due to their disease characteristics not specified above could also be considered eligible.
• Participants ≥ 12 years of age.
• RLI somatostatin receptor (SSTR) uptake on all target lesions (defined by RECIST v1.1 criteria) at least as high as normal liver uptake assessed within 3 months prior to randomization. Any of the RLI modalities as available (some examples are listed below) can be used as per local practice:
• \[68Ga\]Ga-DOTA-TOC PET/CT or PET/MRI
• \[68Ga\]Ga-DOTA-TATE PET/CT or PET/MRI
• \[64Cu\]Cu-DOTA-TATE PET/CT or PET/MRI

You may not qualify if:

• Prior administration of a therapeutic radiopharmaceutical for GEP-NET at any time prior to randomization in the study.
• Any previous therapy with interferons, mTOR-inhibitors, chemotherapy or other systemic therapies except somatostatin analogues (SSAs) of GEP-NET. If as per Investigator's opinion a participant is candidate for such therapies, such participant must not be enrolled.
• Participant who received more than 4 cycles of prior SSAs (e.g., octreotide long-acting release) are not eligible. In addition, any participant receiving treatment with short-acting octreotide, which cannot be interrupted for 24 h before the administration of \[177Lu\]Lu-DOTA-TATE, or any participant receiving treatment with SSAs, which cannot be interrupted for at least 4 weeks before the administration of \[177Lu\]Lu-DOTA-TATE.
• Documented RECIST v1.1 progression during previous SSA treatments for the current GEP-NET at any time prior to randomization.
• Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET.
• Any major surgery within 12 weeks prior to randomization in the study.
• Known brain metastases.
• Participant with known intolerance to CT scans with intravenous (i.v.) contrast due to allergic reaction or renal insufficiency. If such a participant can be imaged with MRI, then the participant would not be excluded.
• Hypersensitivity to any somatostatin analogues, to the Investigational Medicinal Products (IMPs) active substance or to any of the excipients.
• Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the Investigator, could prevent adhering to radiation safety instructions.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (65)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

RECRUITING

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

RECRUITING

Hartford Hospital

Hartford, Connecticut, 06102, United States

RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

St Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

RECRUITING

LSU Medical Center

New Orleans, Louisiana, 70112, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202-2689, United States

RECRUITING

Mount Sinai Medical Center

New York, New York, 10029-6574, United States

RECRUITING

Piedmont Healthcare

Winston-Salem, North Carolina, 27103, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

TxO Austin Midtown

Austin, Texas, 78705, United States

ACTIVE NOT RECRUITING

Texas Oncology

Dallas, Texas, 75251, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

RECRUITING

Blue Ridge Cancer Center

Wytheville, Virginia, 24382, United States

RECRUITING

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

RECRUITING

Novartis Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

Novartis Investigative Site

London, Ontario, N6A 5W9, Canada

RECRUITING

Novartis Investigative Site

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Novartis Investigative Site

Beijing, 100036, China

RECRUITING

Novartis Investigative Site

Beijing, 100730, China

RECRUITING

Novartis Investigative Site

Beijing, 102200, China

RECRUITING

Novartis Investigative Site

Shanghai, 200032, China

RECRUITING

Novartis Investigative Site

Bron, 69677, France

RECRUITING

Novartis Investigative Site

Clichy, 92110, France

RECRUITING

Novartis Investigative Site

Montpellier, 34298, France

RECRUITING

Novartis Investigative Site

Nantes, 44093, France

RECRUITING

Novartis Investigative Site

Pessac, 33604, France

RECRUITING

Novartis Investigative Site

Toulouse, 31059, France

RECRUITING

Novartis Investigative Site

Erlangen, 91054, Germany

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

München, 80377, Germany

RECRUITING

Novartis Investigative Site

Budapest, H-1083, Hungary

RECRUITING

Novartis Investigative Site

Szeged, 6725, Hungary

RECRUITING

Novartis Investigative Site

Cona, FE, 44124, Italy

RECRUITING

Novartis Investigative Site

Genova, GE, 16132, Italy

RECRUITING

Novartis Investigative Site

Milan, MI, 20133, Italy

RECRUITING

Novartis Investigative Site

Rozzano, MI, 20089, Italy

RECRUITING

Novartis Investigative Site

Pisa, PI, 56126, Italy

RECRUITING

Novartis Investigative Site

Roma, RM, 00168, Italy

RECRUITING

Novartis Investigative Site

Roma, RM, 00189, Italy

RECRUITING

Novartis Investigative Site

Milan, 20141, Italy

RECRUITING

Novartis Investigative Site

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

Novartis Investigative Site

Utrecht, 3584 CX, Netherlands

RECRUITING

Novartis Investigative Site

Gdansk, 80-214, Poland

RECRUITING

Novartis Investigative Site

Gliwice, 44 101, Poland

RECRUITING

Novartis Investigative Site

Krakow, 30-688, Poland

RECRUITING

Novartis Investigative Site

Poznan, 60-355, Poland

RECRUITING

Novartis Investigative Site

Warsaw, 02-351, Poland

RECRUITING

Novartis Investigative Site

Warsaw, 04-141, Poland

RECRUITING

Novartis Investigative Site

Seoul, 03080, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 03722, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 05505, South Korea

RECRUITING

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Novartis Investigative Site

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08035, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28034, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28040, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28041, Spain

RECRUITING

Novartis Investigative Site

Salamanca, 37007, Spain

RECRUITING

Novartis Investigative Site

London, SE5 9RS, United Kingdom

RECRUITING

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor; Lymphoma, Follicular

Interventions

pasireotide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2024
• First Posted: January 20, 2025
• Study Start: May 30, 2025
• Primary Completion (Estimated): December 8, 2028
• Study Completion (Estimated): January 23, 2034
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (4); ES (7); US (19); FR (6); IT (8); DE (3); HU (2); CA (4); PL (6); KR (3); NL (2); GB (1)