A Clinical Study to Assess the Combination of Two Drugs (177Lu-DOTATATE and Nivolumab) in Neuroendocrine Tumours

NCT04525638 | Unknown Phase 2

• 1 other identifier: HMH008
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

This is a prospective, multi-centre, open-label, single-arm, stratified, exploratory, Phase 2 study evaluating the efficacy and safety of 177Lu-DOTATATE in combination with nivolumab in adult patients with Grade 3 neuroendocrine tumours (NET) or neuroendocrine carcinomas (NEC).

Conditions

Neuroendocrine Tumours (NET); Neuroendocrine Carcinomas (NEC)

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR assessed by RECIST v.1.1

  Week 15 (+/-1) of treatment

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  Week 31 (+/-1) of treatment

• Progression-free Survival (PFS)

  Week 31 (+/-1) of treatment

• Number and Grade of Adverse Events

  Week 31 (+/-1) of treatment

• Overall Survival (OS)

  Week 31 (+/-1) of treatment

Study Arms (1)

177Lu-DOTATATE + Nivolumab

EXPERIMENTAL

Patients will receive 240 mg flat dose of nivolumab intravenously as a 30-minutes infusion and 7.4 GBq 177Lu-DOTATATE intravenously as a 4-hours infusion

Drug: 177Lu-Dotatate; Drug: Nivolumab

Interventions

177Lu-Dotatate DRUG

7.4 GBq 177Lu-DOTATATE intravenously as a 4-hours infusion

177Lu-DOTATATE + Nivolumab

Nivolumab DRUG

240 mg flat dose of nivolumab intravenously as a 30-minutes infusion

177Lu-DOTATATE + Nivolumab

Eligibility Criteria

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

You may qualify if:

• Patients having voluntarily signed and dated IRB/IEC-approved written informed consent form in accordance with regulatory and institutional guidelines before the performance of any protocol-related procedures.
• Patients with advanced/metastatic, histologically confirmed, well-differentiated Grade 3 NET or poorly-differentiated NEC of the pancreas, gastrointestinal tract, lung and unknown primary site at diagnosis or after progression to one systemic treatment. Patients will be enrolled in two cohorts based on the therapy of their aforementioned cancer: Cohort 1: Patients with no previous chemotherapy. Cohort 2: Patients who have received one line of chemotherapy.
• Age ≥18 years.
• Patients must have measurable disease based on RECIST v.1.1 meeting the following criteria:
• Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation or liver embolization must show evidence of progressive disease based on RECIST v.1.1 to be deemed a target lesion.
• Patients in cohort 2 must show evidence of disease progression by radiologic image techniques according to RECIST v.1.1 within 3 months prior to signing informed consent.
• Confirmed presence of somatostatin receptors on tumour lesions based on positive PET-Gallium (SomaKit) imaging within 8 weeks prior to enrolment in the study. At least one lesion should have an uptake of 64-Gallium higher than the normal liver according to investigator judgement.
• Karnofsky Performance Score ≥ 60 and Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
• Life expectancy of ≥ 6 months.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin concentration ≥ 8.0 g/dL (5.0 mmol/L).
• WBC ≥ 2x10 9/L (2000/mm3).
• Platelets ≥75x10 9/L (75x103/mm3).
• Adequate renal function defined as serum creatinine ≤150 μmol/L or 1.7 mg/dL, or a creatinine clearance or measured glomerular filtration rate (using plasma clearance methods) of ≥ 50 mL/min.
• Adequate hepatic function defined as total bilirubin ≤3 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present).

You may not qualify if:

• Treatment with \>30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to enrolment in the study.
• Peptide receptor radionuclide therapy (PRRT) at any time prior to enrolment in the study.
• Targeted surgery, radiotherapy (external beam), chemotherapy, embolization, interferons, mTOR-inhibitors or other investigational therapy within 12 weeks prior to enrolment in the study. In Cohort 2, chemotherapy should be administered at least 4 weeks prior to first dose of the treatment.
• Prior treatment with anti-PDL-1/anti-PD-1 or anti-CTL-4 therapy.
• Known 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 with contrast to document stable disease prior to enrolment in the study.
• Uncontrolled congestive heart failure (NYHA II-IV).
• Uncontrolled diabetes mellitus as defined by a fasting blood glucose \>2 ULN.
• Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTATATE , or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTATATE, unless the tumour uptake observed by Somakit imaging during continued Octreotide treatment is at least as high as normal liver uptake observed by planar imaging.
• Acute or chronic hepatitis B (e.g., Hepatitis B surface antigen reactive), hepatitis C (e.g., HCV RNA \[qualitative\] is detected) or known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Active, known, or suspected autoimmune disease within the past 2 years. NOTE: Patients with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) and Grave's disease not requiring systemic treatment within the past 2 years are not excluded.
• Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. NOTE: Inhaled or topical steroids, and systemic steroid doses \> 10 mg daily prednisone equivalent for adrenal replacement are permitted in the absence of active autoimmune disease.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of allogeneic organ transplant.
• Known hypersensitivity to nivolumab, 177Lu-DOTATATE or its excipients.
• Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study. Patients must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before starting treatment.

Sponsors & Collaborators

• Fundación de investigación HM: lead
• Syntax for Science, S.L: collaborator

Study Sites (5)

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, Galicia, 15706, Spain

RECRUITING

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28022, Spain

RECRUITING

Hospital Universitario Madrid Sanchinarro

PAU de Sanchinarro, Madrid, 28050, Spain

RECRUITING

Hospital Unviersitario Ramón y Cajal

Madrid, 28029, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoma, Neuroendocrine

Interventions

lutetium Lu 177 dotatate; Nivolumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Antonio Cubillo, MD

  Director

  STUDY DIRECTOR

Central Study Contacts

Antonio Cubillo, MD

CONTACT

+34 917567800; secretaria@fundacionhm.com

Study Design

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

Model Details: open-label, single-arm

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: August 25, 2020
• Study Start: June 29, 2020
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)