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Neuroendocrine Tumours (NET)Phase 2NCT04525638

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

A Phase 2 study testing 177Lu-Dotatate and Nivolumab in people with Neuroendocrine Tumours (NET) and Neuroendocrine Carcinomas (NEC), run by Fundación de investigación HM at 5 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
177Lu-Dotatate and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
5 sitesSpain
Study dates
29 Jun 2020to 30 Sep 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).
  • Serum albumin ≥ 3.0 g/dL (or serum albumin < 3.0 g/dL if prothrombin time is within the normal range).
  • Female patients must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods of contraception include intrauterine device, oral contraceptive, subdermal implant and/or double barrier.
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.
  • Recovery to Grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or asthenia).

Who cannot join

  • 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).
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  • 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.
  • Prior external beam radiation therapy to more than 25% of the bone marrow.
  • Urinary incontinence.
  • Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, esophageal, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 5 years prior to study entry AND no additional therapy is required during the study period
  • Prisoners or patients who are compulsory detained.
  • Established or suspected pregnancy or when pregnancy has not been excluded
  • Kidney failure with creatinine clearance < 30 mL/min

Trial locations and contacts

5 sites in 1 country.

Antonio Cubillo, MD contact

+34 917567800

secretaria@fundacionhm.com

5 sites in 1 country

Spain5 sites, 5 recruiting

  • Hospital Unviersitario Ramón y Cajal

    Madrid, 28029

    Teresa Alonso Gordoa, MD

    Teresa Alonso Gordoa

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Rocio García Carbonero, MD, +34913908003, rgcarbonero.ensayos@gmail.com

    Rocio García Carbonero

    Recruiting

  • Hospital Universitario Puerta de Hierro Majadahonda

    Majadahonda, Madrid, 28022

    Juan Cristobal Sanchez, MD, +34911917147

    Juan Cristobal Sanchez

    Recruiting

  • Hospital Universitario Madrid Sanchinarro

    PAU de Sanchinarro, Madrid, 28050

    Rafael Álvarez, MD

    Rafael Alvarez

    Recruiting

  • Complexo Hospitalario Universitario de Santiago

    Santiago de Compostela, Galicia, 15706

    Urbano Anido, MD, +34981950535

    Urbano Anido, MD

    Recruiting

Other trials in Spain

About this study

Official title: A Phase II Single Arm Trial Evaluating the Preliminary Efficacy of the Combination of 177Lu-DOTATATE and Nivolumab in Grade 3 Well-differentiated Neuroendocrine Tumours (NET) or Poorly Differentiated Neuroendocrine Carcinomas (NEC)

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).

Read the detailed description

Patients will have unresectable advanced, recurrent or metastatic, histologically confirmed, well-differentiated Grade 3 NET or poorly-differentiated NEC of the pancreas, gastrointestinal tract lung and unknown primary site. Thirty patients will be included in this trial, of which 15 will not have received prior chemotherapy (Cohort 1) and 15 will have received at least one prior line of chemotherapy (Cohort 2). Patient 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. Nivolumab will be administered at Day 1 and Day 15 of a 28-days cycle, starting on Cycle 1 Day 1. Patients will receive the study drugs while it is considered to be in their best interest, 177Lu-DOTATATE being administered at a maximum of 4 injection cycle. Treatment discontinuation criteria include, among others, progression, unacceptable toxicity or patient study withdrawal

Being tested
177Lu-Dotatate, Nivolumab
Medical subject headings
Neuroendocrine Tumors, Carcinoma, Neuroendocrine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 177Lu-DotatateDrug

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

  • NivolumabDrug

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

Study groups in NCT04525638
Study groupRoleWhat they receive
177Lu-DOTATATE + NivolumabExperimentalPatients 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
Receives: Drug: 177Lu-Dotatate; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    ORR assessed by RECIST v.1.1

    Measured: Week 15 (+/-1) of treatment

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    1. ORR assessed by RECIST v.1.1
    2. ORR assessed by Choi and modified RECIST for immune based therapeutics (iRECIST)

    Measured: Week 31 (+/-1) of treatment

  2. Progression-free Survival (PFS)

    Measured: Week 31 (+/-1) of treatment

  3. Number and Grade of Adverse Events

    by CTCAE v.5 criteria

    Measured: Week 31 (+/-1) of treatment

  4. Overall Survival (OS)

    Measured: Week 31 (+/-1) of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Aug 2020
  2. Study start29 Jun 2020
  3. Primary completion30 Sep 2024 (estimated)
  4. Study completion30 Sep 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
open-label, single-arm
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04525638
Sponsor's protocol ID
HMH008
Status last verified
Jul 2022
First submitted
21 Aug 2020
Last updated
2 Aug 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 177Lu-Dotatate and Nivolumab in people with Neuroendocrine Tumours (NET) and Neuroendocrine Carcinomas (NEC), run by Fundación de investigación HM at 5 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 2 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Antonio Cubillo, MD (+34 917567800, secretaria@fundacionhm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Week 15 (+/-1) of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04525638.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2022.

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