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Neuroendocrine CarcinomaPhase 1/2NET-001NCT03278405

Avelumab in G3 NEC

A Phase 1/2 study testing Avelumab in people with Neuroendocrine Carcinoma, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a single-center, single-arm, open-label, pilot trial to evaluate the efficacy and safety of avelumab in subjects with unresectable or metastatic, Grade 3, poorly-differentiated neuroendocrine.carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neuroendocrine Carcinoma
What is being tested?
Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteCanada
Study dates
15 Nov 2017to 12 Mar 2020
Phase
Phase 1/2
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

  • Adults (males or females), aged 18 years or older with pathologically confirmed, advanced (unresectable or metastatic) neuroendocrine tumour from a gastroenteropancreatic or lung source. Both participants with functional NETs and those with nonfunctional NETs shall be eligible for this study.
  • Histologically confirmed, WHO Grade 3, poorly-differentiated NEC.
  • Has received 0,1 or 2 prior lines of systemic therapy (chemotherapy, PRRT, targeted therapies such as everolimus or sunitinib). Somatostatin analogues are not considered a line of therapy for the purposes of this criterion.
  • Radiological documentation of disease progression within 24 weeks of study enrolment. Disease progression must be demonstrated on two scans less than one year apart.
  • Participants previously treated with any systemic therapies are eligible to enroll if disease progression is documented during or after their last treatment.
  • Measurable disease as assessed by CT scan of the chest, abdomen and pelvis which is suitable for accurate repeated measurements (according to RECIST v1.1).
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  • ECOG performance status 0-2.
  • Adequate bone marrow function (ANC > 1.5 x 109/L; Platelets >100 x109/L; haemoglobin > 90 g /L).
  • Adequate liver function defined by a total bilirubin level ≤1.5xULN and AST and ALT levels ≤2.5xULN for participants (or AST and ALT levels ≤ 5xULN for participants with documented metastatic disease to the liver).
  • Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
  • Willing and able to comply with all study requirements, including timing and/or nature of treatment and required assessments.
  • Signed, written informed consent.
  • Evidence of post-menopausal status, or negative urine or serum pregnancy test for female pre-menopausal participants (within approximately 14 days prior to enrolment). Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical explanation.
  • Highly effective contraception for both male and female participants if the risk of conception exists (note: The effects of the IP on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraceptions, defined as methods with a failure rate of less than 1% per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after avelumab treatment.)

Who cannot join

  • Grade 1-2 NET, or Grade 3 well-differentiated neuroendocrine tumour, or mixed adenoneuroendocrine carcinomas (MANEC)
  • NETs confirmed to be from a primary other than the gastrointestinal tract, pancreas or lung.
  • Prior use of PD-1, PD-L1 or CTLA-4 inhibitors
  • Life expectancy of ≤3 months
  • Concurrent treatment with other anticancer therapy (except somatostatin analogues for the purposes of functional control). Participants on somatostatin analogues for anti-proliferative therapy should have this therapy ceased, and would be eligible for enrolment if they have not received somatostatin analogues in the past 14 days.
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, with exception to:
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  • Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
  • Active infection requiring systemic therapy.
  • History of primary autoimmunodeficiency
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Prior organ transplantation, including allogeneic stem cell transplantation
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  • Major surgery in the 2 weeks prior to randomization. Surgery with intent to debulk metastatic disease is allowed, as long as there is sufficient residual disease for RECIST measurements (see inclusion criteria 5).
  • Participants with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for three years.
  • All participants with brain metastases and any of the following:
  • They have not received local treatment to known brain metastases
  • They have been clinically unstable in the 2 weeks prior to enrolment
  • Requirement for treatment with systemic steroids exceeding the equivalent of 10mg oral prednisone per day
  • Ongoing neurological symptoms related to brain metastases
  • Leptomeningeal metastases
  • Pregnancy, lactation, or inadequate contraception.
  • Significant acute or chronic infections including, among others:
  • Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
  • Active tuberculosis
  • Testing for these diseases is not mandatory unless clinically indicated.
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
  • Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Known alcohol or drug abuse
  • Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Vaccination within 4 weeks of the first dose of avelumab and while on trial, except for administration of inactivated vaccines
  • Inability to obtain sufficient tumour tissue (whether archival or fresh) for PD-L1 testing. A core biopsy, endoscopic biopsy or surgical resection specimen shall be considered adequate tissue; a fine needle aspirate/biopsy will be considered insufficient tissue.
  • Prior treatment for study indication with:
  • Peptide Receptor Radiouclide Therapy (PRRT) administered within 3 months of enrolment
  • Hepatic intra-arterial embolization, radio-frequency ablation, or cryoablation within 4 weeks of enrolment

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N3M5

Other trials in Canada

About this study

Official title: A Pilot Study of Avelumab in Unresectable/Metastatic, Progressive, Poorly Differentiated Grade 3 Neuroendocrine Carcinomas

This is a single-center, single-arm, open-label, pilot trial to evaluate the efficacy and safety of avelumab in subjects with unresectable or metastatic, Grade 3, poorly-differentiated neuroendocrine.carcinoma.

Being tested
Avelumab
Medical subject headings
Carcinoma, Neuroendocrine

What participants receive

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

  • AvelumabDrug

    Avelumab will be administered intravenously as an infusion, at a dose of 10 milligram per kilogram once every 2 weeks, until occurence of progressive disease, unacceptable toxicity, or any of the other criteria for withdrawal listed in the protocol .

Study groups in NCT03278405
Study groupRoleWhat they receive
Intervention ArmExperimentalTreatment with avelumab
Receives: Drug: Avelumab

What is being measured

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

  1. Overall response rate (ORR)

    The overall response rate will be defined as the number of participants with confirmed complete response or partial response (CR or PR) recorded as the best response over the study period, divided by the number of participants evaluable for response as defined by RECIST version 1.1.

    Measured: Up to 2 years

Secondary outcomes (13)

  1. Disease control rate (DCR)

    The DCR will be defined as the number of patients with confirmed CR, PR or stable disease (SD) recorded as the best response over the study period, divided by the number of participants evaluable for response as defined by RECIST version 1.1.

    Measured: Up to 2 years

  2. Duration of response

    Time from documentation of tumour response to disease progression

    Measured: Up to 2 years

  3. Progression-free survival (PFS)

    PFS is defined as the time from first administration of study drug to the date of documented confirmed progression or death, whichever comes first

    Measured: Up to 2 years

  4. Overall survival (OS)

    OS is defined as the time from first administration of drug to date of death.

    Measured: Up to 2 years

  5. Rates of treatment-emergent adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03

    Measured: Up to 90 days after the last dose is administered

  6. ORR by irRECIST version 1.1

    Measured: Up to 2 years

  7. DCR by irRECIST version 1.1

    Measured: Up to 2 years

  8. Duration of response by irRECIST version 1.1

    Measured: Up to 2 years

  9. PFS by irRECIST version 1.1

    Measured: Up to 2 years

  10. OS at 1 year

    Measured: 1 year

  11. OS at 2 years

    Measured: 2 years

  12. PFS at 1 year

    Measured: 1 year

  13. PFS at 2 years

    Measured: 2 years

Timeline

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

  1. First posted11 Sep 2017
  2. Study start15 Nov 2017
  3. Primary completion9 Aug 2019
  4. Study completion12 Mar 2020

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03278405
Sponsor's protocol ID
415-2016
Acronym
NET-001
Status last verified
Mar 2020
First submitted
23 Aug 2017
Last updated
18 Mar 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chan DL, Rodriguez-Freixinos V, Doherty M, Wasson K, Iscoe N, Raskin W, Hallet J, Myrehaug S, Law C, Thawer A, Nguyen K, Singh S. Avelumab in unresectable/metastatic, progressive, grade 2-3 neuroendocrine neoplasms (NENs): Combined results from NET-001 and NET-002 trials. Eur J Cancer. 2022 Jul;169:74-81. doi: 10.1016/j.ejca.2022.03.029. Epub 2022 May 2.

    PubMed 35504244

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Avelumab in people with Neuroendocrine Carcinoma, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

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 14 inclusion and 36 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: finished, as of the sponsor's last update on 18 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) (time frame: Up to 2 years). 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 NCT03278405, which also lists 1 linked publication.

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 18 Mar 2020.

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