- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03278405
Avelumab in G3 NEC (NET-001)
March 17, 2020 updated by: Sunnybrook Health Sciences Centre
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ontario
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Toronto, Ontario, Canada, M4N3M5
- Sunnybrook Health Sciences Centre
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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).
- 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.)
Exclusion Criteria:
- 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:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Intervention Arm
Treatment with avelumab
|
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 .
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR)
Time Frame: Up to 2 years
|
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.
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease control rate (DCR)
Time Frame: Up to 2 years
|
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.
|
Up to 2 years
|
Duration of response
Time Frame: Up to 2 years
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Time from documentation of tumour response to disease progression
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Up to 2 years
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Progression-free survival (PFS)
Time Frame: Up to 2 years
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PFS is defined as the time from first administration of study drug to the date of documented confirmed progression or death, whichever comes first
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Up to 2 years
|
Overall survival (OS)
Time Frame: Up to 2 years
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OS is defined as the time from first administration of drug to date of death.
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Up to 2 years
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Rates of treatment-emergent adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03
Time Frame: Up to 90 days after the last dose is administered
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Up to 90 days after the last dose is administered
|
|
ORR by irRECIST version 1.1
Time Frame: Up to 2 years
|
Up to 2 years
|
|
DCR by irRECIST version 1.1
Time Frame: Up to 2 years
|
Up to 2 years
|
|
Duration of response by irRECIST version 1.1
Time Frame: Up to 2 years
|
Up to 2 years
|
|
PFS by irRECIST version 1.1
Time Frame: Up to 2 years
|
Up to 2 years
|
|
OS at 1 year
Time Frame: 1 year
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1 year
|
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OS at 2 years
Time Frame: 2 years
|
2 years
|
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PFS at 1 year
Time Frame: 1 year
|
1 year
|
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PFS at 2 years
Time Frame: 2 years
|
2 years
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Correlation of PD-L1 status with response to avelumab
Time Frame: Up to 2 years
|
Up to 2 years
|
Correlation of mutational load and T-cell repertoire analysis with response to avelumab
Time Frame: Up to 2 years
|
Up to 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Simron Singh, Sunnybrook Health Sciences Centre
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 15, 2017
Primary Completion (Actual)
August 9, 2019
Study Completion (Actual)
March 12, 2020
Study Registration Dates
First Submitted
August 23, 2017
First Submitted That Met QC Criteria
September 8, 2017
First Posted (Actual)
September 11, 2017
Study Record Updates
Last Update Posted (Actual)
March 18, 2020
Last Update Submitted That Met QC Criteria
March 17, 2020
Last Verified
March 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 415-2016
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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