Avelumab in G2-3 NET

NCT03278379 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 414-2016
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, open-label, phase II trial to evaluate the efficacy and safety of avelumab in subjects with unresectable or metastatic, Grade 2-3, well-differentiated neuroendocrine.tumour.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (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.

  Up to 2 years

Secondary Outcomes (13)

• Disease control rate (DCR)

  Up to 2 years

• Duration of response

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

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

  Up to 90 days after the last dose is administered

Other Outcomes (2)

• Correlation of PD-L1 status with response to avelumab

  Up to 2 years

• Correlation of mutational load and T-cell repertoire analysis with response to avelumab

  Up to 2 years

Study Arms (1)

Intervention Arm

EXPERIMENTAL

Treatment with Avelumab

Drug: Avelumab

Interventions

Avelumab DRUG

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 .

Intervention Arm

Eligibility Criteria

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

You may qualify if:

• 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 2-3, well-differentiated NETs of gastroenteropancreatic or lung origin.
• 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 g9/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.)

You may not qualify if:

• Grade 1 NET or Grade 3 poorly-differentiated neuroendocrine carcinoma, or mixed adenoneuroendocrine carcinomas (MANEC)
• NETs confirmed to be from primaries 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.
• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N3M5, Canada

Location

Related Publications (1)

• 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.

  PMID: 35504244 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

avelumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Simron Singh

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 23, 2017
• First Posted: September 11, 2017
• Study Start: November 15, 2017
• Primary Completion: July 26, 2021
• Study Completion: July 6, 2023
• Last Updated: December 24, 2024

Record last verified: 2024-11

Locations

CA (1)