Cabozantinib in Combination With Avelumab in Patients Refractory to Standard Chemotherapy With Advanced Neuroendocrine Neoplasias G3 (NEN G3)

NCT05289856 | Active Not Recruiting Phase 2

• 2 other identifiers: CaboAveNEC2021-000986-34
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of the CaboAveNEC trial is to investigate the clinical activity and safety of Cabozantinib in combination with avelumab in patients refractory to standard chemotherapy with advanced neuroendocrine neoplasias G3 (NEN G3).

Conditions

Cancer

Keywords

neuroendocrine neoplasias (NEN); NET G3; NEC G3; avelumab; cabozantinib

Outcome Measures

Primary Outcomes (1)

• Disease control rate (DCR: CR, PR, SD)

  Disease control rate (DCR: CR, PR, SD) according to iRECIST after 16 weeks from start of treatment until documented disease progression (PD)

  16 weeks

Secondary Outcomes (12)

• Disease control rate (DCR: CR, PR, SD)

  week 8, week 24, week 48

• Objective response rate (ORR)

  week 8, week 16, week 24, week 48

• Best overall response (BOR)

  week 8, week 16, week 24, week 48

• Duration of disease control (DDC)

  week 48

• Time to response (TTR)

  week 48

Other Outcomes (3)

• Correlation of the primary and secondary endpoints with the differentiation of the NEN G3

  week 8, week 16, week 24, week 48

• Comparison of the efficacy and tolerability of the combination treatment with Cabozantinib and Avelumab to the monotherapy with Avelumab

  week 8, week 16, week 24, week 48

• Evaluation of tumor growth rate (TGR)

  week 8, week 16, week 24, week 48

Study Arms (1)

combination of Avelumab and Cabozantinib

EXPERIMENTAL

800 mg Avelumab every 2 weeks and 40 mg Cabozantinib daily

Drug: combination of Avelumab and Cabozantinib

Interventions

combination of Avelumab and Cabozantinib DRUG

Cabozantinib 40 mg daily PO in combination with Avelumab at a dose of 800 mg as a 1h intravenous (i.v.) infusion every two weeks (q2w) until disease progression (PD), unacceptable toxicity, or any criterion for treatment withdrawalis met, for a maximum of 12 months

Also known as: Bavencio, Cabometyx

combination of Avelumab and Cabozantinib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histologically proven neuroendocrine neoplasia NEN G3 (WHO 2010/2019)
• One block or 20 slides (cut at 4 microns) of archival tumor tissue to perform central pathological review and biomarker assessment and for translational research
• No curative option available
• Progression within 9 months before study initiation and after at least one chemotherapy (platinum based chemotherapy or STZ/TEM/DTIC based chemotherapy)
• Presence of measurable disease as per RECIST1.1 criteria
• Adequate organ and bone barrow functionn:
• Hematologic: absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)
• Hepatic: total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 × ULN for subjects with documented metastatic disease to the liver)
• Renal: estimated creatinine clearance ≥ 60 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• Pregnancy and contraception:
• Pregnancy test: Negative serum or urine pregnancy test at screening for women of childbearing potential.
• Contraception: Women of child-bearing potential (WOCBP) and men who are able to father a child, willing to be abstinent or use highly effective methods of birth control that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at informed consent, for the duration of study participation and for at least 30 days for female and 90 days for male patients after last dose of avelumab and at least for 4 months after last dose of cabozantinib
• ECOG Performance Status 0 - 1
• Life expectancy of at least 12 weeks according to the assessment of the investigator

You may not qualify if:

• Merkel Cell carcinoma (MCC) or small cell lung cancer (SCLC)
• Typical or Atypical Carcinoid of the lung with a Ki67 \< 20%
• Prior therapy with any TKI or immune therapy
• Neuroendocrine neoplasias that are potentially curable by surgery
• Major surgery within 4 weeks before first dose of study medication. Complete wound healing must be observed at least 10 days prior to enrollment.
• Patients who are at increased risk for severe haemorrhage
• TACE, TAE, SIRT or PRRT within 8 weeks before first dose of study medication
• Patients pretreated with Interferon as last treatment line prior to study entry
• Concurrent anticancer treatment after start of trial treatment (e.g., cyto¬reductive therapy, TKI therapy, mTOR inhibitor therapy, radiotherapy \[with the exception of palliative radiotherapy\], immune therapy, or cytokine therapy except for erythropoietin or use of any investigational drug).
• Concurrent treatment with strong inducers of cytochrome P450 3A4 (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's wort) and strong inhibitors of cytochrome P450 3A4 (eg, ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, and ritonavir), warfarin (due to its high protein bound)
• Immunosuppressants: Current use of immunosuppressive medication, EXCEPT for the following:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Prior organ transplantation, including allogeneic stem cell transplantation

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead
• Ipsen: collaborator
• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (2)

Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

I. Medizinische Klinik und Poliklinik, Endokrinologie und Stoffwechselerkrankungen, Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

MeSH Terms

Conditions

Neoplasms

Interventions

cabozantinib; avelumab

Study Officials

• Matthias M Weber, MD

  Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. Medizinische Klinik und Poliklinik, Abteilung Endokrinologie und Stoffwechselkrankheiten, D-55131 Mainz, Germany

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 22, 2022
• Study Start: March 28, 2022
• Primary Completion: March 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)