A Clinical Trial: Adjuvant Low-dose Ipilimumab + Nivolumab After Resection of Melanoma Macrometastases

NCT02941744 | Completed Phase 1

• 1 other identifier: 2016-BN-001
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Nivolumab (OpdivoTM, BMS), a human IgG-4 anti-PD-1 monoclonal antibody has demonstrated anti-tumor activity in patients with advanced melanoma. The investigators postulate that patients with melanoma nivolumab have a comparable tumor response rate at a dose range of 0.1 to 10 mg/kg q2wks. Ipilimumab (YervoyTM, BMS), a human IgG-1 anti-CTLA-4 monoclonal antibody improves the survival of patients with advanced melanoma. Adjuvant therapy with ipilimumab improves the relapse-free survival after complete resection of high-risk stage III melanoma (EORTC 18071). Combined treatment with ipilimumab plus nivolumab improves the tumor response rate and overall survival of patients with advanced melanoma but is associated with a higher incidence of immune related adverse events (CheckMate 067).Nivolumab and ipilimumab have distinct immunological mechanisms that can be revealed by analyzing TCR usage in blood lymphocytes.

Conditions

Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

Keywords

nivolumab; ipilimumab; low fixed dose; adjuvant therapy; Melanoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  to evaluate the safety of the investigational regimen of adjuvant low-dose ipilimumab plus nivolumab

  2year

Secondary Outcomes (1)

• to measure t cell repertoire before and after treatment with low dose ipilimumab and nivolumab with immunoseq.

  2years

Study Arms (1)

IpNiv

EXPERIMENTAL

low fixed dose ipilimumab plus low fixed dose nivolumab

Drug: nivolumab; Drug: ipilimumab

Interventions

nivolumab DRUG

low fixed dose ipilimumab in combination with nivolumab

Also known as: Opdivo

IpNiv

ipilimumab DRUG

low fixed dose ipilimumab in combination with nivolumab

Also known as: Yervoy

IpNiv

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must be either Stage IIIb/c or Stage IV AJCC (7th edition) and have histologically confirmed melanoma that is completely surgically resected in order to be eligible. Subjects must have been surgically rendered free of disease with negative margins on resected specimens. Please refer to Appendix 1 or description of AJCC 7th editions of TNM and staging.
• If Stage III melanoma (whether Stage IIIb or IIIc) the subjects must have clinically detectable lymph nodes that are confirmed as malignant on the pathology report Clinically detectable lymph nodes are defined as:
• A palpable node (confirmed as malignant by pathology)
• A non-palpable but enlarged lymph node by CT (at least 15 mm in short axis) and confirmed as malignant by pathology
• A PET positive lymph node of any size confirmed by pathology
• Evidence of pathologically macrometastatic disease in one or more lymph nodes defined by one or more foci of melanoma at least 1cm in diameter
• All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed
• Complete resection of Stage III disease that is documented on the surgical and pathology reports or complete resection of Stage IV disease with margins negative that is documented on the pathology report.
• Complete resection must be performed within 16 weeks prior to recruitment
• Subjects must not have received systemic medical anti-cancer treatment (postsurgical local/locoregional radiation therapy applied according to local standard practice is allowed)
• All subjects must have disease-free status documented by a complete physical examination and total body PET/CT imaging within 4 weeks prior to recruitment.
• ECOG performance status score of 0 or 1 (Appendix 2)
• In order to be recruited, tumor tissue from the resected site of disease must be provided for biomarker analyses. If insufficient tumor tissue content is provided for analysis, acquisition of additional archived tumor tissue (block and /or slides) for the biomarker analysis is required.
• Prior treated central nervous system (CNS) metastases must be without MRI evidence of recurrence for at least 4 weeks after treatment, subjects must be off immunosuppressive doses of systemic steroids (\> 10 mg/day or equivalent) for at least 14 days prior to study drug administration, and must have returned to neurologic baseline post-operatively. The 4-week period of stability is measured after the completion of the neurologic interventions, ie surgery and/or radiation
• In addition to neurosurgery to treat CNS metastases, adjuvant radiation after the resection of CNS metastasis is allowed. Immunosuppressive doses of systemic steroids (doses \< 10 mg/day prednisone or equivalent) must be discontinued at least 14 days before study drug administration

You may not qualify if:

• Subjects with leptomeningeal metastases
• History of ocular/uveal melanoma
• Medical History and Concurrent Diseases
• Subjects with previous non-melanoma malignancies are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period (exceptions include but are not limited to, non-melanoma skin cancers; in situ bladder cancer, in situ gastric cancer, or in situ colon cancers; in situ cervical cancers/dysplasia; or breast carcinoma in situ)
• Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that a BMS medical monitor be consulted prior to signing informed consent.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• Prior therapy for melanoma except surgery for the melanoma lesion(s) and except adjuvant RT after neurosurgical resection for CNS lesions. Specifically subjects who received prior therapy with interferon, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or checkpoint pathways) are not eligible.
• Treatment directed against the resected melanoma (eg, chemotherapy, targeted agents, biotherapy, or limb perfusion) that is administered after the complete resection.
• Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive protocol therapy.
• Physical and Laboratory Test Findings
• Positive test for hepatitis B virus surface antigen (HBVsAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Allergies and Adverse Drug Reaction
• History of Grade ≥3 allergy to humanized monoclonal antibodies
• Prisoners or subjects who are involuntarily incarcerated

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead

Study Sites (1)

UZ Brussel

Jette, Brabant, 1090, Belgium

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bart Neyns, MD Phd

  physician

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2016
• First Posted: October 21, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2019
• Last Updated: January 24, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)