Nivolumab With Ipilimumab in Subjects With Neuroendocrine Tumors

NCT03420521 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: J17156IRB00151698
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm open-label design study looking at Nivolumab plus Ipilimumab in patients with Advanced Neuroendocrine Tumors. Patients will be dosed Nivolumab 240mg IV over 60 minutes every 2 weeks (Q2W) and Ipilimumab 1mg/kg IV over 30 minutes every 6 weeks (Q6W). One cycle will include 3 doses of Nivolumab and 1 dose of Ipilimumab. The objective of this study is to evaluate the objective response rate of combination Nivolumab and Ipilimumab in advanced, well-differentiated neuroendocrine tumors. Durability of response, and progression free survival (PFS) will also be described.

Conditions

Neuroendocrine Tumors; Carcinoid Tumor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) of Neuroendocrine Tumor (NET) of the Lung, Pancreas, and Gastrointestinal (GI) Tract

  The number of subjects who have at least one scan with an Objective Response (OR) of confirmed complete response (CR) or partial response (PR), per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by CT scan: Objective Response (OR), a response of CR or PR from baseline to PD, palliative local therapy, or subsequent anticancer therapy; Complete Response (CR), the disappearance of all target lesions and any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm; Partial Response (PR), \>= 30% decrease in the sum of the longest diameters of target lesions, compared to baseline sum diameters

  up to 24 months

Secondary Outcomes (9)

• Number of Patients Experiencing Drug-related Adverse Events

  up to 27 months

• Number of Patients Experiencing Dose-limiting Toxicities

  up to 24 months

• Progression Free Survival (PFS) at 6 Months

  6 months

• Progression Free Survival (PFS) at 12 Months

  12 months

• Progression Free Survival (PFS) at 24 Months

  24 months

Study Arms (1)

Nivolumab plus Ipilimumab

OTHER

Nivolumab 240 mg IV over 60 minutes every 2 weeks (Q2W) Ipilimumab 1mg/kg IV over 30 minutes every 6 weeks (Q6W)

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

240mg IV over 60 minutes Q2W

Also known as: Bristol Myers Squibb (BMS), BMS-936558

Nivolumab plus Ipilimumab

Ipilimumab DRUG

1mg/kg IV over 30 minutes Q6W

Also known as: Bristol Myers Squibb (BMS), BMS-734016

Nivolumab plus Ipilimumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with histologically confirmed advanced, progressive, well-differentiated nonfunctional NET of the pancreas, lung or gastrointestinal (GI) tract per the 8th International Association for the Study of Lung Cancer classification (IASLC) or the American Joint Committee on Cancer (AJCC) Staging Handbook, 7th edition. Progression must be documented over the prior 12 months.
• Measurable disease by CT or MRI per RECIST 1.1 criteria (Appendix 3); radiographic tumor assessment performed within 28 days before treatment. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site after the completion of radiation therapy.
• Prior therapy, including everolimus, octreotide, surgery, chemoradiation, is all permitted after being properly noted. This prior therapy must have been completed at least 28 days prior to study enrollment.
• Patients with lung NETs must have progressed after at least 1 line of therapy. Patients with GI NETs must have had at least 2 lines of prior therapy.
• Subjects are to have tumor tissue sample available at central lab for programmed cell death ligand 1 (PD-L1) immunohistochemistry (IHC) testing during the screening period. Subjects can initiate therapy before the result of IHC testing.
• (Stage 2 only) Subjects must be willing to undergo 2 sets of core needle biopsies (pre-treatment and at 6-8 weeks on therapy) if there are lesions amenable to biopsy. Subjects without a lesion amendable to biopsy will still be permitted to enroll provided they have an archival tumor sample for PD-L1 IHC testing. An optional core biopsy will be requested at progression.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (see Appendix 1)
• Prior palliative radiotherapy to non-central nervous system (CNS) lesions must have been completed at least 2 weeks prior to treatment. Subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of first treatment are strongly encouraged to receive palliative radiotherapy prior to treatment.
• Patients must have normal organ and marrow function as defined below:
• \- white blood cell (WBC) ≥1,500/microliters (mcL)
• \- absolute neutrophil count ≥1,000/mcL
• \- hemoglobin ≥ 8.0 g/dL
• \- platelets ≥75,000/mcL
• \- total bilirubin ≤ 1.5 x institutional ULN (patients with Gilbert's syndrome may have serum bilirubin ≤ 3 x ULN)
• \- aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN (≤ 5 x ULN in the presence of liver metastases)

You may not qualify if:

• Subjects with poorly differentiated or small cell carcinoma histology
• Subjects with disease that is amenable to surgical resection.
• Subjects with history of or active symptoms of carcinoid or hormonal syndromes are permitted if symptoms are controlled with a somatostatin analog.
• Hepatic intra-arterial embolization or peptide receptor radionuclide therapy (PRRT) within 4-8 weeks; cryoablation, radiofrequency ablation or trans-arterial chemoembolization of hepatic metastases within ≤ 4 weeks of study enrollment
• Subjects with symptomatic untreated CNS metastases are excluded.
• Subjects are eligible if CNS metastases are asymptomatic or adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment.
• In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of \<10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first treatment.
• Subjects with carcinomatous meningitis
• Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before first treatment.
• Pregnant or breast-feeding women
• Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug.
• Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Other active malignancy requiring concurrent intervention.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal replacement steroid 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Johns Hopkins Medical Institution

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Carcinoid Tumor

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Christine Hann
• Organization: Johns Hopkins University

chann1@jh.edu

410-502-0678

Study Officials

• Christine Hann, MD/PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: November 30, 2017
• First Posted: February 5, 2018
• Study Start: March 9, 2018
• Primary Completion: November 24, 2021
• Study Completion: November 24, 2021
• Last Updated: January 9, 2024
• Results First Posted: January 9, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)