Ipilimumab and Nivolumab for the Treatment of Stage III-IV Unresectable Metastatic Melanoma

NCT04967196 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: MC200711NCI-2021-0686620-013238
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial identifies the best dose of ipilimumab that can be administered through the DoseConnect™ device followed by nivolumab in treating patients with stage III melanoma that cannot be removed by surgery (unresectable) or stage IV melanoma that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Melanoma; Unresectable Melanoma

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose (MTD) of ipilimumab administration via the DoseConnect device in combination with nivolumab

  MTD is defined as the dose level where at most 1 of the 6 patients treated at that dose level develops a dose-limited event (DLE) during the first cycle of treatment and neither a Grade 3 or worse adverse event (AE) attributable to either drug or device or a Grade 2 or worse AE lasting ≥1 week and attributable to device reported after the first cycle of treatment.

  Up to 21 days

• Incidence of adverse events

  The maximum grade of each type of adverse event will be recorded for each patient. For each adverse event reported by dose level, the percentage of patients developing any degree of that adverse event as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

  Up to 21 days

• Progression-free survival

  Defined as the time from study entry to the documentation of disease progression.

  Up to 2 years

• Overall survival

  Defined as the time from study entry to death.

  Up to 2 years

Other Outcomes (1)

• Immune parameter analysis

  Up to 2 cycles (1 cycle = 21 days)

Study Arms (2)

Cohort A (ipilimumab DC and IV, nivolumab) CLOSED

EXPERIMENTAL

Patients receive ipilimumab intra-lymphatically via DoseConnect™ on day 1 of cycle 1 and IV over 30 minutes on day 1 of cycles 2-4. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo lymphatic imaging with ICG prior to treatment start and blood sample collection throughout the study. (CLOSED TO ENROLLMENT)

Biological: Ipilimumab; Biological: Nivolumab; Procedure: Lymph Node Assessment; Procedure: Biospecimen Collection

Cohort B (Ipilimumab DC and nivolumab IV)

EXPERIMENTAL

Patients receive ipilimumab intra-lymphatically via DoseConnect™ and nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study and may optionally undergo lymphatic imaging with ICG prior to treatment start.

Biological: Ipilimumab; Biological: Nivolumab; Procedure: Lymph Node Assessment; Procedure: Biospecimen Collection

Interventions

Ipilimumab BIOLOGICAL

Given via DoseConnect device or IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Cohort A (ipilimumab DC and IV, nivolumab) CLOSED; Cohort B (Ipilimumab DC and nivolumab IV)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Cohort A (ipilimumab DC and IV, nivolumab) CLOSED; Cohort B (Ipilimumab DC and nivolumab IV)

Lymph Node Assessment PROCEDURE

Undergo lymphatic imaging with ICG

Also known as: Lymph Node Examination

Cohort A (ipilimumab DC and IV, nivolumab) CLOSED; Cohort B (Ipilimumab DC and nivolumab IV)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort A (ipilimumab DC and IV, nivolumab) CLOSED; Cohort B (Ipilimumab DC and nivolumab IV)

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
• Measurable disease as defined below:
• A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as \>= 2.0 cm with chest x-ray, or as \>= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI)
• A superficial non-nodal lesion is measurable if its longest diameter is \>= 1.0 cm in diameter as assessed using calipers (e.g., skin nodules) or imaging. In the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended.
• A malignant lymph node is considered measurable if its short axis is \> 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).
• NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease.
• Histologically or cytologically confirmed diagnosis of unresectable stage III or IV metastatic melanoma, meeting one of the following criteria:
• Progressed after at least one line of FDA approved therapy \[either immune checkpoint inhibitor (ICI) or targeted therapy\]
• Recurrent disease following initial surgical resection (may or may not have received adjuvant therapy)
• Newly diagnosed or recurrent in-transit metastatic melanoma (may or may not be treatment naïve)
• Progressed on at least one line of therapy containing anti-PD-1, antiPD-L1, or a BRAF inhibitor
• Hemoglobin \>= 8.0 g/dL (obtained =\< 15 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 15 days prior to registration)
• Platelet count \>= 75,000/mm\^3 (obtained =\< 15 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 15 days prior to registration)

You may not qualify if:

• Metastatic sites that drain lymphatic fluid into nodal beds which are not amenable to lymphatic infusion
• Sites of metastases limited only to the head and neck
• Sites of metastatic disease limited to the lungs and/or hilar lymph nodes
• Metastatic uveal melanoma
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential who are unwilling to employ adequate contraception
• Persons expecting to conceive or father children during the study or within 180 days (6 months) after the last treatment on this study
• Active central nervous system (CNS) metastases not previously treated
• NOTE: patients with history of previously treated CNS metastases, not demonstrating evidence of progression for at least 12 weeks will be allowed
• NOTE: patients with leptomeningeal metastases are not eligible
• Any of the following prior therapies:
• Allogeneic hematopoietic stem cell transplantation (HSCT)
• Solid organ transplantation

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab; Specimen Handling

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; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Anastasios Dimou, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: July 19, 2021
• Study Start: September 16, 2021
• Primary Completion: April 17, 2024
• Study Completion: April 17, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-12

Locations

US (1)