Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma

Trial Title: Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma

NCT ID: NCT06365619

Condition: Melanoma

Conditions: Official terms:
Melanoma
Nivolumab
Ipilimumab

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Ipilimumab
Description: Two cycles of neoadjuvant ipilimumab prior to surgical resection.
Arm group label: Treatment: All Patients

Intervention type: Drug
Intervention name: Nivolumab
Description: two cycles of neoadjuvant nivolumab prior to surgical resection.
Arm group label: Treatment: All Patients

Summary: The goal of this clinical trial is to study the impact of Neoadjuvant ipilimumab and nivolumab for melanoma patients that had recurrence during or after adjuvant anti-PD-1 therapy. Participants will receive 2 cycles of treatment prior to their standard of care surgery. After surgery participants will receive standard of care adjuvant therapy and be followed for response.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Subjects aged ≥ 18 years. - Histologically confirmed Stage IIIB-D or Stage IV recurrent metastatic melanoma that is resectable or borderline resectable as determined by a Surgical Oncologist. - Recurrent disease at eligibility must have been confirmed with biopsy while receiving or within 3 months of completion of adjuvant anti-PD1 therapy. - ECOG Performance Status ≤ 1. - Adequate organ function as defined as: - Hematologic: - Absolute neutrophil count (ANC) ≥ 1500/mm3 - Platelet count ≥ 100,000/mm3 - Hemoglobin ≥ 10 g/dL - Hepatic: - Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) - AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN ----Subjects with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN. - Renal: - Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula: - For subjects of childbearing potential: Negative pregnancy test or evidence of post-menopausal status or evidence of permanent surgical sterilization. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Subjects < 50 years of age: - Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and - Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution - Subjects ≥ 50 years of age: - Amenorrheic for ≥ 12 months following cessation of all exogenous hormonal treatments; or - Had radiation-induced menopause with last menses >1 year ago; or - Had chemotherapy-induced menopause with last menses >1 year ago - Subjects of childbearing potential and subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.3.1. - Subject has adequate archival tissue or agrees to undergo a fresh tissue biopsy if sufficient archival tissue is unavailable. - Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator. - Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: - Receiving other investigational agents currently or within 28 days of study treatment. - Prior systemic anti-cancer therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter. - Prior radiotherapy 45 days prior to the first dose of study treatment. - Major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery. - Active infection requiring the use of systemic antibiotics. - Systemic steroid therapy greater than physiologic equivalent (10mg prednisone/day) or any other form of systemic immunosuppressive therapy within 7 days prior to registration. - Active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety - Known brain metastases or cranial epidural disease. - Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions: --Cardiovascular disorders: - Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias. - Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose. - QTc prolongation defined as a QTcF > 500 ms. - Known congenital long QT. - Left ventricular ejection fraction < 55%. - Uncontrolled hypertension defined as ≥ 140/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes. - Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, [subjects may not receive the drug through a feeding tube], social/psychological issues, etc.) - HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. --Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial. - Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (positive HBV surface antigen (HBsAg) result), or hepatitis C. --Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. - Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study. - Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3). - Subjects taking prohibited medications as described in Section 6.7.2. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Huntsman Cancer Institute

Address:
City: Salt Lake City
Zip: 84112
Country: United States

Status: Recruiting

Contact:
Last name: Kaitlin Stephens

Phone: 801-213-8494
Email: Kaitlin.Stephens@hci.utah.edu

Start date: November 2024

Completion date: August 2029

Lead sponsor:
Agency: University of Utah
Agency class: Other

Source: University of Utah

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06365619