A Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination Immunotherapy

Metastatic Melanoma Clinical Trial

Official title:

A Phase II Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination Immunotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03122522
• Other study ID #: 17-162
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 17, 2017
• Est. completion date: April 2025

Study information

• Verified date: May 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will help determine whether 2 doses of the combination (ipilimumab + nivolumab) is sufficient for patients with early benefit compared to the usual way of trying to give 4 doses. If patients do not show early benefit after 2 doses, patients will be able to continue with additional ipilimumab + nivolumab, even beyond the standard 4 doses if felt in the best interest of the patient.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic diagnosis of unresectable III or stage IV metastatic melanoma.

• Subjects must have at least 1 extracranial, unresectable, non-bony lesion that is measurable radiographically (based on RECIST 1.1).

• No prior CTLA-4 or PD-1/PD-L1 therapy for the treatment of metastatic disease.

• ECOG performance status of 0-1.

• Life expectancy = 4 months.

• Screening laboratory parameters:

• White blood cell (WBC) count = 2000/µL;

• Absolute neutrophil count (ANC) = 1500/µL;

• Platelets = 100,000/µL;

• Hemoglobin (Hgb) = 9 g/dL;

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × upper limit of normal (ULN);

• Total bilirubin = 1.5 × ULN (< 3 mg/dL for subjects with Gilbert's disease);

• Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL] Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL]

• Age = 18 years.

• Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 23 weeks after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.

[Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).] Nonsterilized males who are sexually active with a female partner of childbearing potential must use 2 acceptable methods of effective contraception from Day 1 and for 31 weeks after receipt of the final dose of investigational product.

Acceptable methods of effective contraception are described in the following table:

• Barrier Methods - Male condom plus spermicide, cap plus spermicide, or diaphragm plus spermicide.

• Intrauterine Device Methods-Copper T, or Levonorgestrel-releasing intrauterine system (e.g., Mirena®), also considered a hormonal method.

• Hormonal Methods-Implants, hormone shot or injection, combined pill, minipilimumabll, or Patch.

Exclusion Criteria:

• Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (>10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

• History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis).

• Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator.

• Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C infection. Antibody to Hepatitis B or C without evidence of active infection may be allowed.

• History of severe allergic reactions to any unknown allergens or any components of the study drugs.

• Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).

• Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.

• Lack of availability for immunological and clinical assessments or post-study follow-up contact to determine relapse and survival.

• Women who are breastfeeding or who are pregnant as evidenced by a positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) performed within 14 days of the first dose of study drug and by a urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours of the first dose of study drug(s).

• Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Drug:
• ipilimumab
ipilimumab 3mg/kg
• nivolumab
nivolumab 1mg/kg

Locations

Country	Name	City	State
United States	Lehigh Valley Health Network (Data Collection Only)	Allentown	Pennsylvania
United States	JOHNS HOPKINS HOSPITAL (Data Analysis Only)	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Brigham and Women's Hospital (Data and Specimen Analysis Only)	Boston	Massachusetts
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Healthcare Alliance (Data Collection Only)	Hartford	Connecticut
United States	Jaykumar Thumar	Hartford	Connecticut
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Columbia University (Data Analysis Only)	New York	New York
United States	Hospital for Special Surgery (Data Analysis)	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	objective response rate	RECIST 1.1.	at 6 weeks

External Links

•   Memorial Sloan Kettering Cancer Center