Clinical trial NCT03122522: A Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination Immunotherapy
Official title: A Phase II Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination Immunotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Melanoma
Keywords: unresectable
III or stage IV
Ipilimumab
Nivolumab
17-162
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2017-04-20
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: objective response rate
timeFrame: at 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Healthcare Alliance (Data Collection Only)
state: Connecticut
city: Hartford
country: United States
facility: Jaykumar Thumar
state: Connecticut
city: Baltimore
country: United States
facility: JOHNS HOPKINS HOSPITAL (Data Analysis Only)
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital (Data and Specimen Analysis Only)
state: Massachusetts
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery (Data Analysis)
state: New York
city: New York
country: United States
facility: Columbia University (Data Analysis Only)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Allentown
country: United States
facility: Lehigh Valley Health Network (Data Collection Only)
state: Pennsylvania
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Michael Postow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Postow MA, Goldman DA, Shoushtari AN, Betof Warner A, Callahan MK, Momtaz P, Smithy JW, Naito E, Cugliari MK, Raber V, Eton O, Nair SG, Panageas KS, Wolchok JD, Chapman PB. Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study). J Clin Oncol. 2022 Apr 1;40(10):1059-1067. doi: 10.1200/JCO.21.01570. Epub 2021 Dec 20.