Clinical Trials /

IL2 With Ipilimumab Followed by Nivolumab in Stage 3 or 4 Melanoma Patients

NCT04562129

Description:

The purpose of this study is to find out if the administration of Interleukin-2 concurrently with ipilimumab followed by Nivolumab will result in improved anti-cancer activity and if it is effective for advanced melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ph 2 Study of IL2 With Ipilimumab Followed by Nivolumab in Stage 3 or 4 Melanoma Patients
  • Official Title: A Phase II Study of High Dose Bolus IL2 in Combination With Low Dose Ipilimumab Followed Sequentially by Nivolumab in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy

Clinical Trial IDs

  • ORG STUDY ID: MCC-20494
  • SECONDARY ID: CIIT19PLK13
  • NCT ID: NCT04562129

Conditions

  • Melanoma Stage III
  • Melanoma Stage IV
  • Inoperable Disease

Interventions

DrugSynonymsArms
Interleukin-2AldesleukinTreatment
IpilimumabTreatment
NivolumabTreatment

Purpose

The purpose of this study is to find out if the administration of Interleukin-2 concurrently with ipilimumab followed by Nivolumab will result in improved anti-cancer activity and if it is effective for advanced melanoma.

Detailed Description

      This is a Phase II study of high dose bolus interleukin-2 (HD IL2) in combination with low
      dose ipilimumab followed sequentially by nivolumab in patients with advanced inoperable stage
      III or stage IV melanoma who have failed prior anti-PD1 immunotherapy.

      The planned treatment consists of 3 courses (One cycle is 21 days and one course is 4
      cycles). HD IL2 will be given during week 1 of the 2 initial cycles or each course.
      Ipilimumab will be given concurrently at the low dose of 1 mg/kg on Day 1 of the 2 initial
      cycles of each course for up to 2 doses, total. Nivolumab will be given on Day 1 of the 3rd
      cycle of each course. No systemic treatment will be administered during the 4th cycle.
      Response assessment will occur at the end of the 4th cycle. Patients without evidence of
      disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses
      of treatment for up to a maximum of 3 courses, total
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalHD IL2 (600,000 units/kg/dose IV) will be given during week 1 of the 2 initial cycles or each course. Ipilimumab will be given concurrently at the low dose of 1 mg/kg on Day 1 of the 2 initial cycles of each course for up to 2 doses, total. Nivolumab will be given on Day 1 of the 3rd cycle of each course. No systemic treatment will be administered during the 4th cycle. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities will be offered additional courses of treatment for up to a maximum of 3 courses, total.
  • Interleukin-2
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed metastatic melanoma. This includes American
             Joint Committee on Cancer (AJCC) stage IV or advanced/inoperable stage III. This also
             includes patients with a history of lower stage melanoma and subsequent recurrent
             metastatic disease that is either locally/regionally advanced/inoperable disease or
             distant metastases

          -  Measurable disease, according to RECIST version 1.1

          -  Must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4
             weeks prior to enrollment. If known to have prior brain metastases, these must have
             been adequately managed with standard of care radiation therapy, stereotactic
             radiosurgery or surgery prior to registration on the study.

          -  Must have previously received anti-PD1 immunotherapy (nivolumab or pembrolizumab) and
             later experienced disease progression, within 3 months of registration on this study.

          -  Must not have received systemic therapy or radiotherapy within the preceding 3 weeks.
             Patients must have recovered from adverse events from previous therapy by the time
             registration.

          -  Must be at least 4 weeks from major surgery and have fully recovered from any effects
             of surgery, and be free of significant detectable infection prior to registration.

          -  Patients who have received prior anti-CTLA4 monoclonal antibody therapy (ipilimumab or
             tremelimumab) are eligible.

          -  Patients with BRAF V600 mutant melanoma must have previously received BRAF targeted
             therapy for metastatic melanoma and later experienced disease progression. Patients
             who refuse to receive BRAF targeted therapy or were intolerant of BRAF targeted
             therapy are eligible.

          -  Life expectancy of greater than 3 months in the opinion of the investigator

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Must have normal organ and marrow function as specified per protocol.

          -  Patients on full-dose anticoagulants with Prothrombin Time Test International
             Normalized Ratio (PT INR) >1.5 are eligible provided that both of the following
             criteria are met: (a) The patient has an in-range INR (usually between 2 and 3) on a
             stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.
             (b) The patient has no active bleeding or pathological condition that carries a high
             risk of bleeding (e.g., tumor involving major vessels or known varices).

          -  Pulmonary: Forced Expiratory Volume at 1 second (FEV1) > 2.0 liters or > 75% of
             predicted for height and age. Pulmonary function tests (PFTs) are required for
             patients over 50 years old or with significant pulmonary or smoking history

          -  No evidence of congestive heart failure, symptoms of coronary artery disease,
             myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias,
             or unstable angina.

          -  Patients who are over 40 years old or have had previous myocardial infarction greater
             than 6 months prior to study entry or have significant cardiac family history (CAD or
             serious arrhythmias) will be required to have a negative or low probability cardiac
             stress test (for example, thallium stress test, stress multigated acquisition scan
             (MUGA), stress echo or exercise stress test) for cardiac ischemia within 8 weeks prior
             to registration.

          -  No history of cerebrovascular accident or transient ischemic attacks within the past 6
             months from registration.

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for
             the duration of study participation, and for at least 6 months after completion of
             study therapy. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her treating physician immediately.

          -  Women should not be lactating and, if of childbearing age, should have a negative
             pregnancy test (b-HCG test; serum or urine, minimum sensitivity 25 IU/L or equivalent
             units of b-HCG) within two weeks of registration in the study.

        Exclusion Criteria:

          -  Patients who have had systemic therapy for melanoma or radiotherapy within 3 weeks
             prior to registering on the study or those who have not recovered from adverse events
             due to agents administered more than 3 weeks earlier. Patients with a history of
             endocrinopathies (e.g. hypothyroidism, adrenal insufficiency, hypopituitarism) are
             eligible if they are stable on hormone replacement therapy.

          -  Patients may not be receiving any other investigational agents.

          -  Patients with active brain metastasis are excluded

          -  Patients with clinically significant cardiovascular or cerebrovascular disease

          -  PT INR >1.5 unless the patient is on full-dose warfarin.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients who have other current malignancies are not eligible. Patients with other
             malignancies are eligible if they have been continuously disease free for > 2 years
             prior to the time of registration. Patients with prior history at any time of any in
             situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ,
             atypical melanocytic hyperplasia or melanoma in situ are eligible. Patients with prior
             history of basal or squamous skin cancer are eligible. Patients who have had multiple
             primary melanomas are eligible.

          -  Patients must not have autoimmune disorders or conditions of immunosuppression that
             require current ongoing treatment with systemic corticosteroids (or other systemic
             immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or
             continuous use of topical steroid creams or ointments or ophthalmologic steroids or
             steroid inhalers. If a patient had been taking steroids, at least 2 weeks must have
             passed since the last dose. Patients stable on physiologic replacement doses of
             steroids or other forms of hormone replacement therapy are eligible.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate
Time Frame:Up to 9 months
Safety Issue:
Description:Response rate (Complete Response + Partial Response) of HD IL2 plus low dose ipilimumab followed sequentially by nivolumab in patients with inoperable stage III or stage IV melanoma who have either failed prior treatment with anti-PD1 immunotherapy (nivolumab or pembrolizumab) or have demonstrated tumor progression following such therapy.

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Progression Free Survival (PFS) is defined as the duration of time from start of treatment to time of progression (or death if there is no progression date). Patients with neither a progression date nor date of death will be censored as of last contact.
Measure:Overall Survival
Time Frame:Up to 5 years
Safety Issue:
Description:Overall Survival (OS) will be measured from the initial date of treatment to the recorded date of death.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • skin cancer

Last Updated

September 18, 2020