Clinical Trials /

Anti-PD-1 Antibody With HD IL-2 in Metastatic Melanoma

NCT03476174

Description:

The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant melanoma. Response assessment will be performed after pembrolizumab therapy, and response reassessment will be performed after HD IL-2 therapy using revised RECIST 1.1.

Related Conditions:
  • Melanoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Anti-PD-1 Antibody With HD IL-2 in Metastatic Melanoma
  • Official Title: MMP-01: Pilot Study Evaluating Activity of the Combination of Anti-PD-1 Antibody With High Dose IL-2 in Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: HCRN-MMP-MEL16-261
  • NCT ID: NCT03476174

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPembrolizumab and HD Interleukin 2
Interleukin-2High Dose IL-2Pembrolizumab and HD Interleukin 2

Purpose

The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant melanoma. Response assessment will be performed after pembrolizumab therapy, and response reassessment will be performed after HD IL-2 therapy using revised RECIST 1.1.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab and HD Interleukin 2ExperimentalPembrolizumab 200 mg IV over 30 minutes; Day 1 of each cycle 3 weeks (21 days) for 2 cycles. IL-2 600,000 IU/kg2 IV over 15 minutes every 8 hours for up to 14 doses over 5 days; Days 1-5 = Cycle 1; 9 days of rest in between; Days 15-19 = Cycle 2
  • Pembrolizumab
  • Interleukin-2

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent and HIPAA authorization for release of personal health
             information prior to registration. NOTE: HIPAA authorization may be included in the
             informed consent or obtained separately.

          -  Age ≥ 18 years at the time of consent.

          -  ECOG Performance Status of 0-1 within 28 days prior to registration (Appendix 1).

          -  Life expectancy of 6 months or greater as determined by the site investigator.

          -  Histologically-confirmed diagnosis of unresectable stage IV or metastatic melanoma not
             amenable to local therapy.

          -  Measurable disease, defined as at least 1 tumor that fulfills the criteria for a
             target lesion according to RECIST 1.1 (Section 9), and obtained by imaging within 28
             days prior to registration for protocol therapy.

          -  < 2 lines of prior therapy for metastatic melanoma. Cannot have received prior therapy
             with HD IL-2. May have had one prior line of therapy that included a check point
             inhibitor.

          -  Prior systemic cancer treatment must be completed at least 21 days prior to first dose
             of study drug and the subject must have recovered from all reversible acute toxic
             effects of the regimen (other than alopecia or vitiligo) to Grade ≤ 1 or baseline.

          -  Not received radiation therapy within 21 days of initiation of study treatment, and
             the measurable disease must have been outside of the radiation port.

          -  Demonstrate adequate organ function. All screening labs to be obtained within 28 days
             prior to registration.

               -  WBC ≥ 3,000/L

               -  ANC ≥ 1,000/L

               -  Hgb ≥ 9g/dL

               -  Plt ≥ 100 × 10(9)/L

               -  Serum creatinine ≤ 1.5 mg/dL

               -  Calculated creatinine clearance ≥ 40 mL/min; if serum creatinine > 1.5 mg/dL

               -  Total Bilirubin ≤ 1.5 × upper limit of normal (ULN)

               -  Direct Bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN

               -  Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)≤ 2.5 × ULN or
                  ≤ 5 x ULN for subjects with known hepatic metastasis

               -  International Normalized Ratio (INR) ≤ 1.5 × ULN; For subjects receiving warfarin
                  or LMWH, the subjects must, in the site investigator's opinion, be clinically
                  stable with no evidence of active bleeding while receiving anticoagulant therapy.
                  The INR for these subjects may exceed 1.5 × ULN if that is the goal of
                  anticoagulant therapy.

          -  Adequate baseline pulmonary function test (PFT) (FEV1 > 2 L or ≥ 75% of predicted for
             height and age).

          -  Documented left ventricular ejection fraction (LVEF) of > 45%, testing is required in
             patients with:

               -  Age ≥ 60 years old

               -  Clinically significant atrial and or ventricular arrhythmias including but not
                  limited to: atrial fibrillation, ventricular tachycardia, second or third degree
                  heart block

               -  History of coronary revascularization or ischemic symptoms

          -  Archival tissue (from the primary tumor or metastases) is mandatory if available for
             correlative studies. If archived tumor tissue is not available, the patient does not
             need to undergo a biopsy to obtain tissue and is still eligible for study.

          -  Females of childbearing potential must have a negative serum pregnancy test within 3
             days prior to registration. NOTE: Females are considered of child bearing potential
             unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least
             12 consecutive months

          -  Females of childbearing potential and males must be willing to abstain from
             heterosexual activity or to use 2 forms of effective methods of contraception from the
             time of informed consent until 120 days after treatment discontinuation. The two
             contraception methods can be comprised of two barrier methods, or a barrier method
             plus a hormonal method.

          -  Male subjects who are not surgically sterile (vasectomy) must agree to use an adequate
             method of contraception. Male subjects with female sexual partners who are pregnant,
             possibly pregnant or who could become pregnant during the study must agree to use
             condoms from the first dose of study drug through 120 days after the last dose of
             study therapy. Total abstinence for the same study period is an acceptable
             alternative.

          -  As determined by the enrolling physician or protocol designee, ability of the subject
             to understand and comply with study procedures for the entire length of the study

          -  Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

        Exclusion Criteria:

          -  Active infection requiring systemic therapy

          -  Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study.

          -  Known additional malignancy that is active and/or progressive requiring treatment;
             exceptions include basal cell or squamous cell skin cancer, in situ cervical or
             bladder cancer, or other cancer for which the subject has been disease-free for at
             least five years.

          -  Active central nervous system (CNS) metastases. NOTE: if prior metastasis but treated
             and clinically stable for 1 month after treatment are eligible. Subjects with 3 or
             fewer brain metastases that are less than 1 cm in diameter and asymptomatic are
             eligible.

          -  Surgery within 4 weeks prior to study treatment except for minor procedures. NOTE:
             Hepatic biliary stent placement is allowed.

          -  Uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg
             diastolic for > 4 weeks) despite standard medical management.

          -  Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to
             initiation of study treatment.

          -  Any Grade 3-4 GI bleeding within 3 months prior to initiation of study treatment.

          -  History of deep vein thrombosis, pulmonary embolism, or any other significant
             thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis
             are not considered "significant") during the 3 months prior to initiation of study
             treatment.

          -  Any arterial thromboembolic events, including but not limited to myocardial
             infarction, transient ischemic attack, cerebrovascular accident, or unstable angina,
             within 6 months prior to initiation of study treatment.

          -  Gross hemoptysis within 2 months of initiation of study treatment.

          -  Has any condition that, in the opinion of the investigator, might jeopardize the
             safety of the patient or interfere with protocol compliance.

          -  Has any mental or medical condition that prevents the patient from giving informed
             consent or participating in the trial.

          -  Known hypersensitivity to pembrolizumab or IL-2 or any of their components.

          -  Known history of active tuberculosis.

          -  Concurrent systemic steroid therapy with doses above physiologic level.

          -  History of autoimmune disease, including but not limited to myasthenia gravis,
             myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
             inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid
             syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré
             syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.

               -  Subjects with a history of autoimmune-related hypothyroidism on a stable dose of
                  thyroid replacement hormone may be eligible for this study.

               -  Subjects with controlled Type I diabetes mellitus on a stable dose of insulin
                  regimen may be eligible for this study.

               -  Subjects with a history of celiac disease may be eligible if controlled with
                  diet.

          -  Treatment with any investigational agent within 21 days prior to initiation of study
             treatment and the subject must have recovered from the acute toxic effects of the
             regimen.

          -  Prior organ transplant including allogeneic transplantation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate
Time Frame:12 months
Safety Issue:
Description:Assess the response rate [complete response (CR) + partial response (PR)] of sequential therapy of pembrolizumab followed by HD IL-2 in subjects with stage IV malignant melanoma. Response assessment will be performed using revised RECIST 1.1

Secondary Outcome Measures

Measure:Assess Adverse Events
Time Frame:12 months
Safety Issue:
Description:Assess adverse events via CTCAE v4.03
Measure:Progression Free Survival (PFS)
Time Frame:12 months
Safety Issue:
Description:Measure Progression-Free Survival (PFS) using revised RECIST guideline (version 1.1) after completion of 2 cycles of pembrolizumab and 2 cycles of HD IL-2 in all the subjects enrolled in the study. PFS is defined as the time from treatment initiation until objective tumor progression or death.
Measure:Overall Survival (OS)
Time Frame:12 months
Safety Issue:
Description:Measure overall survival (OS) at 12 months in subjects with stage IV malignant melanoma who showed a response [stable disease (SD), complete response (CR) or partial response (PR)] following completion of 2 cycles of pembrolizumab and 2 cycles of HD IL-2. OS is defined as time from treatment initiation until death from any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ralph Hauke

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