Clinical Trials /

Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

NCT02748564

Description:

This study will evaluate the safety and tolerability of IL-2 when given in combination with pembrolizumab to patients with advanced melanoma. Aldesleukin may stimulate white blood cells to melanoma cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving aldesleukin and pembrolizumab may kill more tumor cells. There are two parts to this study: - Phase Ib: To determine the safety and side effects of increasing doses of IL-2 in combination with pembrolizumab - Phase II: Once the maximum tolerated dose of IL-2 is determined, additional patients will be treated to determine if it is effective against the cancer.

Related Conditions:
  • Cutaneous Melanoma
  • Melanoma of Unknown Primary
  • Mucosal Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma
  • Official Title: A Phase 1b/II Trial of Interleukin-2 in Combination With Pembrolizumab for Patients With Unresectable or Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: 091602
  • SECONDARY ID: NCI-2016-00466
  • SECONDARY ID: 091602
  • SECONDARY ID: P30CA072720
  • NCT ID: NCT02748564

Conditions

  • Metastatic Melanoma
  • Stage III Mucosal Melanoma of the Head and Neck
  • Stage IIIA Skin Melanoma
  • Stage IIIB Skin Melanoma
  • Stage IIIC Skin Melanoma
  • Stage IV Skin Melanoma
  • Stage IVA Mucosal Melanoma of the Head and Neck
  • Stage IVB Mucosal Melanoma of the Head and Neck
  • Stage IVC Mucosal Melanoma of the Head and Neck

Interventions

DrugSynonymsArms
Aldesleukin125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2Treatment (pembrolizumab, aldesleukin)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, aldesleukin)

Purpose

This study will evaluate the safety and tolerability of IL-2 when given in combination with pembrolizumab to patients with advanced melanoma. Aldesleukin may stimulate white blood cells to melanoma cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving aldesleukin and pembrolizumab may kill more tumor cells. There are two parts to this study: - Phase Ib: To determine the safety and side effects of increasing doses of IL-2 in combination with pembrolizumab - Phase II: Once the maximum tolerated dose of IL-2 is determined, additional patients will be treated to determine if it is effective against the cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine an optimal tolerated dose (OTD) of aldesleukin (interleukin [IL]-2) that is
      effective and tolerable in combination with pembrolizumab.

      II. To characterize the efficacy of the OTD of IL-2 in combination with pembrolizumab.

      SECONDARY OBJECTIVES:

      I. To characterize the safety of IL-2 in doses ranging up to the Food and Drug Administration
      (FDA)- approved dose when administered in combination with pembrolizumab.

      II. To characterize clinical endpoints, including overall survival, progression-free
      survival, and complete response rate.

      TERTIARY OBJECTIVES:

      I. To characterize immune parameters in the blood and tumor microenvironment and cellular and
      molecular features of the tumor tissue that correlate with response to combination therapy
      for study as potential predictive biomarkers.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 every 3 weeks and
      aldesleukin IV every 8 hours for up to 14 doses at weeks 4, 7, 16, 19, 28, and 31 in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months up to 10 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, aldesleukin)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1 every 3 weeks and aldesleukin IV every 8 hours for up to 14 doses at weeks 4, 7, 16, 19, 28, and 31 in the absence of disease progression or unacceptable toxicity.
  • Aldesleukin
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic or cytologic diagnosis of cutaneous melanoma, mucosal melanoma, or melanoma
             of unknown primary that is considered unresectable (stage III) or metastatic (stage
             IV)

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Have measurable disease evident on radiographs (preferred) or clinical examination;
             for this protocol, measurable disease is defined as at least one evaluable tumor that
             is at least 10 mm in longest dimension

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale

          -  Patients must have a brain magnetic resonance imaging (MRI) or computed tomography
             (CT) (with and without contrast) that is free of active metastases; metastases that
             have been treated with radiation or surgical resection, are stable for at least 4
             weeks and do not require steroids are eligible

          -  Normal cardiac function; patients who have a history of heart disease, or who are over
             the age of 50 years must have a normal cardiac stress test within the prior 90 days

          -  Normal lung function; patients who have extensive pulmonary metastases or any chronic
             pulmonary disease history must have pulmonary function testing demonstrating forced
             expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) > 65% of
             predicted values

          -  Absolute neutrophil count (ANC) >= 1,500 /mcL

          -  Platelets >= 100,000 / mcL

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO)
             dependency (within 7 days of assessment)

          -  Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated
             creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
             creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine
             levels > 1.5 X institutional ULN

          -  Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 ULN

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
             ULN OR =< 5 X ULN for subjects with liver metastases

          -  Albumin >= 2.5 mg/dL

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
             time (PTT) is within therapeutic range of intended use of anticoagulants

          -  Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication; if
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy

          -  Subject meets institutional requirements for IL-2 therapy

        Exclusion Criteria:

          -  Has primary ocular melanoma

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment

          -  Has a diagnosis of immunodeficiency or is receiving systemic immunosuppressive steroid
             therapy or any other form of systemic immunosuppressive therapy within 7 days prior to
             the first dose of trial treatment; exception: physiologic corticosteroid replacement
             therapy for adrenal or pituitary insufficiency is not considered systemic
             immunosuppressive steroid therapy

          -  Has received previous high dose IL-2 therapy, any programmed death (PD)-1 blocking
             antibody (e.g. pembrolizumab, nivolumab), or any programmed death ligand (PD-L)1
             blocking antibody in the metastatic setting; prior therapy with any PD-1 blocking
             antibody is allowed if given in the adjuvant setting and the last dose was > 6 months
             prior to study entry; prior therapy with ipilimumab is allowed (in the adjuvant or
             metastatic setting); other prior therapy (in the adjuvant or the metastatic setting)
             is allowed, including targeted therapy, chemotherapy, or experimental therapy

          -  Has a history of significant congestive heart failure or significant pulmonary disease

          -  Has a known history of active TB (bacillus tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at
             baseline) from adverse events due to a previously administered agent

               -  Note: subjects with =< grade 2 neuropathy and/or alopecia are exceptions to this
                  criterion and may qualify for the study

               -  Note: if subject received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting therapy

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment; this exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment

          -  Has known history of, or any evidence of active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Has received a live vaccine within 30 days of planned start of study therapy

               -  Note: seasonal influenza vaccines for injection are generally inactivated flu
                  vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist)
                  are live attenuated vaccines, and are not allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:15 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall response rate as assessed by Response Evaluation Criteria in Solid Tumors version 1.1, with the modification that progressive disease must be confirmed on a subsequent scan
Time Frame:Up to 36 weeks
Safety Issue:
Description:Estimated using OTD of IL-2 and pembrolizumab with 95% confidence interval with borders +/- 15%

Secondary Outcome Measures

Measure:Complete response rate
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Incidence of adverse events as evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0
Time Frame:Up to 30 days after last dose of treatment
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:Estimated using Kaplan-Meier curves
Measure:Progression-free survival
Time Frame:Up to 36 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rutgers, The State University of New Jersey

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