Interleukin-2 and Pembrolizumab for Metastatic Kidney Cancer
Condition: Kidney Cancer
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell
Intervention: Pembrolizumab; Interleukin-2
Intervention description: Pembrolizumab: 200 mg every 3 weeks, 12 doses planned. This is considered the investigational part of the combination. The infusion time is 1 hour.; Interleukin-2: 8 admissions to hospital, each with 5 doses planned. This is considered the standard part of the combination. The standard interleukin-2 dose is 600,000 international units per kilogram per dose, with a maximum of 66,000,000 (for patients over 110 kg, which is 242 pounds). The dose is usually set at the start of the treatment and not adjusted. The infusion time is 15 minutes.
Intervention MeSH terms: Aldesleukin; Pembrolizumab; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney Disease; Metastatic; Antibody

Summary:

      The main purpose of this study is to evaluate the effects of the interleukin-2 given in
      combination with pembrolizumab.

      Interleukin-2 (IL-2) is also called aldesleukin, or Proleukin™.

      Pembrolizumab is also called Keytruda™, or anti-PD-1 antibody.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis/Condition for Entry into the Trial: Metastatic kidney cancer. Clear cell
             histology component from primary or metastatic lesion.

          -  Willing and able to provide written informed consent for the trial.

          -  Age over 18 on day of signing informed consent.

          -  Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
             1.1.

          -  Willing to provide tissue from a newly obtained or archival tissue, if available.

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          -  Demonstrate adequate organ function, as outlined in Table 1 of study protocol
             document.

          -  Females of childbearing potential must 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.

          -  Females of childbearing potential must agree 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.

          -  Males must 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.

          -  Cardiac testing with either exercise stress test or thallium stress test, within 3
             months of start of the first treatment day. Atrial fibrillation that is rate
             controlled is allowed. Note - the first treatment day is about 9 weeks before the
             first IL-2 treatment day. If a cardiologist's evaluation determines that this is
             superfluous based on other assessments, then this may be omitted.

          -  Pulmonary function test is required, within 3 months of start.

        Exclusion Criteria:

          -  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 steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          -  Has a known history of active Bacillus Tuberculosis (TB).

          -  Has hypersensitivity to pembrolizumab or any of its excipients.

          -  The number of prior therapies is restricted as follows: (a) Zero or one prior
             therapies during the preceding one year. This serves to limit the treatment cohort to
             patients with either only slowly progressive disease, or up to one prior therapy. (b)
             No prior PD-1 or PD-L1 antibody therapies are allowed. (c) Prior IL-2 is allowed, if
             it finished more than 1 year prior. (d) The following are not counted as medical
             therapies: nephrectomy, radiation therapy, other energy-ablative techniques, or
             metastasectomy.

          -  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 are an exception 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. Potential participants 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 that would be exclusionary.

          -  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 participation for the
             full duration of the trial, or is not in the best interest of the patient 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 received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., hepatitis C
             virus (HCV) 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.

          -  Myocardial infarction, stroke, coronary artery bypass surgery, coronary stent, or
             unstable angina within one year.