Aldesleukin and Pembrolizumab in Treating Participants with Stage III and IV Melanoma and Renal Cell Cancer
This phase I / II trial studies the side effects and how well pembrolizumab and aldesleukin work in treating participants with stage III and IV melanoma or renal cell cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Interleukins, such as aldesleukin, are proteins made by white blood cells and other cells in the body and may help regulate immune response. Giving pembrolizumab and aldesleukin may work better in treating melanoma and renal cell cancer.
- In order to be eligible for participation in this trial, the subject must have stage IV or unresectable stage III malignant melanoma or renal cell carcinoma.
- Melanoma: Patients must have failed anti-programmed cell death protein (PD) - 1/PD-ligand (L) 1 antibody therapy.
- Melanoma: Patients must have failed ipilimumab or be intolerant of ipilimumab and therefore unable to receive ipilimumab.
- Melanoma: Patients may, but are not obligated, to have failed high-dose interleukin-2 (IL2).
- Melanoma: BRAF status must be known or unable to be performed. If the melanoma expresses a BRAF mutation of V600E, V600K, or V600R patient must have received and progressed through a BRAF inhibitor or have failed that therapy due to toxicity.
- Renal cell carcinoma: Patients must have failed anti-PD-1/PD-L1 antibody therapy.
- Renal cell carcinoma: Patients must have failed a VEGF pathway inhibitor and a second tyrosine kinase inhibitor.
- Renal cell carcinoma: Patients may, but are not obligated, to have failed high- dose IL2.
- Measurable disease based upon Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as defined by having at least 1 lesion accurately measured in at least 1 dimension, which is at least 20 mm by physical exam techniques, or at least 10 mm by spiral computed tomography (CT) scan. Note: Lesions considered intrinsically non-measurable include: Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion, lesions situated in a previously irradiated area.
- Subjects with brain metastases will be eligible if the following are true: * Subjects with =< 3 brain metastases. ** All metastases are =< 3 cm. ** All metastases have been treated and are asymptomatic. ** Steroids are not required for management of the brain metastases. ** All metastases have been stable for 1 month following treatment. * Subjects with > 3 brain metastases. ** All metastases are =< 3 cm. ** All metastases have been treated and are asymptomatic. ** Steroids are not required for management of the brain metastases. ** All metastases have been stable for 6 months following treatment.
- Performance status: Eastern Cooperative Oncology Group (ECOG) 0-1.
- Pathology reviewed at the University of Virginia histologically or cytologically confirmed malignant melanoma or renal cell carcinoma.
- Be willing and able to provide written informed consent/assent for the trial.
- Absolute neutrophil count (ANC) >= 1,500/mcL (performed within 10 days of treatment initiation).
- Platelets >= 100,000/mcL (performed within 10 days of treatment initiation).
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation).
- 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 (performed within 10 days of treatment initiation).
- Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN. Patients with Gilbert’s disease may be eligible if bilirubin < 3.0 (performed within 10 days of treatment initiation).
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for subjects with liver metastases.
- Albumin >= 2.5 mg/dL (performed within 10 days of treatment initiation).
- 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 (performed within 10 days of treatment initiation).
- 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 (performed within 10 days of treatment initiation).
- 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 must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects of childbearing potential 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. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- 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 primary or secondary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 3 weeks prior to the first dose of trial treatment. Note, however, that patients who are taking steroids at replacement doses (eg after adrenal insufficiency or pituitary deficiency after prior ipilimumab therapy) are not excluded.
- Has a known history of active TB (Bacillus Tuberculosis).
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include carcinoma in situ of the breast (ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS]), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 3 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 3 weeks earlier. Stable toxicity, however, may be accepted as long as no additional immunosuppressive therapy is needed (e.g. hypothyroidism after prior immune therapy, hypophysitis with loss of pituitary gland, stable clinically on replacement therapy).
- 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 known carcinomatous meningitis.
- 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients may be eligible if they have the following autoimmune diseases: thyroiditis or hypothyroidism, mild arthritis, diabetes, resolved hypophysitis, ulcerative colitis after total abdominal colectomy.
- 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 virus 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.
- Has had myocardial infarction within the past 6 months.
- Has severe chronic pulmonary disease.
- Has congestive heart failure, angina, or symptomatic cardiac arrhythmia or is classified according to the New York Heart Association classification as having Class III or IV heart disease.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Locations & Contacts
Status: Temporarily closed to accrual
Contact: William Wangerin Grosh
Trial Objectives and Outline
I. To obtain data on the safety of administration of pembrolizumab plus subcutaneous (SC [SQ]) low dose (LD) - aldesleukin (interleukin-2) [IL2]). (Safety)
II. To estimate the disease control rate (complete response [CR] + partial response [PR] + stable disease [SD] by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) among candidate patients with metastatic melanoma treated with pembrolizumab and SQ LD-IL2 and to determine whether disease control is significantly improved from an assumed null rate of 20%. (Clinical)
III. To estimate the disease control rate (CR + PR + SD by RECIST 1.1) among candidate patients with renal cell carcinoma treated with pembrolizumab and SQ LD-IL2 and to determine whether disease control is significantly improved from an assumed null rate of 30%. (Clinical)
I. To estimate progression free survival among candidate patients with metastatic renal cell carcinoma.
II. To estimate progression free survival among candidate patients with metastatic melanoma.
Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 2 of course 1 and day 1 of subsequent courses. Participants also receive aldesleukin SC on days 1-5 and 8-12. Courses repeat every 21 days for up to 2 years.
After completion of study treatment, participants are followed up at 30 days, every 12 weeks for up to 2 years, then annually thereafter.
Trial Phase & Type
University of Virginia Cancer Center
William Wangerin Grosh
Secondary IDs NCI-2018-01718, Am 002
Clinicaltrials.gov ID NCT03111901