Clinical trial NCT03111901: Low-dose Interleukin-2 and Pembrolizumab in Melanoma and Renal Cell Cancer
Official title: Low-dose Interleukin-2 and Pembrolizumab Among Patients With Metastatic Melanoma and Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Renal Cell
Melanoma
Keywords: pembrolizumab
IL-2
interleukin-2
MK-3475
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2017-04-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and disease control rate of the combination of pembrolizumab plus low-dose interleukin-2 in patients who have either advanced melanoma or renal cell cancer.


Eligibility criteria: Main Inclusion Criteria

* Stage IV or unresectable stage III malignant melanoma or renal cell carcinoma.
* Melanoma

  * Patients must have failed anti-PD-1/PD-L1 antibody therapy.
  * Patients must have failed ipilimumab or be intolerant of ipilimumab and therefore unable to receive ipilimumab.
  * Patients may, but are not obligated, to have failed high- dose IL2.
  * 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.
  * Patients must have failed a VEGF pathway inhibitor and a second tyrosine kinase inhibitor.
  * Patients may, but are not obligated, to have failed high- dose IL2.
* Measurable disease based upon RECIST 1.1.
* 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: ECOG 0-1.
* Adequate organ function.
* Ability to provide informed consent.

Main Exclusion Criteria:

* Pregnancy
* 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. Replacement doses of steroids are permitted.
* Known history of active TB (Bacillus Tuberculosis)
* Hypersensitivity to pembrolizumab or any of its excipients.
* Known additional malignancies (exceptions DCIS or LCIS, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
* 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.
* 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.
* Known carcinomatous meningitis.
* Active autoimmune disease that has required systemic treatment in the past 2 years. 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.
* Active infection requiring systemic therapy.
* Known psychiatric or substance abuse disorders.
* Known history of Human Immunodeficiency Virus (HIV).
* Known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
* Has received a live vaccine within 30 days of planned start of study therapy.
* Severe chronic pulmonary disease.
* 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.
* History of (non-infectious) pneumonitis that required steroids or current pneumonitis.

Primary outcomes:
measure: Safety: adverse event profile
timeFrame: up to 90 days post-treatment
measure: Disease control rate: melanoma
timeFrame: baseline and every 9 weeks (up to week 104)
measure: Disease control rate: renal cell cancer
timeFrame: baseline and every 9 weeks (up to week 104)
Secondary outcomes:
measure: Progression free survival: metastatic melanoma
timeFrame: From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.
measure: Progression free survival: renal cell cancer
timeFrame: From first response (SD/PR/CR) to time of recurrence/progression or death from any cause, whichever occurs first, assessed for an estimated total of 120 months.
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
Study officials:
affiliation: University of Virginia Health System
name: William W Grosh, MD
role: PRINCIPAL_INVESTIGATOR
References: