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Clinical Trial 18345

Cancer Type: Genitourinary
Study Type: Treatment
NCT#: NCT02298959

Phase: Phase I
Prinicipal Investigator:

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Study Title

A Phase 1 Trial of MK-3475 Plus Ziv-Aflibercept in Patients with Advanced Solid Tumors


The purpose of this study is to test the safety of MK-3475 along with ziv-aflibercept, given by vein, at different doses to find out what effects, if any, it has on participants.


To determine the safety, tolerability and recommended phase II dosing for the combination of ziv-aflibercept plus MK-3475 in patients with unresectable stage III or stage IV melanoma, renal cell cancer, ovarian cancer, or colorectal cancer.




MK-3475 (Keytruda); Ziv-aflibercept ()

Inclusion Criteria

  • In dose escalation, must have histologically or cytologically confirmed metastatic disease from any solid tumor; in dose expansion, must have histologically or cytologically confirmed metastatic melanoma, renal cell carcinoma, ovarian cancer, or colorectal cancer
  • Renal cell participants must have had at least one prior vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI)
  • Ovarian cancer participants must be resistant to platinum therapy
  • No more than two prior therapies for metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky >= 70%)
  • Estimated life expectancy of greater than 6 months
  • Adequate hematologic, hepatic and renal function
  • International normalized ratio (INR) or prothrombin time (PT) less than or equal to 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) less than or equal to 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
  • Archival tissue must be available or newly obtained core or excisional biopsy of a tumor lesion
  • Must have measurable disease based on RECIST 1.1
  • Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation
  • WOCBP should have a negative urine or serum pregnancy test within 24 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
  • Ability to understand and the willingness to sign a written informed consent document

  • Exclusion Criteria

  • Have had chemotherapy, targeted small molecule therapy, or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Note: patients with equal to or less than grade 2 neuropathy are an exception and may qualify for the study. Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Currently participating in or have participated in a study of an investigational agent or using 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 had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., => Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
  • Known gastrointestinal metastases
  • Ulcerated skin lesions
  • Need for full anti-coagulant therapy
  • Poorly-controlled hypertension
  • Women who are pregnant or nursing
  • Known brain metastases
  • Carcinomatous meningitis
  • Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 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
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 and ziv-aflibercept
  • Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents; patients with vitiligo or resolved childhood asthma/atopy would be an exception; patients that require intermittent use of bronchodilators or local steroid injections would not be excluded; patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's 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
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or ziv-aflibercept (prior treatment with bevacizumab is not an exclusion criteria)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit study compliance
  • Patients who are human immunodeficiency virus (HIV) positive may be eligible if they meet specific criteria
  • Known active hepatitis B or hepatitis C
  • Received live vaccine within 30 days prior to first dose of trial treatment

  • If you are interested in learning more about clinical trials, our clinical trial navigators can discuss your options and recommend opportunities that may be suitable for you. Call 813-745-6100 or 1-800-679-0775 (toll-free) or submit a clinical trials inquiry form.