Clinical Trial 21755

• Overview

  Study Title:

  A phase II study of lenvatinib plus everolimus versus cabozantinib in patients with metastatic renal cell carcinoma that progressed on a PD-1/PD-L1 checkpoint inhibitor (LenCabo)

  Objective:

  Primary Objective: To compare the efficacy of lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor. Secondary Objectives: To compare tumor responses to lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor. To compare health-related quality of life (HRQoL) and safety of lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor. To compare overall survival (OS) with lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor.

• Treatments

  Therapies:

  Chemotherapy (NOS); Therapy (NOS)

  Medications:

  Cabozantinib (XL 184); E7080 (Lenvatinib); Lenvatinib (Lenvima); everolimus (RAD001)

• Inclusion Criteria

  Inclusion criteria:
  • Patients with histologically or cytologically confirmed metastatic/advanced clear cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior lines of systemic treatment in the advanced or metastatic setting, including a PD-1/PD-L1 checkpoint inhibitor. Patients who received a PD-1/PD-L1 checkpoint inhibitor in the adjuvant setting are permitted as long as their last dose of therapy was within the past 6 months.
  • Must have previously progressed on or after treatment (at any point after completing prior therapy) with a PD-1/PD-L1-containing regimen. Patients who experienced an immune-mediated adverse event related to their PD-1/PD-L1 containing-regimen and cannot receive additional PD-1/PD-L1 checkpoint inhibitor are permitted, without evidence of progression, if the treating physician intends to change treatment per standard care.
  • Must have at least one measurable site of disease per RECIST version 1.1. This is defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). For non-lymph node tumor lesions, they must be a minimum size of ≥ 10 mm. For malignant lymph node lesions, they must be at least ≥ 15 mm in short axis with conventional techniques or ≥ 10 mm with more sensitive techniques such as MRI or spiral CT scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
  • ECOG performance status less than or equal to 2
  • Age greater than or equal to 18 years
  • Patients must have adequate organ and marrow function prior to study entry as defined in protocol.
  • Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) before study entry. Pregnancy test must be repeated if performed > 14 days before starting study drug. 9. Women must not be breastfeeding. 10. Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy. 11. Patients with treated/stable brain metastases are allowed on protocol if they had brain metastases that received CNS-directed therapy, such as surgery or treatment with radiosurgery or Gamma knife, without recurrence or edema for at least 1 month (4 weeks).
  • Other criteria may apply

• Exclusion Criteria

  Exclusion criteria:
  • Prior receipt of lenvatinib, a c-MET inhibitor, such as cabozantinib or sitravatinib, or an mTOR inhibitor, such as everolimus or temsirolimus.
  • Must not have any other malignancies within the past 3 years except for in situ carcinoma of any site, adequately treated (without recurrence post-resection or postradiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but are not limited to: urothelial cancer grade Ta/T1 or adenocarcinoma of the prostate treated with active surveillance.
  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks (14 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded. Also, patients who have completed palliative radiation therapy more than 14 days prior to the first dose of lenvatinib plus everolimus or cabozantinib are eligible.
  • Patients who had a major surgery or significant traumatic injury (injury requiring > 28 days to heal) within 28 days of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that are expected to require major surgery during the course of the study.
  • Active inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  • Immunocompromising conditions, as follows: (a) Known acute or chronic human immunodeficiency virus (HIV) infection with CD4+ Tcell count 350 cells/µL and have not had an AIDS-defining infection within prior 12 months. If patients are on antiretroviral therapy (ART), it must be started at least 4 weeks prior to trial enrollment and the HIV viral load should be > Any underlying medical condition, which in the opinion of the Investigator, will make the administration ofstudy drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea, uncontrolled nausea, vomiting, malabsorption syndrome or small bowel resection that may significantly alter the absorption of lenvatinib, everolimus, or cabozantinib.
  • Patients receiving any concomitant systemic therapy for renal cell cancer are excluded.
  • Patients must not be scheduled to receive another experimental drug while on thisstudy.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Other criteria apply

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