Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

Summary: The purpose of this study is to evaluate how effective Sunitinib works in treating acral lentiginous and mucosal melanoma which has spread beyond the local region. Suninitib is a protein-tyrosine kinase inhibitor and acts as a c-kit inhibitor drug. It is believed to work by blocking signals on certain cancer cells which allow the malignant cells to multiply and spread due to a change in the genetic make up of the cancer cell.

Detailed description: OBJECTIVES:
  Primary
  -  To determine the proportion of participants with metastatic mucosal or acral/lentiginous melanoma who are alive and without disease progression at two months after beginning treatment with sunitinib.
  -  To determine the best overall response rate.
  Secondary
  -  To determine the time to progression and overall survival.
  -  To correlate c-kit mutational status with response to therapy.
  -  To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
  -  To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.

Eligibility: Inclusion Criteria:
  -  History of primary mucosal or acral/lentiginous melanoma
  -  Histologically documented stage III unresectable or IV metastatic melanoma
  -  ECOG Performance Status 0,1 or 2
  -  Estimated life expectancy of 6 months or greater
  -  18 years of age or older
  -  Lab values as outlined in protocol
  -  Tumor blocks or slides must be available of either primary or metastatic tumor site for c-kit mutation testing
  -  Negative pregnancy test within 48 hours of starting treatment
  -  At least one measurable site of disease as defined by at least 1cm in greatest dimension
  Exclusion Criteria:
  -  Severe and/or uncontrolled medical disease
  -  Pregnant or nursing mothers
  -  Known brain metastasis. History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan
  -  Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or cervical carcinoma in situ
  -  Grade III/IV cardiac problems as defined by the New York Heart Association Criteria
  -  Ongoing cardiac dysrhythmias of grade 2 or greater, atrial fibrillation, QTc interval >450msec for males of >470 msec for females
  -  Hypertension that cannot be controlled by medication
  -  Any of the following within 12 months prior to starting treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
  -  NCI CTCAE version 3.0 grade 3 hemorrhage within 4 weeks of starting the study treatment
  -  Concurrent treatment with warfarin
  -  Prior treatment with SU011248 or any other antiangiogenic agent
  -  No H2 blockers or proton pump inhibitors
  -  Known chronic liver disease
  -  Known HIV infection
  -  Previous radiotherapy to 25% or more of the bone marrow and/or radiation therapy within 4 weeks prior to study entry
  -  Major surgery within 4 weeks prior to study entry
  -  Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication

Relevance to patient case: not relevant