Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: R115777 in Treating Patients With Advanced Solid Tumors

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
  PURPOSE: Phase I trial to study the effectiveness of R115777 in treating patients who have advanced solid tumors.

Detailed description: OBJECTIVES:
  -  Determine the maximum tolerated dose of R115777 in patients with advanced malignant solid tumors.
  -  Assess the toxicity of this drug in these patients.
  -  Determine, preliminarily, the efficacy of this drug in these patients.
  -  Determine the potential predictors of response in patients treated with drug.
  OUTLINE: This is a multicenter, dose-escalation study.
  Patients receive oral R115777 twice daily on weeks 1 and 3. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
  Cohorts of 3-6 patients receive escalating doses of R115777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
  PROJECTED ACCRUAL: A minimum of 20 patients will be accrued for this study within 12 months.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed malignant tumors deemed to be incurable or refractory to therapy
  -  Advanced, recurrent, or metastatic disease
  -  Previously treated with at least 1 chemotherapy regimen
  -  Brain metastases allowed if asymptomatic and controlled (e.g., after prior surgical resection or radiotherapy/radiosurgery) and not on steroids or anticonvulsants
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  Karnofsky 60-100%
  Life expectancy:
  -  Not specified
  Hematopoietic:
  -  WBC at least 3,500/mm3
  -  Absolute granulocyte count at least 1,500/mm3
  -  Platelet count at least 75,000/mm3
  Hepatic:
  -  Bilirubin no greater than 2.5 times upper limit of normal (ULN)
  -  SGOT no greater than 2.5 times ULN
  Renal:
  -  Creatinine clearance at least 60 mL/min OR
  -  Creatinine no greater than 1.6 mg/dL
  Other:
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception during and for 3 months after study
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  No concurrent biologic therapy
  Chemotherapy:
  -  See Disease Characteristics
  -  At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea)
  Endocrine therapy:
  -  See Disease Characteristics
  -  No concurrent hormonal therapy
  Radiotherapy:
  -  See Disease Characteristics
  -  At least 4 weeks since prior radiotherapy and recovered
  -  No prior radiotherapy to a field containing a measurable target lesion unless there is evidence of progression or a new lesion is present
  -  No concurrent radiotherapy to measurable lesions
  Surgery:
  -  See Disease Characteristics
  -  At least 3 weeks since prior major surgery and recovered
  Other:
  -  At least 2 weeks since prior proton pump inhibitors (e.g., omeprazole)
  -  Concurrent H2 blockers (e.g., cimetidine or related drugs) or antacids are allowed if there is an interval of at least 2 hours between H2 blocker/antacid intake and R115777 dosing

Relevance to patient case: not relevant