Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: MS-275 in Treating Patients With Advanced Solid Tumors or Lymphoma

Summary: RATIONALE: MS-275 may stop the growth of cancer cells by blocking the enzymes necessary for their growth.
  PURPOSE: This phase I trial is studying the side effects and best dose of MS-275 in treating patients with advanced solid tumors or lymphoma.

Detailed description: OBJECTIVES:
  -  Determine the dose-limiting toxicity and maximum tolerated dose of MS-275 in patients with advanced solid tumors or lymphomas.
  -  Determine the profile of adverse events, including changes in laboratory parameters, in patients treated with this drug.
  -  Assess the pharmacology and pharmacokinetics of this drug in these patients.
  -  Design MS-275 regimens with possibly more frequent dose administration based on the pharmacology of MS-275 using the schedule in this study.
  -  Determine the antineoplastic activity of this drug in these patients.
  OUTLINE: This is an open-label, dose-escalation study.
  Patients receive oral MS-275 once on day 1. Courses repeat every 2 weeks (every 2-week schedule). Alternatively, patients receive oral MS-275 once on days 1, 8, 15, and 22 (weekly schedule). Courses repeat every 6 weeks. Treatment for both schedules continues in the absence of disease progression or unacceptable toxicity.
  Cohorts of 3-6 patients receive escalating doses of MS-275 on the every 2-week schedule until the maximum tolerated dose (MTD) is determined. Once the MTD for the every 2-week schedule is determined, patients receive treatment on the weekly schedule as above. The MTD is then determined for the weekly schedule. The MTD for both schedules is defined as the dose preceding that at which at least 2 of up to 6 patients experience dose-limiting toxicity. Once the MTD is determined for the weekly schedule, up to 3 additional patients are accrued to receive MS-275 at the MTD of the weekly schedule.
  Disease status is assessed every 3 months.
  PROJECTED ACCRUAL: A total of 50-75 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed malignancy that is metastatic or unresectable and for which no effective standard curative or palliative therapy exists
  -  Brain metastases allowed provided both of the following criteria are met:
  -  Received treatment for the brain metastases
  -  Stable for ≥ 6 months without steroids or antiseizure medications
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  ECOG 0-2 OR
  -  Karnofsky 50-100%
  Life expectancy:
  -  More than 3 months
  Hematopoietic:
  -  WBC at least 3,000/mm^3
  -  Absolute neutrophil count at least 1,500/mm^3
  -  Platelet count at least 100,000/mm^3
  Hepatic:
  -  Bilirubin no greater than 1.5 times upper limit of normal (ULN) (≤ 3 mg/dL for patients with Gilbert's syndrome)
  -  AST/ALT no greater than 2.5 times ULN
  -  Albumin at least 75% of lower limit of normal
  Renal:
  -  Creatinine normal OR
  -  Creatinine clearance at least 60 mL/min
  Cardiovascular:
  -  Cardiac ejection fraction normal by MUGA
  -  No symptomatic congestive heart failure
  -  No unstable angina pectoris
  -  No cardiac arrhythmia
  Other:
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  Adequate oral intake
  -  No weight loss of more than 10% of actual body weight within the past 2 months
  -  No history of allergic reaction to compounds of similar chemical or biological composition to study drug
  -  No other uncontrolled illness
  -  No ongoing or active infection
  -  No seizure disorder
  -  No psychiatric illness or social situation that would preclude study compliance
  -  No acute or chronic gastrointestinal conditions (e.g., peptic ulcer or colitis) within the past 2 months that would interfere with drug tolerance or absorption
  -  Willing and able to self-administer and document doses of MS-275
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  At least 4 weeks since prior anticancer vaccine therapy and recovered
  -  No concurrent immunotherapy
  Chemotherapy:
  -  At least 4 weeks since prior anticancer chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  -  At least 8 weeks since prior UCN-01 and recovered
  -  No concurrent chemotherapy
  Endocrine therapy:
  -  At least 4 weeks since prior anticancer hormonal therapy (except gonadotropin-releasing hormone [GnRH] agonists) and recovered
  -  Concurrent corticosteroids for physiological replacement, as antiemetic therapy, or for an ongoing condition allowed
  -  Must be on a stable dose during the past 4 weeks
  -  No concurrent anticancer hormonal therapy except GnRH agonists for noncastrated patients with prostate cancer
  Radiotherapy:
  -  At least 4 weeks since prior anticancer radiotherapy and recovered
  -  No concurrent radiotherapy
  -  Concurrent localized radiotherapy to a single lesion allowed if the patient achieves at least a partial response
  Surgery:
  -  At least 3 weeks since prior major surgery
  Other:
  -  No other concurrent investigational or commercial antineoplastic therapies

Relevance to patient case: not relevant