Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT II)

This is an interventional treatment trial for Metastatic Malignant Neoplasm Read More

Inclusion Criteria:

• Patients with metastatic cancer
• Patients may have received unlimited lines of prior therapy
• Prior to randomization, patients with metastatic disease must have been treated with established standard-of-care therapy, or physicians have determined that such established therapy is not sufficiently efficacious, or patients have declined to receive standard-of-care therapy
• The patient has measurable disease
• The patient has Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• The patient has biopsy-accessible tumor; for patients who had no prior anticancer therapy and had surgical resection within a year and tumor tissue is immediately available, that tumor will be analyzed and no biopsy will be needed
• Absolute neutrophil count >= 1,000/ul
• Platelets >= 100,000/ul (unless these abnormalities are due to bone marrow involvement)
• Total bilirubin level <= 1.5 x the upper limit of normal (ULN), unless the patient has known Gilbert's disease
• Alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase levels (SGPT) =< 2.5 X ULN (unless the patient has liver metastases)
• Serum creatinine clearance >= 50 ml/min by the Cockcroft-Gault formula
• If the patient has brain metastasis, they must have been stable (treated and/or asymptomatic) and the patient must have been off steroids for at least 2 weeks
• The patient has provided signed informed consent
• Patients with a previous malignancy (other than the patients' known cancer) that were treated successfully and are disease-free for at least 3 years are allowed
• Patients with a history of basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are eligible
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; childbearing potential will be defined as women who have had menses within the past 12 months and who have not had a tubal ligation, hysterectomy, or bilateral oophorectomy; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately
• Male subjects must agree to use effective contraception or abstinence while on study and for 90 days after last dose of study drug

Exclusion Criteria:

• Patients who are randomized to the control arm must not receive therapy based on prior molecular profiling
• The patient has received chemotherapy, surgery, or radiotherapy (for therapeutic purposes) within 3 weeks of initiating study treatment (4 weeks for bevacizumab or investigational drugs) or the patient has not recovered (grade >= 2 from side effects of the previous therapy); patients who receive palliative radiation therapy can be treated immediately after completion of radiation therapy
• The patient has cardiac conditions as follows: uncontrolled hypertension (blood pressure [BP] > 160/100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association class II or above), baseline left ventricular ejection fraction (LVEF) =< 50%, prior or current cardiomyopathy, atrial fibrillation with heart rate > 100 beats per minute (bpm), unstable ischemic heart disease (myocardial infarction [MI] within 6 months prior to starting treatment or angina requiring use of nitrates more than once weekly)
• The patient has peripheral neuropathy >= grade 2
• The patient is pregnant (confirmed by serum beta human chorionic gonadotropin [b-HCG], if applicable) or is breastfeeding
• The patient has concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease)
• The patient has refractory nausea and vomiting or chronic gastrointestinal diseases (e.g., inflammatory bowel disease) or has had significant bowel resection that would preclude adequate absorption (for oral therapy only)
• The patient is unable to swallow capsules and/or has a surgical or anatomical condition that precludes swallowing and absorbing oral medication on an ongoing basis (for oral therapy only)
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures