This randomized clinical trial studies how molecular profiling and targeted therapy work in
treating patients with cancer that has spread to other places in the body compared to
standard treatment. Information about genetic differences in a patient's tumor can be used to
choose treatment that may target the tumor. It is not yet validated whether selecting
treatment after studying the genetic changes that are associated with cancer in a patient's
tumor is a better way to treat patients with metastatic cancer compared to therapy not based
on studying the genetic changes that are associated with cancer.
I. To determine whether patients treated with a matched targeted therapy selected on the
basis of genomic alteration analysis of the tumor have longer progression-free survival from
the time of randomization than those whose treatment is not selected on the basis of
alteration analysis.
OUTLINE: After completion of molecular profiling, patients who qualify for the trial will be
offered randomization as previously. If they wish to be randomized, patients will be
randomized to one of the two arms: matched targeted therapy (ARM I) or other therapy (ARM
II). Patients who decline to be randomized will then be offered their choice of the two trial
arms.
ARM I: Matched targeted therapy: Molecular profiling results are used to assign targeted
therapy. Patients receive targeted therapy by participating in a Phase I or a Phase II
clinical trial. If a clinical trial is not available, and a commercially available targeted
therapy exists (Food and Drug Administration [FDA]-approved for another indication), patients
can receive the FDA-approved drug.
ARM II: Other therapy: Patients receive standard of care therapy at the discretion of the
treating physician.
Patients with tumor progression who achieve the primary study endpoint can cross over to the
other treatment arm.
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
