Bevacizumab and Temsirolimus Alone or in Combination with Valproic Acid or Cetuximab in Treating Patients with Advanced or Metastatic Malignancy or Other Benign Disease
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a complete response of at least 10% or improves survival by at least three months; in addition, patients with disease that are “benign” by pathology, but relentlessly progressive, leading to disability, pain, and premature death in the majority of cases (including, but not limited to lymphangioleiomyomatosis [LAM], type 2 neurofibromatosis [NF], Erdheim Chester disease, and Castleman’s disease) may also be considered for enrollment
- Patients should be at least four weeks from the last day of therapeutic radiation or cytotoxic chemotherapy or from antibody therapy, or at least five half-lives from non-cytotoxic targeted or biologic therapy; patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Karnofsky >= 60%
- Lansky performance status of >= 60% for participants 16 years old or younger
- Absolute neutrophil count >= 1,000/mL
- Platelets >= 50,000/mL
- Creatinine =< 3 X upper limit of normal (ULN)
- Total bilirubin =< 3.0
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X ULN
- Fasting level of total cholesterol of no more than 350 mg/dL
- Triglyceride level of no more than 400 mg/dL
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after the last dose
- Ability to understand and the willingness to sign a written informed consent document
- Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
- Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication)
- Patients with clinically significant cardiovascular disease: History of CVA (cerebrovascular accident) within 6 months, myocardial infarction or unstable angina within 6 months, unstable angina pectoris
- Pregnant or breast-feeding women
- History of hypersensitivity to bevacizumab, murine products, or any component of the formulation
- History of hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any component of the formulation
- History of hypersensitivity to cetuximab, murine products, or any component of the formulation
- Patients that are taking cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducers and/or inhibitors; if a patient has a history of taking CYP3A4 inducers and/or inhibitors prior to enrollment on the protocol, it is strongly recommended that the patient stops the drug and waits at least 5 half-lives of said drug before initiating therapy on protocol
- Colorectal cancer patients with known v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (for the arm combining bevacizumab, temsirolimus and cetuximab)
- Patients who have had major surgery within 6 weeks of enrollment in the study
I. To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of treatment with bevacizumab and temsirolimus in combination and plus valproic acid or cetuximab.
I. Preliminary descriptive assessment of anti-tumor efficacy of each combination.
II. Preliminary assessment of the pharmacokinetic, pharmacodynamic markers of target inhibition and correlates of response (optional).
OUTLINE: This is a dose-escalation study of bevacizumab and temsirolimus. Patients are assigned to 1 of 3 treatment groups.
GROUP I: Patients receive temsirolimus intravenously (IV) over 30-60 minutes on days 1, 8, 15, and 22; bevacizumab IV over 30-90 minutes on days 1 and 15; and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22.
GROUP II: Patients receive temsirolimus and bevacizumab as in Group I and valproic acid orally (PO) daily on days 1-7 and 15-21.
GROUP III: Patients receive temsirolimus and bevacizumab as in Group I.
In all groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Trial Phase Phase I
Trial Type Treatment
M D Anderson Cancer Center
Sarina A. Piha-Paul
- Primary ID 2012-0061
- Secondary IDs NCI-2012-00347
- Clinicaltrials.gov ID NCT01552434