Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease
A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid, or Cetuximab in Patients With Advanced Malignancy and Other Indications
2 other identifiers
interventional
155
1 country
1
Brief Summary
This phase I trial studies the side effects and best dose of bevacizumab and temsirolimus alone or in combination with valproic acid or cetuximab in treating patients with a malignancy that has spread to other places in the body or other disease that is not cancerous. Immunotherapy with bevacizumab and cetuximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as valproic acid, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether bevacizumab and temsirolimus work better when given alone or with valproic acid or cetuximab in treating patients with a malignancy or other disease that is not cancerous.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2012
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 7, 2012
CompletedFirst Posted
Study publicly available on registry
March 13, 2012
CompletedStudy Start
First participant enrolled
October 16, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2026
April 24, 2026
October 1, 2025
14 years
March 7, 2012
April 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (MTD) of bevacizumab, defined as the dose level below the dose at which 2 of 6 patients experience drug-related dose limiting toxicity (DLT)
Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
4 weeks
MTD of temsirolimus, defined as the dose level below the dose at which 2 of 6 patients experience DLT
Graded by the NCI CTCAE version 3.0.
4 weeks
Secondary Outcomes (2)
Anti-tumor efficacy of each combination (objective response)
Up to 6 years
Levels of surrogate anti-angiogenesis markers
Up to week 4 of course 1
Other Outcomes (1)
The properties of the tissue microvasculature.
Up to week 4 of course 1
Study Arms (3)
Group I (temsirolimus, bevacizumab, cetuximab)
EXPERIMENTALPatients receive temsirolimus 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 60-120 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II (temsirolimus, bevacizumab, valproic acid)
EXPERIMENTALPatients receive temsirolimus and bevacizumab as in Group I and valproic acid PO on days 1-7 and 15-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group III (temsirolimus, bevacizumab)
EXPERIMENTALPatients receive temsirolimus and bevacizumab as in Group I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Optional correlative studies
Optional correlative studies
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
Piha-Paul SA, Tseng C, Thompson E, Stafford RJ, Le H, Kang L, Fu S, Tsimberidou A, Blumenschein G, Ahnert JR, Slopis JM, Hong D, Naing A, Meric-Bernstam F, Ng CS, Westin S, Sood AK. Phase I study of bevacizumab and temsirolimus combination therapy in advanced malignancies: safety, efficacy, and ovarian cancer expansion. Oncologist. 2026 Feb 5;31(3):oyaf413. doi: 10.1093/oncolo/oyaf413.
PMID: 41389341DERIVEDNelson BE, Tsimberidou AM, Fu X, Fu S, Subbiah V, Sood AK, Rodon J, Karp DD, Blumenschein G, Kopetz S, Pant S, Piha-Paul SA. A Phase I Trial of Bevacizumab and Temsirolimus in Combination With Valproic Acid in Advanced Solid Tumors. Oncologist. 2023 Dec 11;28(12):1100-e1292. doi: 10.1093/oncolo/oyad158.
PMID: 37311055DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sarina A Piha-Paul
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 7, 2012
First Posted
March 13, 2012
Study Start
October 16, 2012
Primary Completion (Estimated)
October 31, 2026
Study Completion (Estimated)
October 31, 2026
Last Updated
April 24, 2026
Record last verified: 2025-10