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Advanced Malignant NeoplasmPhase 1NCT01552434

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 1 study testing Bevacizumab, Cetuximab and Laboratory Biomarker Analysis in people with Advanced Malignant Neoplasm and Castleman Disease, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
Bevacizumab, Cetuximab and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
154 participants
Where
1 siteUnited States
Study dates
16 Oct 2012to 8 May 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I Trial of Bevacizumab, Temsirolimus Alone and in Combination With Valproic Acid, or Cetuximab in Patients With Advanced Malignancy and Other Indications

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
Bevacizumab, Cetuximab, Laboratory Biomarker Analysis, Pharmacological Study, Temsirolimus
Keywords
Temsirolimus, CCI-779, Torisel, Bevacizumab, Avastin, rhuMAb-VEGF, Anti-VEGF Monoclonal Antibody, Advanced Cancers, Advanced Malignancy, Metastatic, cancer, Cetuximab, C225, Erbitux, IMC-C225, Valproic Acid
Medical subject headings
Castleman Disease, Erdheim-Chester Disease, Mouth Neoplasms, Lymphangioleiomyomatosis, Endocrine Gland Neoplasms, Neoplasms, Urologic Neoplasms, Neoplasms, Mesothelial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • CetuximabBiological

    Also called Cetuximab Biosimilar CMAB009, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225

    Given IV

  • Laboratory Biomarker AnalysisOther

    Optional correlative studies

  • Pharmacological StudyOther

    Optional correlative studies

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

  • Valproic AcidDrug

    Also called Depakene, Stavzor, Valproate

    Given PO

Study groups in NCT01552434
Study groupRoleWhat they receive
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.
Receives: Biological: Bevacizumab; Biological: Cetuximab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus
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.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus; Drug: Valproic Acid
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.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 4 weeks

  2. 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.

    Measured: 4 weeks

Secondary outcomes (2)

  1. Anti-tumor efficacy of each combination (objective response)

    Will be determined by Response Evaluation Criteria In Solid Tumors and World Health Organization criteria

    Measured: Up to 6 years

  2. Levels of surrogate anti-angiogenesis markers

    Correlated with anti-tumor activity.

    Measured: Up to week 4 of course 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2012 (estimated)
  2. Study start16 Oct 2012
  3. Primary completion8 May 2026
  4. Study completion8 May 2026

Why it stopped: \< 75 % participation

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
154 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01552434
Sponsor's protocol ID
2012-0061
Other IDs
NCI-2012-00347, 2012-0061
Status last verified
May 2026
First submitted
7 Mar 2012
Last updated
15 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 41389341

  • Nelson 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.

    PubMed 37311055

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab, Cetuximab and Laboratory Biomarker Analysis in people with Advanced Malignant Neoplasm and Castleman Disease, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: \< 75 % participation). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01552434, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.

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