Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT01552434
• Date of registration: 07/03/2012
• Prospective Registration: Yes
• Primary sponsor: M.D. Anderson Cancer Center
• Public title: Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease
• Scientific 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
• Date of first enrolment: March 16, 2012
• Target sample size: 155
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01552434
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Sarina A Piha-Paul
• Affiliation: M.D. Anderson Cancer Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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



Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Recurrent Male Reproductive System Carcinoma

Lip and Oral Cavity Carcinoma

Malignant Endocrine Neoplasm

Malignant Male Reproductive System Neoplasm

Metastatic Urothelial Carcinoma

Recurrent Female Reproductive System Carcinoma

Stage IIIA Breast Cancer AJCC v7

Advanced Malignant Neoplasm

Recurrent Adult Soft Tissue Sarcoma

Stage IV Pharyngeal Cancer

Stage IVA Pharyngeal Cancer

Recurrent Malignant Neoplasm

Recurrent Pharyngeal Carcinoma

Stage III Pharyngeal Cancer

Stage IVC Pharyngeal Cancer

Malignant Respiratory Tract Neoplasm

Metastatic Malignant Neoplasm

Recurrent Thyroid Gland Carcinoma

Stage IIIB Breast Cancer AJCC v7

Neurofibromatosis Type 2

Recurrent Childhood Soft Tissue Sarcoma

Castleman Disease

Malignant Neoplasm

Malignant Urinary System Neoplasm

Recurrent Breast Carcinoma

Refractory Malignant Neoplasm

Stage IIIC Breast Cancer AJCC v7

Stage IV Breast Cancer AJCC v6 and v7

Malignant Thoracic Neoplasm

Soft Tissue Neoplasm

Digestive System Carcinoma

Erdheim-Chester Disease

Lymphangioleiomyomatosis

Malignant Female Reproductive System Neoplasm

Mesothelial Neoplasm

Recurrent Digestive System Carcinoma

Stage III Breast Cancer AJCC v7

Thyroid Gland Neoplasm

Stage IVB Pharyngeal Cancer

Intervention(s)

Other: Pharmacological Study

Other: Laboratory Biomarker Analysis

Drug: Temsirolimus

Drug: Valproic Acid

Biological: Bevacizumab

Biological: Cetuximab

Primary Outcome(s)

MTD of temsirolimus, defined as the dose level below the dose at which 2 of 6 patients experience DLT [Time Frame: 4 weeks]

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]

Secondary Outcome(s)

Anti-tumor efficacy of each combination (objective response) [Time Frame: Up to 6 years]

Levels of surrogate anti-angiogenesis markers [Time Frame: Up to week 4 of course 1]

Secondary ID(s)

NCI-2012-00347

2012-0061

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)