Bevacizumab, Chemotherapy and Valproic Acid in Advanced Sarcomas

NCT01106872 | Completed Phase 1 DMC

• 2 other identifiers: 200911736AVF4761s
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the combination of the chemotherapy drugs Gemcitabine, bevacizumab, and docetaxel with valproic acid to treat patients with metastatic sarcoma. Valproic acid is used by people who have seizures to prevent seizures from happening; however, its use in cancer is investigational. This study will help define the proper dosing of this valproic acid. We will assess the safety of valproic acid with the combination of the above chemotherapy drugs and check for possible side effects. Valproic acid may improve the function of the chemotherapy drugs against the cancer.

Conditions

Sarcoma; Soft Tissue Sarcoma; Locally Advanced Sarcoma; Unresectable Sarcoma; Metastatic Sarcoma

Keywords

Sarcoma; Soft Tissue Sarcoma; Locally Advanced Sarcoma; Unresectable Sarcoma; Metastatic Sarcoma; Valproic Acid; Bevacizumab; Histone Deacetylase Inhibitor

Outcome Measures

Primary Outcomes (1)

• Evaluate toxicities

  Dose-limiting toxicities per CTCAE 4.0; grade 4 hematologic toxicity; grade 3 or 4 hepatotoxicity.

  After one cycle (3 weeks)

Study Arms (1)

Treatment

EXPERIMENTAL

Bevacizumab Combined with Gemcitabine, Docetaxel and Valproic Acid in Advanced Sarcoma

Drug: Bevacizumab, Gemcitabine, Docetaxel and Valproic Acid

Interventions

Bevacizumab, Gemcitabine, Docetaxel and Valproic Acid DRUG

Also known as: Avastin, Gemzar, Taxotere, Depakene, Stavzor

Treatment

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 18 years old.
• ECOG Performance Status of ≤ 2.
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed.
• Patients must meet the following laboratory criteria:
• Hematology: Neutrophil count of \> 1500/mm3; Platelet count of \>100,000/mm3L; Hemoglobin ≥ 9 g/dL Biochemistry:AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement; Serum bilirubin ≤ 1.5 x ULN; Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min; Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN; Serum potassium ≥ LLN; Serum sodium ≥ LLN; Serum albumin ≥ LLN or 3g/dl; Patients with any elevated alkaline phosphatase due to bone metastasis can be enrolled
• Screening EKG with a QTc less than 450 msec confirmed by central laboratory prior to enrollment to the study.
• Baseline MUGA or ECHO done only in subjects with prior doxorubicin exposure. The test must demonstrate LVEF ≥ the lower limit of the institutional normal.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment and must be willing to use two methods of contraception one of them being a barrier method during the study and for 3 months after last study drug administration
• Any patient with the diagnosis of locally advanced, unresectable or metastatic sarcoma from any site. These include untreated patients or those treated with chemotherapy 1st line, 2nd line and 3rd line. Patients must have measurable disease defined as at least 1 lesion ≥ 1cm in the greatest dimension.
• Previous exposure to Gemcitabine and Taxotere will only be allowed if there is no residual toxicity from previous treatments. Toxicity must be graded as 0 or 1 prior to study.
• Patients must have had disease progression on or following their most recent treatment regimen or on presentation for the first time with locally advanced unresectable or metastatic disease.
• All subtypes of sarcoma are eligible for the trial.

You may not qualify if:

• Prior use of Bevacizumab for the treatment of cancer.
• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer.
• Patients who will need valproic acid for any medical condition .
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \> 100 mmHg).
• Prior history of hypertensive crisis or hypertensive encephalopathy.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction or unstable angina within 6 months prior to Day 1.
• History of stroke or transient ischemic attack within 6 months prior to Day 1.
• Known CNS disease, except for treated brain metastasis: Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
• History of hemoptysis (\>/= 1/2 teaspoon of bright red blood per episode) wit hin 1 month prior to Day 1
• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
• Serious, non-healing wound, active ulcer, or untreated bone fracture

Sponsors & Collaborators

• Mohammed M Milhem: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Bevacizumab; Gemcitabine; Docetaxel; Valproic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Mohammed Milhem, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: March 22, 2010
• First Posted: April 20, 2010
• Study Start: September 1, 2010
• Primary Completion: July 1, 2017
• Study Completion: August 22, 2017
• Last Updated: August 10, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)