Bendamustine and Bevacizumab for Advanced Cancers

A Phase I Study of Bendamustine and Bevacizumab for Patients With Advanced Cancers

The goal of this clinical research study is to find the highest tolerable combination dose of bendamustine and bevacizumab that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Bendamustine; Drug: Bevacizumab

Detailed Description

The Study Drugs:

Bendamustine is designed to damage DNA (the genetic material) of cancer cells. Bendamustine also interferes with the creation of new DNA, which may keep cancer cells from repairing themselves or forming new cancer cells.

Bevacizumab is designed to block the growth of blood vessels that supply the nutrients needed for tumor growth, which may prevent or slow down the growth of cancer cells. Bevacizumab is no longer FDA approved to treat breast cancer.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of bendamustine based on when you join this study. Up to 4 dose levels of bendamustine will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of bendamustine is found.

All participants will receive the same dose level of bevacizumab.

Study Drug Administration:

You will receive bendamustine by vein over 30-60 minutes on Days 1 and 2 of each 28-day study cycle.

You will receive bevacizumab by vein on Days 1 and 15 of each cycle. The first time you receive bevacizumab, it will be given over 90 minutes. If you tolerate it well, the rest of the doses will be given over 30-60 minutes.

Study Visits:

On Day 1 of each cycle:

• You will have a physical exam, including measurement of your weight and vital signs.
• Blood (about 1 tablespoon ) will be drawn for routine tests.
• Women who are able to become pregnant will have a urine pregnancy test.

Every 2 cycles (Cycles 2, 4, 6, and so on):

• Blood (about 1 tablespoon) will be drawn to test for tumor markers.
• A chest x-ray, CT scan, MRI scan, PET scan, and/or PET/CT scan will be performed to check the status of the disease. These scans will also be performed at any time that the doctor thinks it is needed to check the status of the disease. If the study doctor thinks it is in your best interest, other types of scans that have not been listed here may also be performed.

Length of Study:

You may continue taking the study drug combination for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse or intolerable side effects occur.

Follow-Up Visit:

Six (6) weeks after you stop taking the study drug combination for any reason, the following tests and procedures will be performed:

• You will have a physical exam.
• Your performance status will be recorded.
• Blood (about 2 teaspoons) will be drawn for routine tests.
• If the study doctor thinks it is needed, a chest x-ray, CT scan, MRI scan, PET scan and/or PET/CT scan will be performed to check the status of the disease. If the study doctor thinks it is in your best interest, other types of scans that have not been listed here may also be performed.

This is an investigational study. Bendamustine is FDA approved and commercially available for the treatment of chronic lymphoid leukemia and non-Hodgkin's lymphoma. Bevacizumab is FDA approved and commercially available for the treatment of metastatic colorectal cancer, non-small-cell lung cancer (NSCLC), and a type of brain cancer called glioblastoma multiforme. The use of these drugs in combination in advanced cancer is investigational.

Up to 55 participants will take part in this study. All will be enrolled at M. D. Anderson.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • UT MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have histologically confirmed cancer.
2. Patients should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that increases survival by at least 3 months.
3. Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 (capable of all self care but unable to carry out any work activities). Pediatric: performance status Karnovsky (>10) or Lansky (<10).
4. Adequate renal function (serum creatinine </= 2.0 mg/dL or the calculated Glomerular Filtration Rate (GFR) >/= 40 mL/min if creatinine > 2.0 mg/dL). Pediatric: serum creatinine </= 1.5 mg/dL or 2x upper limit of normal, for age.
5. Hepatic function: total bilirubin </= 1.0 mg/dL (Patients with Gilbert's Syndrome must have a total bilirubin </= 3.0 mg/dL); ALT </= 3 times upper limit of normal. If patient has liver metastases, total bilirubin </= 5 mg/dL; ALT </= 5 times upper limit of normal.
6. Adequate bone marrow function (Absolute neutrophil count (ANC) >/= 1,000 cells/uL; Platelets (PLT) >/= 75,000 cells/uL), unless these abnormalities are due to bone marrow involvement.
7. At least three weeks from previous cytotoxic chemotherapy. After targeted or biologic therapy there should be 5 half-lives or 3 weeks, whichever is shorter.
8. All females in childbearing age MUST have a negative urine human chorionic gonadotropin (HCG) test unless prior hysterectomy or menopause (defined as age above 55 and six months without menstrual activity). Patients should not become pregnant or breast-feed while on this study. Sexually active patients should use effective birth control.
9. Must be >/= 13 years of age.
10. Sign informed consent. Pediatric participants: age 13-17 would sign assent, parent or guardian would sign consent.

Exclusion Criteria:

1. Pregnant females.
2. Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements.
3. Serious or non-healing wound, ulcer or bone fracture.
4. Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg).
5. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection requiring parental antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements.
6. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days.
7. Patients with clinical bleeding, active gastric or duodenal ulcer.
8. Patients with history of bleeding central nervous system (CNS) metastasis will be excluded from the trial.
9. Patients with major surgery within 28 days prior to entering the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bendamustine + Bevacizumab; Bendamustine starting dose of 70 mg/m^2 by vein on Days 1 and 2 of a 28 day cycle. Bevacizumab 10 mg/kg by vein on Days 1 & 15 of every 28 day cycle.	Drug: Bendamustine; Starting dose of 70 mg/m^2 by vein on Days 1 and 2 of a 28 day cycle; Other Names: Treanda; CEP-18083; SDX-105; Bendamustine hydrochloride; Bendamustine HCI; Drug: Bevacizumab; 10 mg/kg by vein on Days 1 & 15 of every 28 day cycle; Other Names: Avastin; Anti-VEGF monoclonal antibody; rhuMAb-VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD) of Bendamustine and Bevacizumab	MTD defined as highest dose below any dose that has one third or more patients with dose limiting toxicity (DLT). If not more than 33% of the patients in the cohort develop DLT, this cohort considered MTD. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in most current version of NCI Common Toxicity Criteria for Adverse Effects (CTCAE).	28 days

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Comprehensive Cancer Network; Cephalon

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: June 25, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (Estimate): June 29, 2010

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: November 16, 2015
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Bevacizumab; Bendamustine
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bendamustine Hydrochloride; Bevacizumab
• Other Study ID Numbers: 2009-0979; NCI-2010-01690 (Registry Identifier: NCI CTRP)