Safety/Biomarker Study of CNTO 95 and Avastin in Solid Tumors

NCT00888043 | Completed Phase 1

• 1 other identifier: Pro00004929
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to find out what side effects the combination of the two study drugs, bevacizumab (Avastin) and CNTO 95 have on the body and to determine the highest dose of CNTO 95 that can be given with bevacizumab that is safe and well tolerated.

Conditions

Solid Tumors

Keywords

solid tumors; avastin; Phase I; combination therapy; bevacizumab

Outcome Measures

Primary Outcomes (2)

• To define a recommended phase II dose for the combination of CNTO 95 plus bevacizumab in subjects with advanced solid tumors.

  Every cycle (21 days)

• To evaluate dose limiting as well as non-dose limiting toxicities of this combination.

  Every cycle (21 days)

Secondary Outcomes (1)

• To explore the effect of the combination versus each agent individually on dermal wound angiogenesis in a skin biopsy, the clinical activity of this combination, and the association between blood- and urine-based biomarkers and clinical outcome.

  Every cycle (21 days)

Study Arms (1)

I

OTHER

CNTO 95 and avastin

Drug: CNTO 95 and avastin

Interventions

CNTO 95 and avastin DRUG

STAGE 1 (Dose escalation) Cohort # subjects CNTO 95 Bevacizumab * 2 3-6 2.5 mg/kg IV Q3 weeks 7.5 mg/kg IV Q3 weeks * 1 3-6 2.5 mg/kg IV Q3 weeks 15 mg/kg IV Q3 weeks 1. 3-6 5 mg/kg IV Q3weeks 15 mg/kg IV Q3 weeks 2. 3-6 10 mg/kg IV Q3 weeks 15 mg/kg IV Q3 weeks STAGE 2 (Biomarker) Cohort # subjects CNTO 95 Bevacizumab 3. 20 Recommended Phase II Dose Recommended Phase II Dose

Also known as: bevacizumab

I

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of advanced solid tumor refractory to standard therapy or for whom there is no standard therapy. Disease must be measurable by RECIST criteria.
• Age ≥ 18 years.
• Karnofsky performance status ≥ 70%.
• Life expectancy of at least 3 months.
• Patients must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/μl Platelets ≥ 100,000/μl Total bilirubin ≤ 1.5 X upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤ 2.5 X ULN, ≤ 5 X ULN if known hepatic metastases Creatinine clearance ≥ 50 mL/min/m2 for patients with creatinine levels (by Cockroft-Gault equation or 24 hour urine) Hemoglobin \> 9 g/dL Continuation of erythropoietin products is permitted. Hemoglobin must be stable above 9 g/dL for at least 2 weeks without blood transfusion to maintain hemoglobin level.
• Calcium (corrected for albumin) \> 8.7 mg/dL
• The effect of the investigational drugs on the developing human fetus is not known, but these drugs are likely to be embryo- and feto- toxic. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician and study PI immediately. Subjects who are pregnant and/or lactating are excluded from this study.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Subjects who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of study treatment. Subjects must not have had major surgery within the 28 days prior to study treatment day 1 or minor surgical procedures within the 7 days prior to study treatment day 1.
• Subjects who have received any other investigational agents within the 28 days prior to day 1 of the study.
• Subjects with known CNS metastases, centrally located non-small cell lung cancer (regardless of histologic sub-type), non-small cell lung cancer of squamous histology, and/or history of hemoptysis (\> ½ tsp BRB).
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg). Initiation of antihypertensive is permitted provided adequate control is documented 3 times over at least 1 week before starting treatment.
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Evidence of bleeding diathesis or coagulopathy. Subjects on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of study treatment (56 days for hepatectomy, open thoracotomy, major neurosurgery) or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure excluding study-related procedures or placement of a vascular access device, within 7 days prior to expected start of treatment.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
• Serious, non-healing wound, ulcer, or bone fracture
• Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC) ratio ≥ 1.0 or 24hr collection \>1g/24hr at screening
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to day 1 of study treatment
• History of stroke or transient ischemic attack within 6 months prior to day 1 of study treatment

Sponsors & Collaborators

• Herbert Hurwitz, MD: lead
• Centocor, Inc.: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Interventions

intetumumab; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Herbert I Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 23, 2009
• First Posted: April 24, 2009
• Study Start: March 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: January 1, 2015
• Last Updated: March 11, 2015

Record last verified: 2015-03

Locations

US (1)