Expanded Cohort for Metastatic Colorectal Cancer (MCRC) Using Bevacizumab + Everolimus

NCT00597506 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00001574
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find the safest and most effective dose of the drugs bevacizumab and everolimus given in combination for the treatment of metastatic colorectal cancer. Bevacizumab (also called Avastin™) is a drug that is given intravenously (through a vein). Everolimus (also called RAD001) is a tablet that is taken by mouth. Bevacizumab is a protein that is thought to prevent the formation of blood vessels tumors need to grow. RAD001 has multiple capabilities, like bevacizumab it may prevent the formation of blood vessels needed by tumors and it also may stop tumor growth. This study will try to find the safest dose of these drugs that can be tolerated when taken in combination. The study will look at how the drugs work in the body, and will see if there is any effect on metastatic colorectal cancer.

Conditions

Colorectal Adenocarcinoma

Keywords

colorectal; refractory; adenocarcinoma; bevacizumab; everolimus

Outcome Measures

Primary Outcomes (2)

• Overall Response

  Overall response is composed of complete responses and partial responses. Complete response (CR): disappearance of all target lesions; Partial response: at least a 30 percent decrease in the sum of the longest diameter of the target lesions taking as reference the baseline sum longest diameter. Response is assessed at each subject's restaging, approximately ever 2 months.

  Measured 1 month after the last treated subject came off treatment

• Progression Free Survival (PFS)

  8 week PFS

  interval between start of treatment and 8-week

Study Arms (1)

Bevacizumab and Everolimus

EXPERIMENTAL

10 mg Everolimus(RAD001) daily by mouth, days 1-28 10 mg/kg intravenous bevacizumab given days 1 and 15 of each cycle

Drug: Bevacizumab; Drug: Everolimus

Interventions

Bevacizumab DRUG

10 mg/kg intravenous bevacizumab given days 1 and 15 of each cycle

Also known as: Avastin

Bevacizumab and Everolimus

Everolimus DRUG

10 mg Everolimus(RAD001) daily by mouth, days 1-28

Also known as: RAD001

Bevacizumab and Everolimus

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed adenocarcinoma of the colon or rectum that has progressed on, or patient could not tolerate, fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab and/or panitumumab chemotherapy. Disease must be measurable or evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1. Patients must not have had major surgery within the 28 days prior to study day 1 or minor surgical procedures within the 7 days prior to study day 1.
• Age \>18 years.
• Karnofsky performance status \> 70 percent
• Life expectancy of at least 3 months.
• Patients must have normal organ and marrow function as defined in the protocol
• 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; abstinence) 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. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Patients 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:

• Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of the study.
• Patients who have received any other investigational agents within the 28 days prior to day 1 of the study.
• Patients with known central nervous system (CNS) metastases.
• 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 over at least 1 week before starting treatment.
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy. Patients 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 study enrollment (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 greater than or equal to 1.0 at screening
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix G)
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment

Sponsors & Collaborators

• Herbert Hurwitz: lead
• Novartis Pharmaceuticals: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Bevacizumab; Everolimus

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; 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; Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Herbert Hurwitz, MD
• Organization: Duke University Medical Center

herbert.hurwitz@duke.edu

919-668-1861

Study Officials

• Herbert I Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 18, 2008
• Study Start: October 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: December 27, 2012
• Results First Posted: August 16, 2012

Record last verified: 2012-12

Locations

US (1)