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Expanded Cohort of Patients With Refractory Metastatic Colorectal Cancer (MCRC) Treated With Bevacizumab and Everolimus

Phase 2
18 Years
Not Enrolling
Colorectal Adenocarcinoma

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Trial Information

Expanded Cohort of Patients With Refractory Metastatic Colorectal Cancer (MCRC) Treated With Bevacizumab and Everolimus

This open-label, non-randomized expanded cohort trial of bevacizumab and RAD001 for patients
with refractory metastatic colorectal cancer is designed to assess preliminary efficacy as
well as the safety and tolerability of this combination. Patients will be accrued to this
study at Duke University Medical Center and The Duke Oncology Outreach Network (DON)

After satisfying eligibility and screening criteria, patients will be treated on 28 day

- The treatment regimen is as follows:

10 mg/kg Bevacizumab intravenous on days 1 and 15 and 10mg everolimus (RAD001) daily by

- Toxicity will be assessed every visit, and as clinically indicated.

- Efficacy will be assessed every 2 cycles, and as clinically indicated.

- Patients may remain on treatment as long as they are deemed to be clinically benefiting
from treatment, do not have progressive disease on restaging imaging (Section 6.0), or
do not have any other reason for discontinuation of treatment as outlined in Section

- Patients will undergo correlative studies as outlined in the study protocol

Inclusion Criteria:

- 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)

- 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

Exclusion Criteria:

- 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

- 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

- 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

- History of stroke or transient ischemic attack within 6 months prior to study

- History of intolerance or hypersensitivity to prior treatment with bevacizumab or

- Chronic treatment with systemic steroids or another immunosuppressive agent, though
steroids may be used on an as-needed basis - ie - for treatment of nausea. Treatment
with megace or low dose glucocorticoids is permitted for treatment of anorexia.

- Other concurrent severe and/or uncontrolled medical disease which could compromise
safety of treatment as so judged by treating physician

- A known history of HIV seropositivity, hepatitis C virus, acute or chronic active
hepatitis B infection, or other serious chronic infection requiring ongoing

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter drug absorption (e.g., inflammatory bowel disease, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel

- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
(except coumadin). No history of active GI bleeding or other major bleeding within
previous 6 months.

- Patients unwilling to or unable to comply with the protocol

- Medical need for the continuous administration of any drugs which affect Cytochrome
P450, family 3, subfamily A (CYP3A), though the use of low dose glucocorticoids for
anorexia and /or nausea is permitted.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness/social situations that would limit safety or
compliance with study requirements or may interfere with the interpretation of the

- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any
evidence of interstitial lung disease on baseline chest CT scan.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Response

Outcome Description:

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.

Outcome Time Frame:

Measured 1 month after the last treated subject came off treatment

Safety Issue:


Principal Investigator

Herbert I Hurwitz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:




Start Date:

October 2007

Completion Date:

June 2010

Related Keywords:

  • Colorectal Adenocarcinoma
  • colorectal
  • refractory
  • adenocarcinoma
  • bevacizumab
  • everolimus
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colorectal Neoplasms



Duke University Medical Center Durham, North Carolina  27710