Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colorectal Cancer

• Sponsor: University of Miami (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00449163
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arm: 1
• Actual Duration (Months): 48
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan, floxuridine, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Biological: Bevacizumab; Drug: Floxuridine; Drug: Irinotecan; Drug: Leucovorin	Phase 2

Detailed Description

For the purpose of this study treatment cycle consist of six weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29 according to the schedule. There will be no treatment delivered on weeks 3 & 6 (Days 15 and 36).

Disease will be evaluated by CT scan at the completion of every two cycles. Patients with complete response (CR), or partial response (PR), will be evaluated for possible surgical resection. Patients who become operable will continue to be evaluated for survival and disease relapse. Patients with stable disease (SD), and those with less than pCR after surgery should continue chemotherapy until radiographic evidence of tumor progression is identified or unacceptable side effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Avastin, Irinotecan, High Dose 24 Hour Continuous Intravenous Infusion of Floxuridine and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer
• Actual Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Combination Chemotherapy and Bevacizumab Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.

Biological: Bevacizumab; Other Names: Avastin ; Drug: Floxuridine; Other Names: 5-fluorodeoxyuridine ; Drug: Irinotecan; Other Names: Irinotecan Hydrochloride Camptosar ; Drug: Leucovorin; Other Names: Leucovorin calcium

Outcome Measures

Primary Outcome Measures

1. Overall Survival up to 2 Years [2 years]

   Percentage of patients with overall survival times of up to 2 years

Secondary Outcome Measures

1. Response Rate (Complete Response and Partial Response) [2 years]

   Percentage of patients achieving complete response or partial response per RECIST criteria ver 1.0

2. Median Progression-free Survival in Months [2 years]

   Median number of months subjects achieved progression-free survival

3. Rate of Toxicity in Study Participants [2 years]

   Evaluation the safety and toxicities of protocol regimen as evidenced by the rate of serious adverse events in study participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients must have stage IV, histologically confirmed diagnosis of Adenocarcinoma of the colon.

2. Patients must have bi-dimensionally measurable disease since the purpose of this study is to determine efficacy of treatment.

3. Patients must be previously untreated.

4. Patients must be over the age of 18 years.

5. Patients may not be pregnant. Patients of childbearing years must be using contraception.

6. Patients must have ECOG performance status of 0-1 or KPS of at least 70.

7. Patients must have life expectancy of ≥ two months.

8. Patients must have a white blood cell count of ≥1000/mm³ ANC > 1.0, platelets > 100,000/mm³.

9. Patients must have adequate renal function as documented by a serum creatinine of ≤ 1.5 mg/dl.

10. Patients must have a bilirubin of ≤ 1.5 mg/dl and an SGOT of ≤ three times normal for patients with no liver disease, and ≤ five times normal for those with liver metastases.

11. Patients must be informed of the investigational nature of the study and give written informed consent.

12. Patients must have indwelling central venous catheter or good peripheral intravenous catheter, preferably a port-a-cath.

13. Patients may have had prior surgery for their colorectal cancer. Patients must be at least 8 weeks beyond surgery and recovered from all effects of surgery.

14. Patients enrolled in this study may have a history of prior malignancy (5 years ago) provided that the patient is currently disease-free.

Exclusion Criteria:

1. Patients who have had prior chemotherapy or radiation therapy for their colorectal cancer, with exception of adjuvant chemo/radiation therapy.

2. Patients receiving concomitant radiation, hormonal therapy, chemotherapy, or immunotherapy.

3. Patients receiving any investigational drug within 30 days prior to start of this study.

4. Patients with serious underlying medical illnesses (including Congestive Heart Failure New York Heart Association Functional Classification 2-4) or active infection.

5. Patients with central nervous system metastasis must have completed radiation prior to entry into this protocol.

6. Patients with psychiatric conditions or associated conditions which would make participating in this study dangerous to their health.

7. Patients with uncontrolled hypertension.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami

Investigators

• Principal Investigator: Bach Ardalan, MD, University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Miami
• ClinicalTrials.gov Identifier: NCT00449163
• Other Study ID Numbers: 20060042; SCCC-2005145; WIRB-20060252
• First Posted: Mar 19, 2007
• Last Update Posted: May 11, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by University of Miami: stage IV colon cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum
• Additional relevant MeSH terms: Colorectal Neoplasms; Leucovorin; Bevacizumab; Irinotecan; Floxuridine; Levoleucovorin

Study Results

Participant Flow

Pre-assignment Detail	A total of 25 subjects were enrolled however; data were analyzed for only 22 of the subjects enrolled.

Arm/Group Title	Combination Chemotherapy and Bevacizumab
Arm/Group Description	Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.
Period Title: Overall Study
STARTED	25
COMPLETED	22
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Combination Chemotherapy and Bevacizumab
Arm/Group Description	Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.
Overall Participants	22
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 72.7%
>=65 years	6 27.3%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	11 50%
Male	11 50%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival up to 2 Years
Description	Percentage of patients with overall survival times of up to 2 years
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Chemotherapy and Bevacizumab
Arm/Group Description	Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.
Measure Participants	22
Number (95% Confidence Interval) [percentage of participants]	61 277.3%

2. Secondary Outcome

Title	Response Rate (Complete Response and Partial Response)
Description	Percentage of patients achieving complete response or partial response per RECIST criteria ver 1.0
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Chemotherapy and Bevacizumab
Arm/Group Description	Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.
Measure Participants	21
Number (95% Confidence Interval) [percentage of participants]	67 304.5%

3. Secondary Outcome

Title	Median Progression-free Survival in Months
Description	Median number of months subjects achieved progression-free survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Chemotherapy and Bevacizumab
Arm/Group Description	Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.
Measure Participants	21
Median (95% Confidence Interval) [months]	13

4. Secondary Outcome

Title	Rate of Toxicity in Study Participants
Description	Evaluation the safety and toxicities of protocol regimen as evidenced by the rate of serious adverse events in study participants.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combination Chemotherapy and Bevacizumab
Arm/Group Description	Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.
Measure Participants	22
Number [percentage of participants]	50 227.3%

Adverse Events

Adverse Event Reporting Description	Only serious adverse events (Grade 3 and 4) reported.
Arm/Group Title	Combination Chemotherapy and Bevacizumab
Arm/Group Description	Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.
All Cause Mortality
	Combination Chemotherapy and Bevacizumab
	Affected / at Risk (%)	# Events
Total	5/22 (22.7%)
Serious Adverse Events
	Combination Chemotherapy and Bevacizumab
	Affected / at Risk (%)	# Events
Total	11/22 (50%)
Gastrointestinal disorders
Diarrhea	3/22 (13.6%)
Small Bowel Obstruction	2/22 (9.1%)
General disorders
Fatigue	2/22 (9.1%)
Infections and infestations
Infection	1/22 (4.5%)
Injury, poisoning and procedural complications
Wound Dehiscence	1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolus	1/22 (4.5%)
Surgical and medical procedures
Port Site Thrombosis	2/22 (9.1%)
Vascular disorders
DVT	3/22 (13.6%)
Other (Not Including Serious) Adverse Events
	Combination Chemotherapy and Bevacizumab
	Affected / at Risk (%)	# Events
Total	0/22 (0%)

Limitations/Caveats

A total of 25 subjects were enrolled however; data were analyzed for 22 subjects only. Study was terminated early by the University of Miami Institutional Review Board.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.