Neoadjuvant FOLFOX Plus Bevacizumab Chemotherapy in Patients With Locally Advanced Colon Cancer

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00826800
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 2
• Locations: 5
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to see if giving chemo-therapy for colon cancer before surgery can shrink the cancer and lead to a higher rate of cure than operating first and then giving chemotherapy. Standard treatment for colon cancer is to first operate, and then, if the tumor is advanced, give chemotherapy for about 6 months. However, surgery delays the time until chemotherapy can start, since the body needs time to heal from the operation. During this time any cancer cells that remain in the body that were not removed by the operation may be allowed to grow. Giving chemotherapy first could attack the cancer cells right from the start, not only at the tumor site that we know of, but also at the site of any cancer cells that may have spread to other parts of the body. Another possible reason why giving chemo therapy first might work better is that the blood vessels that feed the cancer cells are intact before surgery and thus chemotherapy can travel directly to the cancer.

This study will also use the drug bevacizumab, in addition to the standard chemotherapy. Bevacizumab has been on the market since 2004 for colon cancer that has spread to other organs, but its use in earlier stage colon cancer, as planned in this trial, is still under study.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer	Drug: FOLFOX and bevacizumab	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Neoadjuvant FOLFOX Plus Bevacizumab Chemotherapy in Patients With Locally Advanced Colon Cancer
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Neoadjuvant FOLFOX Plus Bevacizumab FOLFOX and bevacizumab will be given to colon cancer patients for 4 cycles over 8 weeks; an additional 2 cycles of FOLFOX without bevacizumab will be given for a total of 12 weeks of pre-operative chemotherapy.Restaging will be performed within 3 weeks of the 6th chemotherapy cycle. Colon surgery will be performed between weeks 3 and 6 subsequent to the 6th cycle of FOLFOX. Patients receiving preoperative chemotherapy without radiation will wait a minimum of 3 weeks from their last dose of chemotherapy, and 6 weeks from their last dose of bevacizumab, before proceeding to surgery. Specifically, it is intended that patients will undergo surgery between 3-6 weeks from completion of their neoadjuvant therapy as deemed clinically appropriate by their surgeon and medical oncologist. This permits a 7-10 week interval between the 4th bevacizumab administration and colon surgery.

Drug: FOLFOX and bevacizumab; The patient will receive six treatments, two weeks apart. On each treatment day you will get Oxaliplatin, 5-FU,Leucovorin. On the first four treatments you will also get Bevacizumab (Avastin). These drugs are given through a Mediport. They will be given in an outpatient chemotherapy unit. Each tx will take about 4 hours. A pump for the 5-FU is worn around your waist. This drug is given over 2 days. Part II: Colon Cancer Surgery is standard practice, and is not a research procedure.Part III: Post-operative Re-Evaluation and Recovery The doctor will decide on the type of chemotherapy based on how the patient responded to the first chemotherapy. The plan will be for the patient to get 6 more doses of FOLFOX, without any further bevacizumab, unless your doctor finds a reason to do otherwise.

Outcome Measures

Primary Outcome Measures

1. To Determine the Pathologic Complete Response (Path CR) Rate in Patients With Locally Advanced (Stage II or III) Colon Cancer to FOLFOX-bevacizumab Administered as Neoadjuvant. [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• NOTE: Patients may sign consent and be registered for this protocol prior to completion of assessment of criteria 6.1.1 and 6.1.2, (assuming all other eligibility criteria are met) so that endocolonic ultrasound and biopsy may be performed on study; as these procedures may be necessary to determine TNM staging and/or histopathology; however criteria 6.1.1 and 6.1.2 must be successfully met prior to patient receiving chemotherapy on this trial.

• 6.1.1 Clinical T1N1-2/T2N1-2/T3N0/T3N1-2/T4Ni-N2 adenocarcinomas of the colon determined by endocolonic ultrasound (ECUS) performed at MSKCC.

• 6.1.2 Colonoscopy with endoscopic biopsy of tumor at MSKCC for disease confirmation and correlative studies. Pathological confirmation of adenocarcinoma or poorly differentiated carcinoma as the primary histology.

• CT or MRI scans (done within 30 days of registration) of the Chest, Abdomen and Pelvis all without clear evidence of distant metastatic (M1) disease.

• Candidates for systemic therapy with FOLFOX and bevacizumab based on the opinion of the primary treating medical oncologist.

• Candidates for complete surgical resection prior to administration of any therapy.

• Performance status of ECOG 0 or 1.

• Patients must be of age ≥18 years.

• ANC ≥ 1.5 cells/mm3, PLT >150,000/mm3.

• Serum creatinine < or = to 1.5 OR creatinine clearance (measured or calculated) greater than 60 ml/min.

Exclusion Criteria:

• Primary tumor clearly unresectable.

• Tumors with neuroendocrine histology.

• Patients with tumors that require placement of an endocolonic stent prior to treatment initiation.

• Patients with a history of stroke or TIA.

• Patients with history of thrombotic episodes such as deep venous thrombosis, pulmonary embolus, MI, or CVA occurring more than 12 months prior to enrollment may be considered for protocol participation provided that they are on stable doses of anticoagulant therapy. Similarly, patients anticoagulated for atrial fibrillation or other conditions may participate provided that they are on stable dose of anticoagulant therapy. Clinicians must note the higher risk of bevacizumab therapy amongst patients with history of thromboembolic disorders and consideration for participation is at the discretion of the treating physician.

• No other experimental therapies (including chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental drugs) of any kind are permitted while the patient is receiving study treatment.

• Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 6 months after the study. Subjects who are men must also agree to use effective contraception.

• Note: Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 6 months after the study in such a manner that the risk of pregnancy is minimized.

• WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35mIU/mL]. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential.

• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

• Women who are pregnant or breast feeding. Note: women with a positive pregnancy test on enrollment or prior to study drug administration will be removed from study.

• Patients with any other concurrent medical or psychiatric condition or disease which, in the investigator's judgment, would make the patient inappropriate for entry into this study.

• Patients with a history in the past five years of a prior malignancy, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Inadequately controlled, persistent (on more than one occasion) hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg).

• Prior history of hypertensive crisis or hypertensive encephalopathy.

• New York Heart Association (NYHA) Grade II or greater congestive heart failure

• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1

• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1

• Serious, non-healing wound, active ulcer, or untreated bone fracture (adjuvant trials: bone fractures must be healed

• Proteinuria as demonstrated by a UPC ratio ≥ 1.0 at screening

• Known hypersensitivity to any component of bevacizumab

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan-Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
3	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
4	Memorial Sloan-Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York	United States	11570
5	Memoral Sloan Kettering Cancer Center@Phelps	Sleepy Hollow	New York	United States

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Genentech, Inc.

Investigators

• Principal Investigator: Leonard Saltz, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00826800
• Other Study ID Numbers: 08-162
• First Posted: Jan 22, 2009
• Last Update Posted: Apr 15, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Memorial Sloan Kettering Cancer Center: BEVACIZUMAB (AVASTIN); FLUOROURACIL; LEUCOVORIN; OXALIPLATIN; Chemotherapy
• Additional relevant MeSH terms: Colonic Neoplasms; Bevacizumab

Study Results

Participant Flow

Recruitment Details	Protocol Open to Accrual: 01/19/2009 Protocol Closed to Accrual: 04/13/2010 Primary Completion Date (if applicable): 12/28/2010 Recruitment Location is the medical clinic

Arm/Group Title	Neoadjuvant FOLFOX Plus Bevacizumab
Arm/Group Description	FOLFOX and bevacizumab: The patient will receive six treatments, two weeks apart. On each treatment day patient will get Oxaliplatin, 5-FU,Leucovorin. On the first four treatments, patient will also get Bevacizumab (Avastin).
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Neoadjuvant FOLFOX Plus Bevacizumab
Arm/Group Description	FOLFOX and bevacizumab: The patient will receive six treatments, two weeks apart. On each treatment day patient will get Oxaliplatin, 5-FU,Leucovorin. On the first four treatments, patient will also get Bevacizumab (Avastin).
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 50%
>=65 years	1 50%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	To Determine the Pathologic Complete Response (Path CR) Rate in Patients With Locally Advanced (Stage II or III) Colon Cancer to FOLFOX-bevacizumab Administered as Neoadjuvant.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neoadjuvant FOLFOX Plus Bevacizumab
Arm/Group Description	FOLFOX and bevacizumab: The patient will receive six treatments, two weeks apart. On each treatment day patient will get Oxaliplatin, 5-FU,Leucovorin. On the first four treatments, patient will also get Bevacizumab (Avastin).
Measure Participants	2
Complete Response	1 50%
Partial Response	1 50%

Adverse Events

Arm/Group Title	Neoadjuvant FOLFOX Plus Bevacizumab
Arm/Group Description	FOLFOX and bevacizumab: The patient will receive six treatments, two weeks apart. On each treatment day patient will get Oxaliplatin, 5-FU,Leucovorin. On the first four treatments, patient will also get Bevacizumab (Avastin).
All Cause Mortality
	Neoadjuvant FOLFOX Plus Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Neoadjuvant FOLFOX Plus Bevacizumab
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Neoadjuvant FOLFOX Plus Bevacizumab
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Blood and lymphatic system disorders
Anemia	2/2 (100%)	19
Investigations
Alanine aminotransferase increased	1/2 (50%)	1
Aspartate aminotransferase increased	1/2 (50%)	2
Alkaline phosphatase increased	1/2 (50%)	2
White blood cell decreased	1/2 (50%)	4
Platelet count decreased	1/2 (50%)	4
Metabolism and nutrition disorders
Hypoalbuminemia	2/2 (100%)	4
Hypercalcemia	1/2 (50%)	1
Hyperglycemia	2/2 (100%)	13
Hyperkalemia	2/2 (100%)	2

Limitations/Caveats

Early termination lead to small numbers of subjects analyzed.

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.