Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy and Bevacizumab With or Without Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
No phase specified	Treatment	Active	18 and over	NCI	MSKCC-07021 07-021, NCT00462501

Objectives

Primary

1. Determine whether neoadjuvant chemotherapy comprising oxaliplatin, fluorouracil, leucovorin calcium (FOLFOX), and bevacizumab can be substituted for pelvic radiotherapy without compromising R0 resection rates in patients with locally advanced rectal cancer.

Secondary

1. Determine whether a 3-year local recurrence rate of ≤ 10% can be achieved in patients treated with this regimen.
2. Determine the proportion of patients who achieve a complete pathologic response after treatment with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically or pathologically confirmed adenocarcinoma of the rectum
  • Clinical stage T1, N1; T2, N1; T3, N0; or T3, N1 by endorectal ultrasonography (ERUS)
    • No bulky N2 disease by either ERUS or MRI
    • No primary fixed or unresectable (clinical stage T4) rectal cancer or recurrent colorectal cancer limited to the pelvis
      • Primary unresectable rectal cancer is defined as a primary rectal tumor which on the basis of either physical exam, ERUS or pelvic MRI is deemed to be adherent or fixed to adjacent pelvic structures



• Must be a candidate for all of the following:
  • Neoadjuvant chemoradiotherapy
  • Systemic therapy with flourouracil, leucovorin calcium, oxaliplatin (FOLFOX), and bevacizumab
  • Complete surgical resection via low anterior resection prior to administration of any therapy



• No low-lying tumors deemed to require an abdominal perineal resection



• No large or bulky tumors that require a diverting colostomy or placement of an endorectal stent prior to treatment initiation



• No clinical evidence of metastatic disease

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior chemotherapy or surgery for rectal cancer
• No prior pelvic radiotherapy
• No other concurrent experimental therapy, including any of the following:
  • Chemotherapy
  • Radiotherapy
  • Hormonal therapy
  • Antibody therapy
  • Immunotherapy
  • Gene therapy
  • Vaccine therapy
  • Angiogenesis inhibitors
  • Matrix metalloprotease inhibitors
  • Thalidomide
  • Anti-vascular endothelial growth factor/Flk-1 monoclonal antibody
  • Any other experimental drugs

Patient Characteristics:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count > 150,000/mm³
• Hemoglobin > 8.0 g/dL
• Creatinine ≤ 1.5 times upper limit of normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after completion of study therapy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No arterial thrombotic event within the past 6 months, including stable or unstable angina, myocardial infarction (MI), or cerebral vascular accident (CVA)
  • Deep venous thrombosis, pulmonary embolus, MI, CVA, atrial fibrillation, or any other conditions occurring more than 6 months ago allowed provided patient is on stable doses of anticoagulant therapy
• No other medical or psychiatric condition or disease that would preclude study therapy

Expected Enrollment

A total of 36 patients will be accrued for this study.

Outcomes

R0 resection rate

3-year local recurrence rate of ≤ 10%
Complete pathologic response
Disease-free survival
Overall survival

Outline

This is a non-randomized, open-label, pilot study.

• Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and bevacizumab IV over 10 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 1 and 2 in weeks 1, 3, 5, and 7. Patients then receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 48 hours on days 1 and 2 in weeks 9 and 11. Treatment continues in the absence of disease progression or unacceptable toxicity.

  Within 3 weeks after completion of neoadjuvant chemotherapy, patients undergo restaging evaluation. Patients with no evidence of disease progression by endorectal ultrasound (ERUS), pelvic MRI, and CT scan of the chest/abdomen AND who remain candidates for R0 resection may proceed directly to surgical resection within 4-6 weeks after completion of neoadjuvant chemotherapy. Patients with progressive disease who are not candidates for an R0 resection, proceed to neoadjuvant chemoradiotherapy.




• Neoadjuvant chemoradiotherapy: Patients undergo pelvic radiotherapy 5 days a week and receive concurrent fluorouracil IV continuously for 5½ weeks. Within 4-7 weeks after completion of chemoradiotherapy, patients undergo surgical resection.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 5 years.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Leonard Saltz, MD, Principal investigator		Ph: 212-639-2501; 800-525-2225
Karyn Goodman, MD, Principal investigator		Ph: 212-639-3983 ; 800-525-2225
Martin Weiser, MD, Principal investigator		Ph: 212-639-6698; 800-525-2225 Email: weiser1@mskcc.org

U.S.A.
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Leonard Saltz, MD	Ph:  212-639-2501 800-525-2225

See All Trial Sites

Registry Information
Official Title		A Pilot Study of Neoadjuvant Chemotherapy with Selective Use of Radiation for Locally Advanced Rectal Cancer
Trial Start Date		2007-03-20
Trial Completion Date		2009-12-01 (estimated)
Registered in ClinicalTrials.gov		NCT00462501
Date Submitted to PDQ		2007-03-15
Information Last Verified		2008-12-14
NCI Grant/Contract Number		CA08748