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A Phase III Trial of Modified FOLFOX6 Versus CAPOX, With Bevacizumab (NSC-704865) or Placebo, as First-Line Therapy in Patients With Previously Untreated Advanced Colorectal Cancer


Phase 3
18 Years
N/A
Not Enrolling
Both
Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage III Colon Cancer, Stage III Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

Thank you

Trial Information

A Phase III Trial of Modified FOLFOX6 Versus CAPOX, With Bevacizumab (NSC-704865) or Placebo, as First-Line Therapy in Patients With Previously Untreated Advanced Colorectal Cancer


OBJECTIVES:

I. Compare overall survival in patients with locally advanced, metastatic, or recurrent
colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and
bevacizumab vs capecitabine, oxaliplatin, and bevacizumab.

II. Compare progression-free survival and time to treatment failure in patients treated with
these regimens.

III. Compare the response of patients with measurable disease treated with these regimens.

IV.Compare toxicity rates of these regimens in these patients. V. Compare patient-reported
functional status and convenience of therapy in patients treated with these regimens.

VI. Correlate germline polymorphisms of DNA repair (e.g., ERCC-1, XRCC1, GST-P1, XPD, and
ribonucleotide reductase), target enzymes (e.g., thymidylate synthase, dihydropyrimidine
dehydrogenase, and thymidine phosphorylase), angiogenesis (e.g., vascular endothelial growth
factor), and growth factors (e.g., epithelial growth factor receptor) with survival,
progression-free survival, and toxicity from chemotherapy in patients treated with these
regimens.

VII. Correlate tumor mRNA expression levels of similar DNA repair enzymes as well as enzymes
involved in angiogenesis with survival and progression-free survival in patients treated
with these regimens.Correlate tumor mRNA expression levels of similar target enzymes before
treatment with survival, progression-free survival, and toxicity in patients treated with
these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
Zubrod performance status (0 or 1 vs 2) and prior adjuvant therapy (yes vs no). Patients are
randomized to 1 of 2 treatment arms.

ARM I: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours
on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients are
further randomized to receive bevacizumab or placebo* IV over 30-90 minutes on day 1.
Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive
bevacizumab.

ARM II: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine on days
1-15. Patients are further randomized to receive bevacizumab or placebo* as in arm I.
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
NOTE: *As of 11/15/04, placebo is no longer part of treatment plan; all patients receive
bevacizumab.

Patients are followed every 3 months until disease progression. After disease progression,
patients are followed every 6 months for 2 years and then annually for up to 4 years after
study entry.

PROJECTED ACCRUAL: A total of 2,200 patients (1,100 per treatment arm) will be accrued for
this study within 3 years.


Inclusion Criteria:



- Histologically or cytologically confirmed locally advanced, recurrent, or metastatic
colorectal adenocarcinoma

- Not curable by surgery or amenable to radiotherapy with curative intent

- Previously resected colorectal cancer with new evidence of metastasis does not
require separate histologic or cytologic confirmation unless one of the
following is true:

- More than 5 years has elapsed between primary surgery and development of
metastatic disease

- Primary tumor was T1-T2, N0, M0

- Site of primary lesion must be or have been in the large bowel as determined by
endoscopy, radiology, or surgery

- Measurable or evaluable disease

- No known brain or leptomeningeal disease

- Performance status - Zubrod 0-2

- No history of hemorrhagic or thrombotic disorders

- Absolute neutrophil count greater than 1,500/mm^3

- Platelet count greater than 100,000/mm^3

- Bilirubin no greater than 2.0 times upper limit of normal (ULN)

- SGOT no greater than 2.5 times ULN (5 times ULN for patients with liver involvement)

- Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN for patients with
liver involvement or 10 times ULN for patients with bone involvement)

- INR no greater than 1.5

- PTT no greater than ULN

- Creatinine no greater than 1.5 times ULN

- Creatinine clearance at least 50 mL/min

- Proteinuria less than 1+*

- Protein less than 500mg/24 hours*

- No uncontrolled hypertension

- Hypertension must be well-controlled (i.e., less than 160/90) and on a stable
regimen of antihypertensive therapy

- No unstable angina

- No symptomatic congestive heart failure

- No myocardial infarction within the past 6 months

- No serious uncontrolled cardiac arrhythmia

- No New York Heart Association class III or IV heart disease

- No symptomatic pulmonary fibrosis

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated
stage I or II cancer currently in complete remission

- No active or uncontrolled severe infection

- No contraindication to oral medications (e.g., severe dysphagia)

- G-tubes or J-tubes allowed

- No peripheral neuropathy greater than grade 1

- No serious non-healing wound, ulcer, or bone fracture

- No significant traumatic injury within the past 28 days

- No other severe acute or chronic medical condition or laboratory abnormality that
would preclude study participation

- No psychiatric condition that would preclude study participation

- No prior bevacizumab

- No prior oxaliplatin

- No prior chemotherapy for advanced colorectal cancer

- Prior adjuvant therapy for resected stage II-III disease allowed provided at
least 12 months have elapsed between completion of therapy and diagnosis of
recurrent disease

- At least 28 days since prior radiotherapy and recovered

- See Disease Characteristics

- More than 28 days since prior major surgical procedure or open biopsy

- More than 7 days since prior fine needle aspiration or core biopsy

- No concurrent major surgery

- More than 10 days since prior full-dose aspirin (325 mg)

- No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or
cilostazol)

- No other concurrent investigational agents

- No concurrent therapeutic anticoagulation

- Prophylactic anticoagulation of central venous lines allowed

- Low-dose prophylactic enoxaparin or heparin allowed

- No concurrent cimetidine

- No concurrent sorivudine or its related analogs (e.g., brivudine)

- No concurrent use of a cold cap or iced mouth rinses

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Overall survival in patients with colorectal cancer treated with fluorouracil/leucovorin calcium and oxaliplatin with and without becavizumab versus those treated with capecitabine and oxaliplatin with our without bevacizumab

Outcome Description:

Will be analyzed primarily by the stratified Cox model.

Outcome Time Frame:

Up to 6 years

Safety Issue:

No

Principal Investigator

Charles Blanke

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02556

NCT ID:

NCT00070122

Start Date:

April 2004

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage III Colon Cancer
  • Stage III Rectal Cancer
  • Stage IV Colon Cancer
  • Stage IV Rectal Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms

Name

Location

Southwest Oncology GroupSan Antonio, Texas  78245