NIH Clinical Research Studies

Protocol Number: 03-C-0300

Active Accrual, Protocols Recruiting New Patients

Title:
A Phase II Randomized Trial Comparing TNFerade[TM] Biologic with Capecitabine and Radiation Therapy Followed by Surgical Resection Versus Capecitabine and Radiation Therapy Followed by Surgical Resection for the Treatment of Rectal Cancer
Number:
03-C-0300
Summary:
This study will evaluate the effectiveness of the experimental drug, TNFerade[TM], in combination with radiation therapy and capecitabine, a chemotherapy drug, before surgery to remove cancer. Up to 95 patients will participate over a 3-year period in this study. They will be assigned at random to two groups: those to receive TNFerade[TM], capecitabine, and radiation therapy; and those to receive capecitabine and radiation therapy. TNFerade[TM] is a modified live virus called an adenovirus, normally causing an illness similar to a cold.

Patients ages 18 or older with Stage II or III cancer and who do not have a history of serious heart disease may be eligible for this study. Patients will undergo a physical examination and blood collection. Before patients are assigned randomly to groups, 10 will be treated with 4 x(10)10 pu, a dose level of TNFerade[TM], followed by chemotherapy with capecitabine and radiation, to evaluate the drug and determine whether the tumor can be removed by surgery. Then two patient groups will be assigned to receive the drug before administration of chemotherapy and radiation: one with a dose of 4 x(10)10 pu, and the other with 4 x(9)10 pu. TNFerade[TM] will be injected into four sections of the tumor. There will be four biopsies done of the tumor, one before the treatment is given, and then at three other stages. All patients will receive additional chemotherapy after the tumor is removed through surgery, and all will receive radiation therapy to the tumor 5 days a week, over a period of 5 to 7 weeks. All patients will receive capecitabine orally twice a day during the weeks of radiation therapy. During chemotherapy treatment, about 2 tablespoons of blood will be drawn for examination. If patients develop side effects, the dose of capecitabine may be reduced or delayed. Blood levels will be measured for TNFerade[TM] as well.

Following completion of 5 weeks of chemotherapy and radiation, patients will have a 4-week rest. If a physical exam and lab results show that it is safe to proceed with surgery, patients will be scheduled for surgery at the Clinical Center. Then about 3 weeks after surgery, patients will return to NIH for a blood test and a computed tomography (CT) scan to see if the tumor has returned and to watch for side effects from treatment. If there is no sign of the tumor, patients will begin standard chemotherapy with appropriate drugs. If not all of the tumor has been removed, there may be additional radiation therapy or surgery. Patients will be asked to return to NIH every 3 months for up to 3 years, for a CT scan and lab tests.

Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled
Gender: Male & Female
Referral Letter Required: Yes
Population Exclusion(s): None

Eligibility Criteria:
INCLUSION CRITERIA:

All patients greater than or equal to 18 years old who have biopsy proven T3 or T4 rectal cancer with or without regional lymph node involvement, or patients with a locally recurrent rectal cancer. Rectal cancer will be defined as any adenocarcinoma of the rectum located below the peritoneal reflection excluding Paget's disease of the anus. The T status will be ascertained by transrectal ultrasound when possible. Patients with obstructive/circumferential lesions will be staged by CT scan and clinical exam.

Patients must be willing to return for follow-up.

Patients must be able to give and sign informed consent.

Patients must be suitable candidates for surgical resection post-chemoradiation, i.e. no history of severe congestive heart failure or severe pulmonary disease.

ECOG less than or equal to 2.

Life expectancy greater than 6 months.

EXCLUSION CRITERIA:

Patients with evidence of widely metastatic disease.

{Note: patients with low volume metastatic disease that can be resected or ablated to make the patient clinically NED will not be excluded- e.g.1-2 pulmonary lesions or 1-2 liver lesions}.

Any of the following hematologic abnormalities:

a. HGB less than 8.0 gm/dL unable to be corrected with a transfusion.

b. Absolute neutrophil count (ANC) less than 1500 cells/mm(3).

c. Platelets less than 100,000/mm(3).

d. APTT ratio or INR greater than 1.5 (except in patients who are therapeutically anticoagulated for non-related medical conditions such as atrial fibrillation and whose anti-thrombotic treatment can not be withheld for vector injection or surgery).

A history of hepatic cirrhosis or present hepatic dysfunction with:

a. Total bilirubin greater than 2.0 mg/dL except for patients with Gilbert's syndrome who must have a direct bilirubin less than or equal to 1.0 mg/dL.

b. AST/ALT greater than or equal to 2.5 times upper limit of normal.

Renal insufficiency as determined by a serum creatinine greater than 2.0 mg/dL.

Patients may not have received prior radiation therapy for their rectal cancer.

Patients may not have received any systemic chemotherapy or biologic therapy within 30 days prior to enrollment and must have recovered from all significant toxicities.

Significant history of a medical problem that would preclude the patient from undergoing an operative procedure such as a history of severe congestive heart failure or active ischemic heart disease.

Concurrent second malignancy requiring systemic therapy.

Pregnant or lactating women, or men/women unable or unwilling to practice contraception.

Chronic systemic corticosteroid use.

Patients with history of deep venous thrombosis or pulmonary embolus.

Patients with Doppler evidence of deep venous thrombosis at screening.

Known history of documented coagulopathy or thrombophillic disorders.

Hormone replacement therapy (within one month prior to Day 1).

Known history of documented cerebrovascular disease, stroke or TIA.

Surgery within the last 1 month (excluding diverting colostomy or iliostomy for obstruction).

Special Instructions:
Currently Not Provided
Keywords:
Pathologic Complete Response
Disease Free Survival
Overall Survival
Gene Expression
Proteomic Profiles
Recruitment Keyword(s):
Rectal Cancer
Condition(s):
Rectal Neoplasms
Investigational Drug(s):
TNFerade TM
Investigational Device(s):
None
Intervention(s):
Drug: TNFerade TM
Supporting Site:
National Cancer Institute

Contact(s):
NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):
Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin. 2002 Jan-Feb;52(1):23-47. Erratum in: CA Cancer J Clin 2002 Mar-Apr;52(2):119. CA Cancer J Clin 2002 May-Jun;52(3):181-2.

Chari RS, et al, Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surg. 1995 Jun;221(6):778-86; discussion 786-7.

Grann A, et al, Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer. Dis Colon Rectum. 1997 May;40(5):515-22.

Active Accrual, Protocols Recruiting New Patients

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