Thalidomide and Tegafur/Uracil(UFUR) in the Treatment of Advanced Colorectal Cancer

Sponsor

National Cheng-Kung University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT00890188

Collaborator

(none)

Enrollment

Location

Arm

28.9

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Colorectal cancer is a major health problem in Western society contributing to a high mortality rate. Treatment options for the majority of patients with metastases are limited to cytotoxic chemotherapies. The first line chemotherapy containing with oxaliplatin is recommend by guideline. The use of antiangiogenic agents, either alone or in combination with other therapies may provide an alternative treatment modality in the management of these patients. Metronomic chemotherapy refers to the close, regular administration of a chemotherapeutic drug, over prolonged periods. The advantages of metronomic chemotherapy include reducing acute toxicities and sometimes surprisingly good activity against drug resistant tumors via antiangiogenic effect.

Thalidomide is an agent, which has shown potential in the treatment of hematological and solid tissue malignancies such as multiple myeloma via antiangiogenic mechanism. Tegafur/uracil (UFUR) is one of the effective chemotherapeutics reported to be an effective antiangiogenic agent in an animal model of metastatic colorectal cancers (CRCs).

In the present study, the investigators will try to use low dose metronomic schedule of thalidomide with tegafur/uracil regimen to see the anti tumor efficacy in recurrent and metastasis colorectal cancer patients after oxaliplatin-contained chemotherapy.

The primary endpoints are overall response rate and clinical benefit and the secondary endpoint were to determine the progression free survival, and duration of objective response, the overall survival (OS) and to assess the safety profile. This is a prospective phase II study. After having checked all eligibility criteria, patients will be treated with Tegafur/Uracil (TU) regimen. About 34 patients will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer	Drug: THALIDOMIDE and UFUR	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Feasibility of Combing THALIDOMIDE and UFUR in the Treatment of Advanced Colorectal Cancer After Oxaliplatin-Contained Chemotherapy

Study Start Date :

Jan 1, 2009

Anticipated Primary Completion Date :

Dec 1, 2010

Anticipated Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: THALIDOMIDE and UFUR	Drug: THALIDOMIDE and UFUR T: Thalidomide (50): 150 mg/d ((1# tid) U: UFUR(100) 300 mg/d (1# tid) 28 days for one cycle

Arm

Intervention/Treatment

Experimental: THALIDOMIDE and UFUR

Drug: THALIDOMIDE and UFUR

T: Thalidomide (50): 150 mg/d ((1# tid) U: UFUR(100) 300 mg/d (1# tid) 28 days for one cycle

Outcome Measures

Primary Outcome Measures

Overall response(CR+PR) and Clinical benefit (CR+PR+SD) [3 months]

Secondary Outcome Measures

To determine the progression free survival, overall survival (OS)and assess the safety profile [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed colorectal carcinoma
Patients must have received at least one oxaliplatin-contained chemotherapy before the study and did not want to receive or tolerate irinotecan- contained chemotherapy
Presence of at least one measurable disease which is defined as lesion that can be measured in at least 1 dimension as 20 mm with conventional CT or 10 mm with spiral CT scan
Age ≥ 18 year, ECOG performance status 0, 1, 2, 3
White blood cell (WBC) ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3 and hemoglobin ≥ 8 mg / dl
Serum creatinine level 2.0 mg/dL or lower
Serum bilirubin less than 1.5 times the upper limit of normal range (ULN)
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times the ULN if no demonstrable liver metastases or less than 5 times the ULN in the presence of liver metastases
Require to wait 28 days before entry onto the study after being treated with any immunotherapy, or biologic systemic (including any target therapy)
Written informed consent to participate in the trial

Exclusion Criteria:

Presence of CNS metastasis
Other malignancy with the exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to the entry of study
Less than 4 weeks since previous treatment
Concomitant illness that might be aggregated by chemotherapy. For examples, active, non-controlled infection or other active, non-controlled disease such as congestive heart failure, angina pectoris, respiratory insufficiency, arrhythmia. It depends on investigation's decision.
Women of child-bearing potential without using a reliable and appropriate contraceptive method during study period
Pre existent sensory or motor neurotoxicity > grade 2 according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) (disabling paresthesia and/or significant motor loss)
Patients who are receiving other concomitant chemotherapy, radiotherapy or any other investigational therapy