Roche trials database

Protocol number:

ML18601

Title of Study:

Phase IV clinical study of safety and tolerability of oral Xeloda (capecitabine) in adjuvant treatment of resected cancer of the colon.

Sponsor:

Roche Bulgaria EOOD

Company division:

Pharmaceutical

Product name:

Xeloda

Generic name:

capecitabine

Therapeutic area:

• Colorectal Cancer

Clinical study summary:

This nonrandomized, open-label, noncomparative, multicenter trial evaluated the safety and tolerability of oral Xeloda in adjuvant treatment of resected cancer of the colon. Patients received standard therapeutic cycles with an initial dose of Xeloda (1250 mg/m²) twice daily for 2 weeks followed by 1 week rest. Patients then received a further 8 therapeutic cycles unless there was evidence of unacceptable toxicity or relapse of the disease. Treatment was scheduled for 24 weeks.

Study center(s):

6 centers in Bulgaria

Phase of development:

IV

Objectives:

The objective of the study was to evaluate the safety and tolerability of oral Xeloda in adjuvant treatment of resected cancer of the colon.

Methodology:

After inclusion in the study, patients started receiving standard therapeutic cycles with an initial dose of Xeloda of 1250 mg/m² twice daily for 2 weeks followed by 1 week rest period without medication. After the baseline visit, study visits were scheduled according to the therapeutic cycles of Xeloda. At the baseline visit the following procedures were performed: anamnesis, physical exam, laboratory testing (hematology and differential WBC, and blood chemistry). At each subsequent visit the following were performed: physical exam, laboratory testing (hematology and differential WBC, and blood chemistry), and adverse events. In addition, on Week 6 and 18 the following procedures were performed: tumor markers (CA/CA 19-9); and on Week 28: physical exam, tumor markers (CA/CA 19-9), chest X-ray, and CT scan (only for high-risk patients). Patients visited the investigators at the end of the nontreatment week before the next cycle. Laboratory assessments were performed and the drug for the next cycle was dispensed. The last visit (follow-up) was scheduled 4 weeks after the last dose of Xeloda was taken.

Number of patients (planned/analyzed):

70 planned; 63 enrolled and treated.

Diagnosis and main criteria for inclusion:

Male and female patients ≥18 years with histologically confirmed colon carcinoma with curative surgery not less than 4 and not more than 8 weeks prior to study inclusion, an Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and life expectancy >3 years.

Test product, dose and mode of administration or test procedure:

Xeloda 1250 mg/m² twice daily subcutaneous injection

Duration of treatment:

24 weeks

Reference therapy, dose and mode of administration or reference procedure:

N/A

Criteria for evaluation (efficacy, safety):

Safety: Percentage of patients with any adverse event (AE); degree of AE; percentage of patients with serious adverse events (SAEs); percentage of patients with dose reduction or delay of treatment cycles due to toxicity.

Tolerability: Percentage of patient withdrawal due to intolerance of investigational drug.

Statistical methods:

Descriptive statistics were used to summarize the incidence and frequency of AEs.

Summary (efficacy, safety, other results):

Safety: Of the 63 patients studied, 48 (76%) completed the full course of treatment and the remaining 15 (24%) were withdrawn from treatment for various reasons. A total of 115 AEs was observed. Most of the AEs (108) were non serious (approximately 93.9% of all AEs); 57 (49.6%) were strongly associated with the study drug. A "probable" causal association was considered for 27 (23.5%) AEs and a "possible" causal association was considered in 19 (16.5%) AEs. The majority of adverse events were mild to moderate in intensity - 59 (51.3%) were “mild”, 44 (38.3 % ) were “moderate”; 9 (7.8%) were “severe” and 1 (0.9%) was “life threatening”; 2 (1.7%) AEs were without information with regards to their grade. SAEs were observed for 5 (8.9%) patients. AEs included elevated ALT (severe, no relation to the study drug), diarrhea (severe, related to study drug), vomiting (severe, related to study drug), acute heart failure (leading to death). Forty-three of 56 patients (76.8%) developed an AE. Patients with serious adverse events were significantly lower - about 9 (5%) patients. A possible relationship with the study drug was observed in 80% of the AEs. Seventy-five percent of AEs were resolved, 9% were resolved with sequelae and 12% were unresolved. One of the AEs became serious and led to death.

The most common observed AEs were as follows: hand-foot syndrome (25.2%), nausea (13.0%), diarrhea (13.0%), hyperbilirubinemia (7.0%), abdominal pain (6.1%), elevated ALT (4.3%), vomiting (4.3%), elevated AST (3.5%), headache (12.5%), hepatic steatosis (1.7%), anemia (1.7%), skin toxicity (1.7%), acute heart failure (0.9%), disease progression (peritoneal metastasis) (0.9%), thrombocytopenia (0.9%), deforming spondylosis of the spinal vertebra (0.9%).
In 4 patients (6.3 %) out of 63 the treatment was interrupted due to AEs. The most common AEs leading to interruption were as follows: diarrhea (4; 25%), hand-foot syndrome (3 AEs), vomiting (3 AEs), abdominal pain (2 AEs). AEs caused a greater impact on dose correction. During the third cycle of therapy, 10 cases (18%) were observed. For all other cycles, the percentage of patients who did not require dose modification was more than 85 percent.

The most common reasons for withdrawal were "Side effect" and "lack of cooperation from the patient” - with four patients (6.3%). For two patients (3.2%) the reason for withdrawal was "inadequate therapeutic response”. Two patients did not complete due to "violation of selection criteria at the beginning”, one of them because of “metastases of the anterior abdominal wall” and the other because of "treatment with Clexane Fintrome". One patient in each group (1.6% of all surveyed) refused treatment.

Conclusions:

Overall treatment was well tolerated.

Date of report:

01.01.2009

Click here for the protocol registry listing of this trial.