A Phase 2 Study of Tomudex & Iressa as Second Line Chemotherapy in Subjects With Colorectal Carcinoma

A Randomized, Placebo-Controlled, Double-Blind Phase 2b Study of Raltitrexed (Tomudex) and ZD1839 (Iressa) Versus Raltitrexed Alone as Second Line Chemotherapy in Subjects With Colorectal Carcinoma

The primary objective of this study is to compare the activity of raltitrexed and ZD1839 versus raltitrexed alone as second line chemotherapy in subjects with colorectal carcinoma by estimating progression free survival (PFS) in each treatment arm.

Inclusion Criteria:

• Male or female, aged 18 to 75 years, inclusive
• histologically-confirmed metastatic colorectal carcinoma; measurable lesion according to the Response Evaluation Criteria in Solid Tumours (RECIST)
• relapsed after treatment with a fluoropyrimidine-based chemotherapy
• prior chemotherapeutic regimen for metastatic or locally advanced disease with an interval of at least 4 weeks between the last administration of chemotherapy an the first administration of study treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• life expectancy of at least 12 weeks

Exclusion Criteria:

• Known severe hypersensitivity to raltitrexed or any of the excipients of this product
• known severe hypersensitivity to raltitrexed or any of the excipients of this product
• active infection or uncontrolled diarrhoea
• cerebral metastasis or meningeal carcinomatosis
• any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
• simultaneous antitumoral treatment
• radiotherapy within 2 weeks before entry into the study
• other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
• any unresolved chronic toxicity greater than common toxicity criteria (CTC) grade 2 from previous anticancer therapy (except alopecia)
• significant clinical disorder or laboratory finding (leukocyte count less than 3.0 x 109 /litre (L) or platelets less than 100 x 109 /L; serum total bilirubin more than 2.0 mg/dl; as judged by investigator, any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease); creatinine clearance ≥ 65ml/min (according to Cockcroft-Gault formula); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times the upper limit of the reference range (ULRR) if no demonstrable liver metastases, or greater than 5 times the ULRR in the presence of liver metastases)
• pregnancy or breast feeding (women of child-bearing potential)
• concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or ST John's Wort;
• Treatment with a non- approved or investigational drug within 30 days before Day 1 of study treatment