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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Gefitinib, raltitrexed

• Study Type: Interventional
• Enrollment: 74
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Spain
  • A Coruna, Spain
    • Research Site
  • Barcelona, Spain
    • Research Site
  • Burgos, Spain
    • Research Site
  • Gijon, Spain
    • Research Site
  • Leon, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
  • Oviedo, Spain
    • Research Site
  • Pamplona, Spain
    • Research Site
  • Valladolid, Spain
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Determine the progression free survival

Secondary Outcome Measures

Outcome Measure
Determine objective tumor response

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Zanni MV, Foldyna B, McCallum S, Burdo TH, Looby SE, Fitch KV, Fulda ES, Autissier P, Bloomfield GS, Malvestutto CD, Fichtenbaum CJ, Overton ET, Aberg JA, Erlandson KM, Campbell TB, Ellsworth GB, Sheth AN, Taiwo B, Currier JS, Hoffmann U, Lu MT, Douglas PS, Ribaudo HJ, Grinspoon SK. Sex Differences in Subclinical Atherosclerosis and Systemic Immune Activation/Inflammation Among People With Human Immunodeficiency Virus in the United States. Clin Infect Dis. 2023 Jan 13;76(2):323-334. doi: 10.1093/cid/ciac767.
• Looby SE, Kantor A, Burdo TH, Currier JS, Fichtenbaum CJ, Overton ET, Aberg JA, Malvestutto CD, Bloomfield GS, Erlandson KM, Cespedes M, Kallas EG, Masia M, Thornton AC, Smith MD, Flynn JM, Kileel EM, Fulda E, Fitch KV, Lu MT, Douglas PS, Grinspoon SK, Ribaudo HJ, Zanni MV. Factors Associated With Systemic Immune Activation Indices in a Global Primary Cardiovascular Disease Prevention Cohort of People With Human Immunodeficiency Virus on Antiretroviral Therapy. Clin Infect Dis. 2022 Oct 12;75(8):1324-1333. doi: 10.1093/cid/ciac166.
• Zanni MV, Currier JS, Kantor A, Smeaton L, Rivard C, Taron J, Burdo TH, Badal-Faesen S, Lalloo UG, Pinto JA, Samaneka W, Valencia J, Klingman K, Allston-Smith B, Cooper-Arnold K, Desvigne-Nickens P, Lu MT, Fitch KV, Hoffman U, Grinspoon SK, Douglas PS, Looby SE. Correlates and Timing of Reproductive Aging Transitions in a Global Cohort of Midlife Women With Human Immunodeficiency Virus: Insights From the REPRIEVE Trial. J Infect Dis. 2020 Jul 9;222(Suppl 1):S20-S30. doi: 10.1093/infdis/jiaa214.

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: October 5, 2005
• First Submitted That Met QC Criteria: October 5, 2005
• First Posted (Estimate): October 7, 2005

Study Record Updates

• Last Update Posted (Estimate): December 18, 2007
• Last Update Submitted That Met QC Criteria: December 14, 2007
• Last Verified: December 1, 2007

More Information

Terms related to this study

• Keywords: Colorectal carcinoma advanced disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Gefitinib; Raltitrexed
• Other Study ID Numbers: 1839IL/0143