Clinical trial to assess wether Lapatinib in association with Capecitabine and Radiation performs better than Capecitabine and Radiation in patients with localized rectal cancer

Active, not recruiting

• Conditions: Rectal cancer stage IIRectal cancer stage III; MedDRA version: 16.1Level: PTClassification code 10038050Term: Rectal cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.1Level: PTClassification code 10038049Term: Rectal cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001203-36-PT
• Lead Sponsor: Instituto Português de Oncologia do Porto Francisco Gentil, EPE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-13
• Last Update Posted: 10 March 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Age 18 years or above.
2. Diagnosis of adenocarcinoma of the rectum with the primary malignant lesion located between the dentate line up to 10cm of the anal verge by endoscopic examination.
3. KRAS mutational analysis of codon 12 and 13 without known activating mutations.
4. Clinical Stage II or III disease, according to AJCC Staging classification, 7th edition. For clinical staging the following procedures must have been conducted, within 4 weeks of treatment allocation:
4.1. Clinical History and Physical Examination,
4.2. Endoscopic ultrasound of the primary lesion,
4.3. Thoracic, abdominal and pelvic computed tomographic scan.
5. Clinically judged to be able to undergo curative resection of the rectal neoplasm despite pre-operative chemoradiotherapy.
6. Clinically judged to be able to undergo pelvic radiation therapy to a total dose of 50.4 Gy.
7. Signed informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Absence of baseline histological sample of the primary tumor.
2. Pregnant or lactating women.
3. Unwillingness or inability to comply with effective contraception, if the patient is fertile.
4. Impaired renal function defined as creatinine clearance < 60mL/min according to the Cockcroft-Gault formula.
5. Impaired hematological function: defined by any of the following on pre-treatment evaluation:
5.1. Hemoglobin concentration < 10.0 g/dL,
5.2. Absolute neutrophile count < 1 500 µL-1 and
5.3. Platelet count < 100 000 µL-1.
6. Impaired hepatic function defined by any of the following on pre-treatment evaluation:
6.1. Serum level of aspartate aminotransferase > 1.5 x ULN,
6.2. Serum level of alanine aminotransferase > 1.5 x ULN,
6.3. Serum level of alkaline phosphatase > 1.5 x ULN,
6.4. International Normalized Ratio > 1.5 and
6.5. Serum concentration of total bilirrubin > 1.5 x ULN.
7. Symptomatic heart failure or a left ventricular ejection fraction below the institution’s lower limit of normality as assessed through equilibrium radionuclide angiography.
8. Known intolerance to any of the study drugs.
9. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
10. Concurrent treatment with CYP3A4 inducers.
11. Concurrent treatment with CYP3A4 inhibitors.
12. Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel.
13. Currently enrolled in another clinical trial.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The trial’s objective is to show the superiority of Lapatinib and Capecitabine combination (arm A) over the standard Capecitabine (arm B);Secondary Objective: Not Applicable;Primary end point(s): The primary endpoint is pathologic complete remission. ;Timepoint(s) of evaluation of this end point: After surgical treatment.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Safety profile of the combination Lapatinib / Capecitabine / Radiation therapy in the pre-operative setting of patients with resectable rectal cancer.;Timepoint(s) of evaluation of this end point: Through-out the length of the trial until the end of study, 28 days after surgery.