Fluoropyrimidine, oxaliplatin and targeted receptor pre-operative therapy: a controlled trial in high-risk operable colon cancer

Phase 2

Completed

• Conditions: High risk, operable colon cancer; Cancer; Colon cancer

• Registration Number: ISRCTN87163246
• Lead Sponsor: niversity of Birmingham (UK)

Brief Summary

2012 Interim results article in http://www.ncbi.nlm.nih.gov/pubmed/23017669 Pilot/feasibility results results 2023 Results article in https://pubmed.ncbi.nlm.nih.gov/36657089/ (added 20/01/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2007-03-30
• Study Completion: 2019-12-31
• Last Update Posted: 30 January 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 1050

Inclusion Criteria

Current inclusion criteria as of 26/01/2018:
1. Histologically proven adenocarcinoma of the colon or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer
2. A candidate for adjuvant oxaliplatin/ fluoropyrimidine chemotherapy based on:
2.1. Either radiological high risk (rT4 or rT3 tumour with extramural extension = 5mm)
2.2. Or radiological intermediate risk (rT3 tumour with <5mm extramural extension) and younger age/good general health
3. Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma, and when recovered to a fitness level consistent with the other eligibility criteria
4. Adequate full blood count: WBC >3.0 x109/l; Plts >100 x109/l. Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
5. Adequate renal biochemistry: GFR >50 ml/min calculated by the Wright or Cockroft formula or EDTA clearance >70 ml/min
6. Adequate hepatobiliary function: bilirubin < 25 µmol/l (Patients with Gilbert’s syndrome who have raised bilirubin but otherwise normal liver function tests are eligible for the study.)
7. Aged 18 or over
8. WHO performance status of 0, 1 or 2
9. If female and of childbearing potential, must:
9.1. Have a negative pregnancy test =72hours prior to initiating study treatment
9.2. Agree to avoid pregnancy during and for 6 months after study treatment
10. If male with a partner of childbearing potential, must:
-Agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
11.Patient able and willing to provide written informed consent for the study

Previous inclusion criteria:
1. Histologically proven colon cancer with a radiological staging of T3, NX, M0
2. Computed Tomography (CT) scan criteria of poor prognosis (T4 or T3 and more than 5 mm extramural depth and/or probable nodal involvement and/or probable vascular invasion)
3. Fit for the neoadjuvant treatments
4. Patients who have presented with acute colonic obstruction if a successful defunctioning or stent procedure has been performed
5. Patients able and willing to provide written informed consent for the study

Exclusion Criteria

Current exclusion criteria as of 26/01/2018:
1. MorbidityAny patient for whom radiotherapy is advised by the MDT
2. Strong evidence of distant metastases or peritoneal nodules (M1)
3. Peritonitis (secondary to perforated tumour)
4. Colonic obstruction that has not been defunctioned
5. Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (<6 months) MI
6. Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
7. Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%

Additional exclusion criteria for panitumumab randomisation
1. RAS-mutant or unknown RAS status tumours
2. Allocated post-operative chemotherapy
3. History of interstitial pneumonitis or pulmonary fibrosis
4. History of severe or life-threatening hypersensitivity reactions
5. Serum magnesium levels within the normal range at trial entry (which can include intravenous correction)

Previous exclusion criteria:
1. Tumour within 15 cm of the anal verge as judged by sigmoidoscopy, or below the level of the sacral promontory, as judged by sagittal CT
2. Indication for radiotherapy
3. Evidence of disseminated disease (M1)
4. Peritonitis (secondary to perforated tumour)
5. Under the age of 18 or pregnant
6. Serious medical co-morbidity

Study & Design

• Study Type: Interventional
• Study Design: Not specified