Fluorouracil and Oxaliplatin With or Without Panitumumab In Treating Patients With High-Risk Colon Cancer That Can Be Removed by Surgery

• Status: Unknown status
• Trial end date: 2019-12-31
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective with or without panitumumab in treating patients with colon cancer.

PURPOSE: This randomized phase III trial assessing whether preoperative chemotherapy and/or an anti-EGFR monoclonal antibody improve outcome in high risk operable colon cancer.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Birmingham
• Treatments: Capecitabine; Fluorouracil; Oxaliplatin; Panitumumab

Criteria

INCLUSION CRITERIA

• Histologically proven adenocarcinoma of the colon or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer.

• A candidate for adjuvant oxaliplatin/ fluoropyrimidine chemotherapy based on:

• Either radiological high risk (rT4 or rT3 tumour with extramural extension ≥ 5mm)

• Or radiological intermediate risk (rT3 tumour with <5mm extramural extension) and younger age/good general health

• 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

• 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.

• Adequate renal biochemistry: GFR >50 ml/min calculated by the Wright or Cockroft formula or EDTA clearance >70 ml/min

• 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.)

• Aged 18 or over

• WHO performance status of 0, 1 or 2

• If female and of childbearing potential, must:

• Have a negative pregnancy test ≤72hours prior to initiating study treatment

• Agree to avoid pregnancy during and for 6 months after study treatment

• 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

• Patient able and willing to provide written informed consent for the study

EXCLUSION CRITERIA

• Any patient for whom radiotherapy is advised by the MDT

• Strong evidence of distant metastases or peritoneal nodules (M1)

• Peritonitis (secondary to perforated tumour)

• Colonic obstruction that has not been defunctioned

• Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (<6 months) MI

• Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery

• 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

• RAS-mutant or unknown RAS status tumours

• Allocated post-operative chemotherapy

• History of interstitial pneumonitis or pulmonary fibrosis

• History of severe or life-threatening hypersensitivity reactions

• Serum magnesium levels within the normal range at trial entry (which can include intravenous correction)