Oxaliplatin, Leucovorin, and Fluorouracil Before and After Radiation Therapy and Surgery in Treating Patients With Rectal Cancer That Can Be Removed by Surgery

NCT01263171 | Completed Phase 2 DMC

• 5 other identifiers: CDR0000691166WCTU-COPERNICUS2010-023083-40C23134/A11537CARDIFF-SPON830-10
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 7

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. PURPOSE: This phase II trial is studying giving oxaliplatin, leucovorin, and fluorouracil together, before and after radiation therapy and surgery in treating patients with rectal cancer that can be removed by surgery.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the rectum; stage IIIB rectal cancer; stage IIIC rectal cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who commence neoadjuvant chemotherapy and radiotherapy and then undergo surgical resection

  Two years

Secondary Outcomes (5)

• Feasibility in terms of achieved dose intensity for chemotherapy and radiotherapy

  Two years

• Safety in terms of NCI CTCAE v 4 toxicities up to 30 days postoperatively and late toxicity at 1 year after surgery

  Two years

• Complete response

  Two years

• Efficacy in terms of down-staging rectal cancer

  Two years

• Local recurrence-free, distant metastasis-free, and overall survival at 1 year after surgery

  Two years

Study Arms (1)

Neo-adjuvant chemotherapy

OTHER

Neo-adjuvant chemotherapy prior to short course pre-operative radiotherapy followed by adjuvant chemotherapy.

Drug: Leucovorin; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Procedure: therapeutic conventional surgery; Radiation: radiation therapy

Interventions

Leucovorin DRUG

Neo-adjuvant chemotherapy

fluorouracil DRUG

Neo-adjuvant chemotherapy

leucovorin calcium DRUG

Neo-adjuvant chemotherapy

oxaliplatin DRUG

Neo-adjuvant chemotherapy

adjuvant therapy PROCEDURE

Neo-adjuvant chemotherapy

neoadjuvant therapy PROCEDURE

Neo-adjuvant chemotherapy

therapeutic conventional surgery PROCEDURE

Neo-adjuvant chemotherapy

radiation therapy RADIATION

Neo-adjuvant chemotherapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histopathologically confirmed rectal adenocarcinoma meeting the following criteria: * Inferior aspect of tumor is \> 4 cm from anal verge on digital examination and pelvic MRI scan * Superior aspect of tumor is not higher than the anterior aspect of the S1/S2 interspace on pelvic MRI scan * Mesorectal fascia is not threatened or involved (tumor \> 1 mm from mesorectal fascia) * Primary tumor meets 1 of the following criteria: * T3a-b (mesorectal primary tumor invasion seen ≤ 5 mm beyond muscularis propria) in the presence of 1 of the following: * Extra-mural vascular invasion * Mesorectal lymph node(s)/tumor deposit(s) with irregular border and mixed signal intensity * Any T3c (primary tumor invasion seen \> 5 mm beyond muscularis propria)-T4a (invasion of visceral peritoneum for tumors with a component above peritoneal reflection) * Low tumors should not involve levator ani (\> 1 mm gap between tumor and levator ani) or anal sphincters * No evidence of distant metastases or stage T4b cancer with invasion into adjacent organs or structures * Must have measurable disease at the baseline visit * Impending rectal obstruction is permitted if relieved by a non-functioning ileostomy or colostomy * No disease threatening mesorectal fascia (disease ≤ 1 mm from mesorectal fascia whether this is primary tumor, extra-mural vascular invasion, or tumor deposit with irregular border and mixed signal intensity) PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Hemoglobin ≥ 9 g/dL * WBC ≥ 3 x 10\^9/L * Absolute neutrophil count ≥ 1.5 x10\^9/L * Platelet count ≥ 100 x10\^9/L * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 5 x ULN * AST or ALT ≤ 2.5 x ULN * Creatinine clearance ≥ 50 mL/min * Magnesium and calcium normal * Candidate for systemic therapy, in the opinion of the primary oncologist * No known significant impairment of intestinal absorption (e.g., chronic diarrhea, inflammatory bowel disease) * No evidence of established or acute ischemic heart disease (e.g., left bundle branch block, pathological q-waves, ST elevation, or ST-segment depression) and normal clinical cardiovascular assessment by ECG * No enlarged pelvic sidewall lymph nodes * No severe local bowel symptoms of tenesmus or irregularity or frequency of bowel habit precluding accurate assessment of diarrhea * No pelvic sepsis * No uncontrolled infection * Not pregnant or nursing * Fertile patients must use effective contraception during treatment and for 6 months after completion of treatment * No other prior or current malignant disease that, in the judgement of the treating investigator, is likely to interfere with study treatment or assessment of response * No clinically significant cardiovascular disease, including any of the following within the past year: * Myocardial infarction * Unstable angina * Symptomatic congestive heart failure * Serious uncontrolled cardiac arrhythmia * No history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease) PRIOR CONCURRENT THERAPY: * No prior pelvic radiotherapy * No metallic colon stent or rectal stent in situ * More than 30 days since prior chemotherapy, radiotherapy, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloproteinase inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibodies, or other experimental drugs

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cardiff University: lead
• Cancer Research UK: collaborator

Study Sites (7)

Walsgrave Hospital

Coventry, England, CV2 2DX, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

Rosemere Cancer Centre at Royal Preston Hospital

Preston, England, PR2 9HT, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, CF14 2TL, United Kingdom

Location

Glan Clwyd Hospital

Rhyl, Denbighshire, Wales, LL 18 5UJ, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Leucovorin; Fluorouracil; Oxaliplatin; Chemotherapy, Adjuvant; Neoadjuvant Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Simon Gollins, MD

  Glan Clwyd Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2010
• First Posted: December 20, 2010
• Study Start: April 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: September 21, 2016

Record last verified: 2016-09

Locations

GB (7)