A study comparing chemotherapy given before or after radiation in patients with rectal cancer

Phase 2

Not yet recruiting

• Conditions: Carcinoma Rectum

• Registration Number: CTRI/2015/01/005385
• Lead Sponsor: Cancer Institute WIA

Brief Summary

Patients with locally advanced rectal cancers who are at a high risk of distant metastases are not exposed to systemic doses of chemotherapy until very late in the treatment schedule using the current standard of care of neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Hence, earlier incorporation of chemotherapy either in the neoadjuvant or interval setting may improve tumor response and as a consequence, the overall survival.

The **INNOVA** trial (Interval or NeOadjuVAnt chemotherapy in rectal cancer) is designed to evaluate two pre-operative regimens in locally advanced high-risk rectal cancers (neoadjuvant and interval chemotherapy with capecitabine plus oxaliplatin) in a single-center randomized open-label phase II trial. We seek to evaluate the efficacy of these two pre-operative regimens as determined by the primary end-point, pCR rate and to evaluate the toxicity of these regimens. The regimen with a better pCR rate could be considered for comparison with the current standard of care in a future randomized phase III trial. If both the regimens have an identical pCR rate, then the one with a favourable toxicity profile would be considered for further evaluation.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

An optimal Simon’s two-stage design will be used to calculate sample size in order to terminate an ineffective arm early in the study. The pCR rates for the current standard of chemoradiation with capecitabine varies from 7% to 14% (14,27,55). Hence, the experimental regimens, a pCR of 5% is considered unacceptable (p0) whereas a pCR of 20% is considered acceptable (p1). In the first stage, 21 patients will be recruited in each arm. If ≤1 pCR is observed in any arm, then that arm of the study will be terminated and it will be concluded that that arm should not be pursued. If ≥2 pCR is observed in both arms, then both arms will be carried to the second stage where an additional 20 patients will be recruited in each arm. Thus, with a sample size of 41 patients per arm, the Type I error amounts to 5% and Type II error will be 10%. If ≥5 pCR is observed in any arm, then that arm will be considered suitable for further investigation. This design ensures a 90% probability of correctly selecting the more effective treatment when there is an absolute difference in the pCR rates of at least 15% between the two experimental treatment arms. If both arms have similar responses, then other factors like adverse effects, compliance and feasibility will be considered to select a regimen to pursue for further investigation. After accounting for a 15% drop-out rate, a total sample size of **94 patients (47 per arm)** would be targeted.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-15
• Last Update Posted: 2015-12-01

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 94

Inclusion Criteria

â—Histopathologically confirmed adenocarcinoma of the lower and middle third rectum, with the lower edge of the tumor within 12 cm from the anal verge â—Age 18 to 70 years â—ECOG performance status 0-2 â—Locally advanced tumor defined as presence of any one of the following on high-resolution thin slice (3mm) MRI: -Involved or threatened CRM (tumor or node extends to ≤2mm of or beyond the mesorectal fascia) -Any T3 tumor in the lower rectum (within 6 cm from anal verge), T3c or T3d in mid rectum (ie-tumor extending >5mm beyond the muscularis propria) -Resectable T4 -T3/T4 N1 or T1-T4 N2 -Extramural vascular invasion â—No evidence of established distant metastasis â—Adequate haematological, liver and renal function (WBC >3 x 109/L, neutrophils >1.5 x 109/l and platelets >100 x 109/L; serum creatinine ≤1 x upper limit of normal or creatinine clearance >50ml/min; serum bilirubin <1.5 x upper limit normal and liver transaminases and alkaline phosphatase <3 x upper limit normal) â—Normal clinical cardiovascular assessment â—Willing and able to give informed consent and comply with treatment schedule.

Exclusion Criteria

• â—Disease outside the mesorectal envelope (internal iliac/ lateral pelvic lymph nodes) â—Previous radiotherapy to the pelvis â—Previously received chemotherapy for the currently diagnosed cancer â—Synchronous colorectal or other malignancies â—Active stable or unstable angina, NYHA class 2 congestive cardiac failure, myocardial infarction in the past 1 year, acute coronary syndrome even if controlled, arrhythmias â—Serious uncontrolled intercurrent illness including uncontrolled hypertension or poorly controlled diabetes mellitus â—Patients with a history of previous malignancy in the past 5 years, excepting basal or squamous cell skin cancer or cervical carcinoma-in-situ.
• â—Known HIV, HBV or HCV infection â—Pregnant or lactating women or premenopausal women not using adequate contraception â—Patients with any other condition or concurrent medical or psychiatric disease who, in the opinion of the investigator, is not eligible to enter the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
pathological complete response (pCR) [defined as absence of any detectable residual tumor cells in the resected specimen]	completion of surgery

Secondary Outcome Measures

Name	Time	Method
Frequency and severity of adverse events (AE) during chemotherapy [National Cancer Institute’s common toxicity criteria] and chemoradiation [using Radiation Therapy Oncology Group’s toxicity criteria]	end of chemoradiation and end of chemotherapy
Surgical complications: intra-operative and 30-day postoperative [according to Dindo score]	during surgery and till 30 days after surgery
Microscopic R0 resection rate [defined as negative resection margins including circumferential margin (CRM)]	-Circumferential margin (CRM) involvement [defined as tumor ≤1mm from the inked circumferential margin]
Complicance to treatment	at end of treatment

Trial Locations

Locations (1)

Cancer Institute (WIA); 🇮🇳 Chennai, TAMIL NADU, India

Cancer Institute (WIA)

🇮🇳Chennai, TAMIL NADU, India

Ramakrishnan A S

Principal investigator

044-22209150

ram_a_s@yahoo.com