Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation. The RAPIDO Trial
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Colorectal Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/10/2017 |
| Start Date: | June 21, 2011 |
| End Date: | June 8, 2022 |
Randomized Multicentre Phase III Study of Short Course Radiation Therapy Followed by Prolonged Pre-operative Chemotherapy and Surgery in Primary High Risk Rectal Cancer Compared to Standard Chemoradiotherapy and Surgery and Optional Adjuvant Chemotherapy.
Currently the 3-year disease free survival of patients with locally advanced rectal cancer
is about 50%. Current standard treatment for patients at high risk of failing locally and/or
systemically includes pre-operative long course radiotherapy (5 weeks) in combination with
chemotherapy (so called neoadjuvant chemoradiotherapy). The neoadjuvant chemoradiotherapy
has been demonstrated to improve local control, but had no effect on the overall survival.
Different studies in patients with rectal cancer studying the effect of adjuvant post
operative chemotherapy did not result in an improved survival. This may be due the fact that
rectal cancer surgery (TME) is associated with a high complication rate so substantial
proportion of patients cannot receive chemotherapy postoperatively. An alternative approach
is to administer the systemic therapy preoperative. To guarantee control of the rectum tumor
short-course radiotherapy (5 days) is given, as different studies showed local control of
the tumor for a long time. During this waiting period the patient is in a good condition to
receive an optimal dose of chemotherapy. The investigators hypothesize that with this
proposed protocol both the local tumour and possible micrometastases are effectively treated
and that this will result in an increased survival. The investigators will compare this with
the standard treatment of neoadjuvant chemoradiation followed by TME surgery and optional
adjuvant chemotherapy.
is about 50%. Current standard treatment for patients at high risk of failing locally and/or
systemically includes pre-operative long course radiotherapy (5 weeks) in combination with
chemotherapy (so called neoadjuvant chemoradiotherapy). The neoadjuvant chemoradiotherapy
has been demonstrated to improve local control, but had no effect on the overall survival.
Different studies in patients with rectal cancer studying the effect of adjuvant post
operative chemotherapy did not result in an improved survival. This may be due the fact that
rectal cancer surgery (TME) is associated with a high complication rate so substantial
proportion of patients cannot receive chemotherapy postoperatively. An alternative approach
is to administer the systemic therapy preoperative. To guarantee control of the rectum tumor
short-course radiotherapy (5 days) is given, as different studies showed local control of
the tumor for a long time. During this waiting period the patient is in a good condition to
receive an optimal dose of chemotherapy. The investigators hypothesize that with this
proposed protocol both the local tumour and possible micrometastases are effectively treated
and that this will result in an increased survival. The investigators will compare this with
the standard treatment of neoadjuvant chemoradiation followed by TME surgery and optional
adjuvant chemotherapy.
Patients will be randomized between an experimental group (arm B) in which short course 5 x
5 Gy radiation scheme is followed by six cycles of combination chemotherapy
(capecitabine/5FU and oxaliplatin) and surgery and a control group (arm A) with long course
chemoradiotherapy followed by surgery. In arm A adjuvant chemotherapy is allowed according
to the local protocol of the institution. In both groups the rectal tumour will be removed
by TME surgery or more extensive surgery if required because of tumour extent.
5 Gy radiation scheme is followed by six cycles of combination chemotherapy
(capecitabine/5FU and oxaliplatin) and surgery and a control group (arm A) with long course
chemoradiotherapy followed by surgery. In arm A adjuvant chemotherapy is allowed according
to the local protocol of the institution. In both groups the rectal tumour will be removed
by TME surgery or more extensive surgery if required because of tumour extent.
Inclusion Criteria:
Primary tumour characteristics:
1. Histological proof of newly diagnosed primary adenocarcinoma of the rectum
2. Locally advanced tumour fulfilling at least one of the following criteria on pelvic
MRI indicating high risk of failing locally and/or systemically (T4a, i.e. overgrowth
to an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum,
pelvic floor or side wall (according to TNM version 5), cT4b, i.e. peritoneal
involvement, extramural vascular invasion (EMVI+). N2, i.e. four or more lymph nodes
in the mesorectum showing morphological signs on MRI indicating metastatic disease.
Positive MRF, i.e. tumor or lymph node < 1 mm from the mesorectal fascia. Enlarged
lateral nodes, > 1 cm (lat LN+)
Exclusion Criteria:
1. Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve
roots indicating that surgery will never be possible even if substantial tumour
down-sizing is seen
2. Presence of metastatic disease or recurrent rectal tumour
3. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal
Cancer (HNPCC), active Crohn¡¦s disease or active ulcerative Colitis
4. Concomitant malignancies, except for adequately treated basocellular carcinoma of the
skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must
be disease-free for at least 5 years
5. Known DPD deficiency
6. Any contraindications to MRI (e.g. patients with pacemakers)
7. Medical or psychiatric conditions that compromise the patient's ability to give
informed consent
8. Concurrent uncontrolled medical conditions
9. Any investigational treatment for rectal cancer within the past month
10. Pregnancy or breast feeding
11. Patients with known malabsorption syndromes or a lack of physical integrity of the
upper gastrointestinal tract
12. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure,
symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial
fibrillation, even if controlled with medication) or myocardial infarction within the
past 12 months
13. Patients with symptoms or history of peripheral neuropathy
We found this trial at
2
sites
Saint Louis, Missouri
Principal Investigator: P Parikh
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