Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation. The RAPIDO Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University Medical Centre Groningen
Sponsor:
Collaborators:
Karolinska University Hospital
Leiden University Medical Center
Uppsala University Hospital
Dutch Cancer Society
Information provided by (Responsible Party):
B. van Etten, MD, PhD, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01558921
First received: March 18, 2012
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

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 ivestigators 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.


Condition Intervention Phase
Rectal Cancer
Other: M1 scheme
Other: standard long course chemoradiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • disease-free survival [ Time Frame: 3 year ] [ Designated as safety issue: No ]
    Disease-free survival will be computed as the time between randomization and either local or distant relapse or death caused by the rectal carcinoma whichever comes first. In case of nonrectal cancer related death patients will be censored at date of death. In case of a second primary tumour patients will be censored at the date of diagnosis of the second primary tumour. Patients lost to follow-up will be censored the last date of patient visit.Survival curves for disease-free survival after 3 years of follow-up will be constructed using the method of Kaplan and Meier.


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 year ] [ Designated as safety issue: No ]
  • CRM negative (margin > 1 mm) rate [ Time Frame: within 30 days ] [ Designated as safety issue: Yes ]
  • Pathological complete response (pCR) rate [ Time Frame: within 30 days ] [ Designated as safety issue: Yes ]
  • Short and long-term toxicity [ Time Frame: 3 year ] [ Designated as safety issue: Yes ]
  • Surgical complications [ Time Frame: 3 year ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: 3 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 885
Study Start Date: June 2011
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B: 5x5Gy -> CAPOX -> surgery
experimental group (arm B) M1 scheme
Other: M1 scheme
short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin) and surgery
Active Comparator: A: 5 weeks chemoradiation -> surgery
control group (arm A) standard long course chemoradiotherapy
Other: standard long course chemoradiotherapy
long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy is allowed in the control group.

Detailed Description:

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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. Four or more nodes, whether enlarged or not, with a rounded, homogeneous appearance is thus not sufficient. Positive MRF (previously named CRM), 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01558921

Contacts
Contact: B. van Etten, Md, PhD +31-50-3612317 b.van.etten@umcg.nl
Contact: A.G.H. Roodvoets, MSc +31-71-526 3500 datacenter@lumc.nl

  Show 58 Study Locations
Sponsors and Collaborators
University Medical Centre Groningen
Karolinska University Hospital
Leiden University Medical Center
Uppsala University Hospital
Dutch Cancer Society
Investigators
Principal Investigator: B. van Etten, Md, PhD University Medical Center Groningen, Department of Surgery, Groningen, The Netherlands
Principal Investigator: B. Glimelius, MD, PhD Akademiska sjukhuset, Department of Oncology, Uppsala, Sweden
Principal Investigator: G. A. Hospers, MD, PhD University medical Center Groningen, Department of Medical Oncology, Groningen, The Netherlands
Principal Investigator: L. Påhlman, MD, PhD Akademiska sjukhuset, Department of Surgery, Uppsala, Sweden
Principal Investigator: C. J. van de Velde, Md, PhD Leiden University Medical Center, Department of Surgery, Leiden, The Netherlands
Principal Investigator: C.A.M. Marijnen Leids Universitair Medisch Centrum
  More Information

Additional Information:
No publications provided by University Medical Centre Groningen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: B. van Etten, MD, PhD, Dr. B. van Etten, surgical oncologist, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01558921     History of Changes
Other Study ID Numbers: NL36315.042.11, 2010-023957-12
Study First Received: March 18, 2012
Last Updated: September 4, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
rectal cancer
radiotherapy
chemotherapy
5x5
capecitbine
oxaliplatin

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 18, 2014