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Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy. (CAO/ARO/AIO-16)

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ClinicalTrials.gov Identifier: NCT03561142
Recruitment Status : Recruiting
First Posted : June 19, 2018
Last Update Posted : June 19, 2018
Information provided by (Responsible Party):
University Hospital Tuebingen

Brief Summary:
There is a growing body of evidence that surgery and associated morbidities can be omitted without compromising oncological safety in selected patients who have achieved a clinical complete response after radiochemotherapy. However with standard neoadjuvant treatment regimens the pathological complete response rate lies in the range between 10%-20%, the number of patients qualifying for non-operative management is even lower since the sensitivity of currently available diagnostic measures for predicting the pathological complete response hardly surpasses 50%-60%.The hereby proposed phase II trial CAO/ARO/AIO-16 aims at finding novel and innovative aspects of rectal cancer treatment. According to recently published data the radiochemotherapy regime in the present study with consolidating chemotherapy and delayed assessment of response has the potential to achieve pathological complete rates of approximately 40%. A standardized re-evaluation after consolidating chemotherapy will select patients who are candidates for organ-preservation. These patients will not undergo radical surgery and will instead be follow-up closely for tumor regrowth.

Condition or disease Intervention/treatment Phase
Rectal Cancer Rectal Neoplasms Rectal Cancer Stage II Rectal Cancer Stage III Radiation: Radiotherapy Drug: Chemotherapy Other: Deep regional hyperthermia Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Patients will undergo different treatments based on response achieved after radiochemotherapy.

  1. Clinical Complete Response: Omission of surgery and follow-up
  2. Near clinical complete response: Reevaluation in three months
  3. Poor / no response: Surgery
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy. A Prospective Phase II Pilot Trial of the German Rectal Cancer Study Group
Estimated Study Start Date : June 15, 2018
Estimated Primary Completion Date : April 16, 2020
Estimated Study Completion Date : April 16, 2024

Arm Intervention/treatment
Experimental: Radiochemotherapy -> chemotherapy.
Radiochemotherapy followed by consolidation chemotherapy. Deep regional hyperthermia can additionally be performed at the centers in Tübingen and Erlangen.
Radiation: Radiotherapy
Radiotherapy: 28 x 1.8 Gy (total: 50.4 Gy), 5 fractions per week on day 1- 38

Drug: Chemotherapy
chemoradiotherapy is started according to the following schedule: 5-FU: 250 mg/sqm per day, iv, on day 1-14, day 22-35; Oxaliplatin: 50 mg/sqm, day 1, 8, 22, and 29. After a break of two and a half weeks, patients receive three chemotherapy cycles, starting on day 57, 71 and 85, consisting of: Folinic acid: 400 mg/sqm, 2h-iv; Oxaliplatin: 100 mg/sqm, 2h-iv; 5-FU: 2400 mg/sqm, 46h-iv
Other Name: all brands of the used drugs are allowed

Other: Deep regional hyperthermia

Deep regional hyperthermia to the pelvis, total time 90 min, target temperature 41-42°C. Twice weekly, up to a total of 10 sessions within d1 and d38.

Deep regional hyperthermia is offered at the centers in Tübingen and Erlangen.

Primary Outcome Measures :
  1. Clinical complete response rate [ Time Frame: Day 106 after the start of treatment ]

    Response to treatment is assessed on day 106 after the start of radiochemotherapy.

    A clinical complete response is defined by standardized findings in rectoscopy, MRI and digital rectal examination

Secondary Outcome Measures :
  1. Local regrowth rate [ Time Frame: 4 years ]
  2. Safety of the treatment (toxicity assessment according to NCI CTCAE Version 4.0) [ Time Frame: 4 years ]
  3. Fecal incontinence according to Wexner-Vaizey Score [ Time Frame: 4 years ]
    Possible scores range from 0 (perfect continence) to 24 (complete incontinence)

  4. Quality of life according to EORTC Quality of Life questionnaire - C30 [ Time Frame: 4 years ]
  5. Quality of life according to EORTC Quality of Life questionnaire - CR29 [ Time Frame: 4 years ]
  6. Frequency of Low anterior resection syndrome (LARS-scale) [ Time Frame: 4 years ]
  7. Surgical morbidity in patients undergoing surgery [ Time Frame: up to 30 days after surgery ]
  8. Surgical complications in patients undergoing surgery [ Time Frame: up to 30 days after surgery ]
  9. Pathological staging, tumor downstaging (assessed by ypTNM findings in relation to initial cTNM staging), tumor regression grading according to Dworak in patients undergoing surgery [ Time Frame: Day 123 after the start of treatment ]
  10. R0 resection rate, rate of circumferential resection margin negativity (> 1mm) in patients undergoing surgery [ Time Frame: Day 123 after the start of treatment ]
  11. Rate of sphincter-sparing surgery in patients undergoing surgery [ Time Frame: Day 123 after the start of treatment ]
  12. Relapse-free survival (local / distant / overall) [ Time Frame: 4 years ]
  13. Overall survival [ Time Frame: 4 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male and female patients with histologically confirmed diagnosis of rectal cancer localized 0 - 12 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower and middle third of the rectum)
  • Any MRI staged cT3 tumor or any cT1 cN+ or cT2 cN+ with nodal staging according to "SOP MRI"
  • Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
  • Cross-sectional imaging of the abdomen and chest to exclude distant metastases.
  • Aged at least 18 years. No upper age limit.
  • WHO/ECOG Performance Status ≤ 1
  • Adequate hematological, hepatic, renal and metabolic function parameters
  • Informed consent of the patient

Exclusion Criteria:

  • Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy
  • cT4 tumors
  • Positive lateral pelvic lymph nodes
  • Distant metastases (to be excluded by CT scan of the thorax and abdomen)
  • Preexisting fecal incontinence for solid stool
  • Preexisting peripheral sensory neuropathy with functional impairment
  • Preexisting myelosuppression reflected by a neutrophil count < 2.000/mm^3 and/or platelets < 100.000/mm^3
  • Severe impairment of kidney function with a Creatinin Clearance < 30 ml/min)
  • Prior antineoplastic therapy for rectal cancer
  • Prior radiotherapy of the pelvic region
  • Major surgery within the last 4 weeks prior to inclusion
  • Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
  • Subject (male or female) is not willing to use highly effective methods of contraception according to the "Clinical trial fertility group"
  • On-treatment participation in an interventional clinical study in the period 30 days prior to inclusion
  • Previous or current drug abuse
  • Other concomitant antineoplastic therapy
  • Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder, severe liver function disorders
  • WHO/ECOG Performance Status > 1
  • Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment.
  • Chronic diarrhea (> grade 1 according NCI CTCAE) Prior or concurrent malignancy ≤ 3 years prior to enrolment in study (Exception: non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1), if the patient is continuously disease-free
  • Known allergic reactions on study medication
  • Known dihydropyrimidine dehydrogenase deficiency
  • Medication inhibitors of the dihydropyrimidine dehydrogenase, such as Brivudin, Sorivudin and its analogues.
  • Pernicious anemia or other anemias caused by Vitamin B-12 deficiency.
  • Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial).
  • Additionally for hyperthermia cardiac pacemakers and metal implants in the proximity of the pelvis constitute a criterion for exclusion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03561142

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Contact: Cihan Gani, Dr. +4970712982165 cihan.gani@med.uni-tuebingen.de
Contact: Daniel Zips, Prof. +4970712982165 daniel.zips@med.uni-tuebingen.de

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University Hospital Erlangen Not yet recruiting
Erlangen, Germany
Contact: Oliver Ott, Prof.         
University Hospital Frankfurt Not yet recruiting
Frankfurt, Germany
Contact: Claus Rödel, Prof.         
University Hospital Tübingen Recruiting
Tübingen, Germany
Contact: Cihan Gani, Dr.         
University Hospital Würzburg Not yet recruiting
Würzburg, Germany
Contact: Bülent Polat, Dr.         
Sponsors and Collaborators
University Hospital Tuebingen
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Principal Investigator: Cihan Gani, Dr. University Hospital Tübingen
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Responsible Party: University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT03561142    
Other Study ID Numbers: CAOAROAIO16
First Posted: June 19, 2018    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases