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Status unknownNCT03561142CAO/ARO/AIO-16Updated Jun 19, 2018

Organ Preservation in Locally Advanced Rectal Cancer by Radiochemotherapy Followed by Consolidation Chemotherapy.

A Phase 2 interventional study of Radiotherapy and Chemotherapy in Rectal Cancer, Rectal Neoplasms and Rectal Cancer Stage II, sponsored by University Hospital Tuebingen. Status unknown at 4 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-06-19.

Sponsored by University Hospital Tuebingen · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Apr 2018), so the status shown — last known as Recruiting — may be out of date.
Phase
Phase 2
Study type
Interventional
Enrollment
94
Allocation
Not applicable
Ages
18 Years and older
Sex
All
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Study 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.

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Conditions studied

  • Rectal Cancer
  • Rectal Neoplasms
  • Rectal Cancer Stage II
  • Rectal Cancer Stage III

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03

In context

Rectal Neoplasms

1,762 studies on the registry are indexed under Rectal Neoplasms; 518 are open to participants now.

This study's planned enrollment of 94 is above the median of 65 across 1,298 interventional studies indexed under Rectal Neoplasms.

Browse Rectal Neoplasms studies →

Lead sponsor

University Hospital Tuebingen is the lead sponsor of 476 studies on the registry; 104 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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.
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Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
94 participants (estimated)

Study arms

  • Experimental
    Radiochemotherapy -> chemotherapy.

    Radiochemotherapy followed by consolidation chemotherapy. Deep regional hyperthermia can additionally be performed at the centers in Tübingen and Erlangen.

    Radiation: Radiotherapy · Drug: Chemotherapy · Other: Deep regional hyperthermia

Interventions

  • RadiationRadiotherapy

    Radiotherapy: 28 x 1.8 Gy (total: 50.4 Gy), 5 fractions per week on day 1- 38

  • DrugChemotherapy

    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

    Also known as: all brands of the used drugs are allowed

  • OtherDeep 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.

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What researchers measure

Primary outcomes

  1. Clinical complete response rate

    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

    Time frame: Day 106 after the start of treatment

Secondary outcomes

  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

    Possible scores range from 0 (perfect continence) to 24 (complete incontinence)

    Time frame: 4 years

  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

07

Study locations

1 of 4 sites recruiting
  • University Hospital Erlangen
    Erlangen, Germany
    • Oliver Ott, Prof. · Contact
    Not yet recruiting
  • University Hospital Frankfurt
    Frankfurt, Germany
    • Claus Rödel, Prof. · Contact
    Not yet recruiting
  • University Hospital Tübingen
    Tübingen, Germany
    • Cihan Gani, Dr. · Contact
    Recruiting
  • University Hospital Würzburg
    Würzburg, Germany
    • Bülent Polat, Dr. · Contact
    Not yet recruiting
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References and documents

Publications

  • Gani C, Bonomo P, Zwirner K, Schroeder C, Menegakis A, Rodel C, Zips D. Organ preservation in rectal cancer - Challenges and future strategies. Clin Transl Radiat Oncol. 2017 Mar 23;3:9-15. doi: 10.1016/j.ctro.2017.02.002. eCollection 2017 Apr. PubMed 29658007 ↗
  • Schroeder C, Gani C, Lamprecht U, von Weyhern CH, Weinmann M, Bamberg M, Berger B. Pathological complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with regional hyperthermia for locally advanced rectal cancer compared with radiochemotherapy alone. Int J Hyperthermia. 2012;28(8):707-14. doi: 10.3109/02656736.2012.722263. Epub 2012 Sep 24. PubMed 23006132 ↗
  • Rodel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Strobel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. doi: 10.1016/S1470-2045(15)00159-X. Epub 2015 Jul 15. PubMed 26189067 ↗

Individual participant data

Plan to share: Undecided

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03561142
Lead sponsor
University Hospital Tuebingen
Responsible party
Sponsor
First posted
Jun 19, 2018
Start date
Jun 15, 2018 (estimated)
Primary completion
Apr 16, 2020 (estimated)
Completion
Apr 16, 2024 (estimated)
Last update
Jun 19, 2018

Study contacts

Cihan Gani, Dr.
Contact
cihan.gani@med.uni-tuebingen.de
+4970712982165
Daniel Zips, Prof.
Contact
daniel.zips@med.uni-tuebingen.de
+4970712982165
Cihan Gani, Dr.
principal investigator · University Hospital Tübingen

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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