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

NCT03561142 | Unknown Phase 2 DMC

• 1 other identifier: CAOAROAIO16
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 4

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.

Conditions

Rectal Cancer; Rectal Neoplasms; Rectal Cancer Stage II; Rectal Cancer Stage III

Outcome Measures

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

  Day 106 after the start of treatment

Secondary Outcomes (13)

• Local regrowth rate

  4 years

• Safety of the treatment (toxicity assessment according to NCI CTCAE Version 4.0)

  4 years

• Fecal incontinence according to Wexner-Vaizey Score

  4 years

• Quality of life according to EORTC Quality of Life questionnaire - C30

  4 years

• Quality of life according to EORTC Quality of Life questionnaire - CR29

  4 years

Study Arms (1)

Radiochemotherapy -> chemotherapy.

EXPERIMENTAL

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

Radiotherapy RADIATION

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

Radiochemotherapy -> chemotherapy.

Chemotherapy DRUG

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

Radiochemotherapy -> chemotherapy.

Deep regional hyperthermia OTHER

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.

Radiochemotherapy -> chemotherapy.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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"
• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (4)

University Hospital Erlangen

Erlangen, Germany

NOT YET RECRUITING

University Hospital Frankfurt

Frankfurt, Germany

NOT YET RECRUITING

University Hospital Tübingen

Tübingen, Germany

RECRUITING

University Hospital Würzburg

Würzburg, Germany

NOT YET RECRUITING

Related Publications (4)

• 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.

  PMID: 29658007 BACKGROUND

• 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.

  PMID: 23006132 BACKGROUND

• 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.

  PMID: 26189067 BACKGROUND

• Gani C, Fokas E, Polat B, Ott OJ, Diefenhardt M, Konigsrainer A, Boke S, Kirschniak A, Bachmann R, Wichmann D, Bitzer M, Clasen S, Grosse U, Hoffmann R, Gotz M, Hofheinz RD, Germer E, Germer CT, Fietkau R, Martus P, Zips D, Rodel C. Organ preservation after total neoadjuvant therapy for locally advanced rectal cancer (CAO/ARO/AIO-16): an open-label, multicentre, single-arm, phase 2 trial. Lancet Gastroenterol Hepatol. 2025 Jun;10(6):562-572. doi: 10.1016/S2468-1253(25)00049-4.

  PMID: 40347958 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Cihan Gani, Dr.

  University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cihan Gani, Dr.

CONTACT

+4970712982165; cihan.gani@med.uni-tuebingen.de

Daniel Zips, Prof.

CONTACT

+4970712982165; daniel.zips@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: June 19, 2018
• Study Start: June 15, 2018
• Primary Completion: April 16, 2020
• Study Completion: April 16, 2024
• Last Updated: June 19, 2018

Record last verified: 2018-04

Locations

DE (4)