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

NCT ID: NCT03561142

Last Updated: 2018-06-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-15
• Study Completion Date: 2024-04-16

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiochemotherapy -> chemotherapy.

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

Group Type: EXPERIMENTAL

Radiotherapy

Intervention Type: RADIATION

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

Chemotherapy

Intervention Type: 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

Deep regional hyperthermia

Intervention Type: 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.

Interventions

Radiotherapy

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

Intervention Type: RADIATION

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

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

all brands of the used drugs are allowed

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cihan Gani, Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tübingen

Locations

University Hospital Erlangen

Erlangen, , Germany

Site Status: NOT_YET_RECRUITING

University Hospital Frankfurt

Frankfurt, , Germany

Site Status: NOT_YET_RECRUITING

University Hospital Tübingen

Tübingen, , Germany

Site Status: RECRUITING

University Hospital Würzburg

Würzburg, , Germany

Site Status: NOT_YET_RECRUITING

Countries

Germany

Central Contacts

Cihan Gani, Dr.

Role: CONTACT

cihan.gani@med.uni-tuebingen.de

+4970712982165

Daniel Zips, Prof.

Role: CONTACT

daniel.zips@med.uni-tuebingen.de

+4970712982165

Facility Contacts

Oliver Ott, Prof.

Role: primary

Claus Rödel, Prof.

Role: primary

Cihan Gani, Dr.

Role: primary

Bülent Polat, Dr.

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 29658007 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23006132 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26189067 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40347958 (View on PubMed)

Other Identifiers

CAOAROAIO16

Identifier Type: -

Identifier Source: org_study_id