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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Apr 2018 → 30 Jul 2025

Decision date (initial)

2024-10-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-517928-19-00

EudraCT number

2017-003057-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

estimate the effect of radiochemotherapy
followed by consolidation chemotherapy in locally advanced rectal cancer

Conditions and MedDRA coding

Male and female patients with histologically confirmed diagnosis of rectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Male and female patients with histologically confirmed diagnosis of rectalcancer localized 0 – 12 cm from the anocutaneous line as measured byrigid rectoscopy (i.e. lower and middle third of the rectum) Any MRI staged cT3 tumor or any cT1 cN+ or cT2 cN+ with nodal stagingaccording to “SOP MRI” Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magneticresonance imaging (MRI) of the pelvis is the mandatory local stagingprocedure. Cross-sectional imaging of the abdomen and chest to exclude distantmetastases. Aged at least 18 years. No upper age limit. WHO/ECOG Performance Status ≤ 1 Adequate hematological, hepatic, renal and metabolic function parameters:o Leukocytes ≥ 3.000/mm^3o ANC ≥ 2.000/mm^3o Platelets ≥ 100.000/mm^3 Hb > 9 g/dlo Serum creatinine ≤ 1.5 x upper limit of normalo Creatinin-Clearance ≥ 30 ml / mino Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit ofnormalo Informed consent of the patient Informed consent of the patient

Exclusion criteria 1

1. Lower border of the tumor localised more than 12 cm from theanocutaneous line as measured by rigid rectoscopy cT4 tumors Positive lateral pelvic lymph nodes (s. SOP MRI) Distant metastases (to be excluded by CT scan of the thorax andabdomen) Preexisting fecal incontince for solid stool Preexisting peripheral sensory neuropathy with functional impairment Preexisting myelosuppression refleted by a neutrophil count < 2.000/mm^3and/or platelets < 100.000/mm^3 Severe impairment of kidney function with a Creatinin Clearance < 30ml/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 within6 months after the end of treatment. Subject (male or female) is not willing to use highly effective methods ofcontraception according to the “Clinical trial fertility group”recommendations(http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) during treatment and for 6 months (male or female) after the end oftreatment (adequate: combined hormonal contraception associated withinhibition of ovulation, progestogen-only hormonal contraceptionassociated with inhibition of ovulation, intrauterine device, intrauterinehormone-releasoing system, bilateral tubal occlusion, vasectomizedpartner1, sexual abstinence2). On-treatment participation in an interventional clinical study in the period 30days 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 uncontrolledcardiac 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 stage0-1), if the patient is continuously disease-free Known allergic reactions on study medication Known dihydropyrimidine dehydrogenase deficiency Medication inhibitors of the dihydropyrimidine dehydrogenase, such asBrivudin, Sorivudin and its analogues. Pernicious anemia or other anemias caused by Vitamin B-12 deficiency. Psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule(these conditions should be discussed with the patient before registration inthe trial). Additionally for hyperthermia cardiac pacemakers and metal implants in theproximity of the pelvis constitute a criterion for exclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary objective of the present study is to estimate the clinical complete response rate after anintensified radiochemotherapy regimen in locally advanced rectal cancer. This clinical completeresponse determined in this study will be the basis for a consecutive study using the sameradiochemotherapy regimen with 2-year local control as endpoint.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

PM

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

PM

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications