Translational Validation Study to Examine KFO179-1 Biomarker Scores for the Prediction and Prognosis of Advanced Primary Resectable Rectal Cancer Stages UICC-II-IV, With a 5-Fluorouracil-based Standard Radiochemotherapy Followed by Total Mesorectal Excision. (TransValid-A)

University Medical Center Goettingen

Status: Active, not recruiting

Conditions: Locally Advanced Rectal Cancer

Treatments: Other: Translational Research and multimodal treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT03034473

TransValid-KFO179/GRCSG-A

UTN U1111-1131-9971 (Registry Identifier)

DRKS00003659 (Registry Identifier)

Details and patient eligibility

About

The objective of the TransValid-KFO179/GRCSG-Trial-A is the validation of potential biomarkers. These are predictive (Prediction of probability of response to a certain therapy) / prognostic (predicting long-term outcome) microarray-based gene expression signatures and immunohistochemically evaluated biomarkers. The evaluation was done within the KFO179 (www.kfo179.de) - the validation is implemented in this trial.

Therefore tumor material of patients undergoing standard radiochemotherapy will be analyzed from pretreatment biopsies an residual tissue from the resection specimen after surgery. This validation and the biomaterial asservation will be incorporated into clinical routine in all participating centers as a model for the treatment of solid tumors. The obtained biomarkers with a predictive and prognostic power will be used to develop an algorithm to predict patients at high risk of local and distant cancer recurrence.

Full description

The objective of the TransValid-KFO179/GRCSG-Trial-A is to validate the predictive/prognostic microarray-based gene expression signatures and single gene biomarkers (including 5-Fluorouracil (FU) metabolism, apoptosis, Kirsten Rat Sarcoma (KRAS), CpGCpG island methylation phenotype (CIMP) and TGF-beta pathway), which have been established in patients treated with standard 5-FU based RCT in the GRCSG trials (e.g. the CAO/ARO/AIO-94-, CAO/ARO/AIO-04-phase III trials). This validation will be incorporated into clinical routine in all participating centers as a model for the treatment of solid tumors. If the KFO179 biomarkers are predictive at a satisfactory level in the validation set, we will propose a prediction algorithm to stratify the patient population into a "high"-risk and "low"-risk population to develop local and distant cancer recurrence.

Enrollment: 200 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 18 to 85 years, inclusive
• Histologically confirmed advanced primary rectal cancer localized up to 12 cm above the anocutaneous line (determined with a rigid rectoscope), classified as T3/T4 or N+ carcinomas or with evidence for synchronous, but resectable distant metastases (liver or lung metastases)
• No specific tumor treatment except colostomy due to tumor stenosis with ileus
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) status ≤2
• Adequate bone marrow function (WBC >3.0x10^9/L, neutrophils >1.5x10^9/L, thrombocytes >100x10^9/L, hemoglobin ≥10 g/dl)
• Adequate liver function (bilirubin ≤2.0 mg/dl, SGOT, SGPT, AP, gamma-GT < three point five fold of upper level of normal range
• serum creatinine < 1.5 mg/dl
• Written and signed informed consent indicating the understanding of the investigational nature and the study protocol.

Exclusion criteria

• Pregnant or lactating women

• Men and women unwilling or unable to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment

• Prolonged drug, medication or alcohol abuse

• Previous chemotherapy (up to 2 years before diagnosis of rectal cancer)

• Previous radiotherapy to the pelvic area

• Simultaneous therapy with other anti-cancer drugs

• Participation in a clinical trial in the period 30 days prior to inclusion

• Patients (man and woman) who are not able or willing to accept treatment and follow-up care according to trial protocol

• Patients (man and woman) with uncontrolled, serious physical or mental diseases, e.g.: instable cardiac disease in spite of medical treatment, myocardial infarction during the last 3 months prior to start of trial participation

  • neurological or psychiatric dysfunction including dementia or seizure disorder
  • Disseminated infection or sepsis
  • Disseminated intravascular coagulopathy
  • Symptomatic neuropathy (NCI CTC ≥2)

• Patients with secondary malignancies except basal cell carcinoma of the skin or carcinoma in situ of the cervix, which have been successfully treated. (The inclusion of patients with other tumors that were successfully treated and no recurrence within the last 3-5 years should be discussed before registration in the trial)

• Chronic diarrhea (>grade 1 according NCI CTCAE)

• Allergic reaction to platin-derivates or study medication

• Simultaneous treatment with sorivudine and analogous

• Known Dihydropyrimidine dehydrogenase deficiency

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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200 participants in 1 patient group

Blood and tissue samples during therapy

Other group

Description:

Collection of blood and tissue samples during preoperative multimodal treatment (Radiochemotherapy (RCTx) followed by total mesorectal excision (TME) and Chemotherapy (CT)) in rectal cancer.

Treatment:

Other: Translational Research and multimodal treatment