Trial document



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  DRKS00004186

Trial Description

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Title

Translational Validation Trial-B (add-on phase I/II study to the Clinical Research Unit (Klinische Forschergruppe) KFO179-2: Preoperative radiochemotherapy (RCT) combined with 5-fluorouracil (5-FU) and oxaliplatin followed by 3 cycles of FOLFOX chemotherapy (5-FU+folinic acid+oxaliplatin) and total mesorectal excision (TME-surgery) in advanced rectal cancer (clinically staged as UICC stages II, III or IV) accompanied by molecular and cell biological (translational) analysis.

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Trial Acronym

TransValid-KFO179/GRCSG-B-Trial

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URL of the Trial

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Brief Summary in Lay Language

Within the TransValid-KFO179/GRCSG-Trial-B the treatment modalities are modified by placing the chemotherapy part before surgery. The trial tests, if modification of the treatment sequences radiochemotherapy followed by 3 cycles of FOLFOX (5-Fluorouracil, oxaliplatin, folinic acid) and surgery with total mesorectal excision can improve the response rate for rectal cancer and reduce side-effects of chemotherapy. This approach avoids the problem of major compliance problems associated with post-operative adjuvant chemotherapy and is combined with biomolecular analysis of biomaterials.

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Brief Summary in Scientific Language

TransValid-KFO179/GRCSG-Trial-B study tests the modification of the sequence of the three treatment modalities by placing the chemotherapy part before TME surgery.
All patients will receive preoperative RCT (total dose: 50.4 Gy, 28 fractions with a single dose of 1.8 Gy) combined with 5-FU (250 mg/m2 civ infusion on d1-d14 and d22-d35) and oxaliplatin (50 mg/m2 2h iv on d1, d8, d22 and d35). Three weeks after completion of RCT, patients will receive 3 applications of a shortened FOLFOX regimen [(400 mg FA/m2, 2-h civ, d 1; 100 mg oxaliplatin/m2 2-h civ in 500 ml Glucose 5%, d 1; 2400 mg 5-FU/m2 as 46-h civ infusion) on d1+d15+d30] as recently used within the CAO/AIO/ARO-04 trial (in adjuvant postoperative intent). TME-surgery will be performed 3-4 weeks after completion of RCT+CTx.
This innovative preoperative sequence of RCT followed by chemotherapy and TME-surgery is postulated to be beneficial according to response kinetics considerations and by maintaining an enhanced locoregional treatment in first place. This approach avoids the problem of major compliance problems associated with post-operative adjuvant chemotherapy.

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Organizational Data

  •   DRKS00004186
  •   2012/10/26
  •   [---]*
  •   yes
  •   Approved
  •   23/10/11, Ethik-Kommission der Medizinischen Fakultät der Georg-August-Universität Göttingen
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Secondary IDs

  •   U1111-1132-0235 
  •   2011-004228-37 
  •   4038135 
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Health Condition or Problem studied

  •   C20 -  Malignant neoplasm of rectum
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Interventions/Observational Groups

  •   - All patients receive preoperative RCT (radiochemotherapy) (total dose: 50.4 Gy, 28 fractions with a single dose of 1.8 Gy, applied as three-dimensional conformal irradiation by a three-field box technique combined with 5-FU (5-Fluorouracil) (250 mg/m2/d civ infusion on d1-d14 and d22-d35) and oxaliplatin (50 mg/m2 2h iv on d1, d8, d22 and d35 in 500 ml glucose 5%).
    - Three weeks after completion of RCT, patients receive 3 applications of a shortened FOLFOX regimen [(400 mg FA (folinic acid) (/m2, 2-h civ, d 1; 100 mg oxaliplatin/m2 2-h civ in 500 ml Glucose 5%, d 1; 2400 mg 5-FU/m2 as 46-h civ infusion) on d1+d15+d30] as recently used within the CAO/AIO/ARO-04 trial.
    - TME-surgery is performed 3-4 weeks after completion of RCT+CTx.
    - The follow-up procedures take place according to national guidelines (S3-Guideline, Dt. Krebsgesellschaft.
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   N/A
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Primary Outcome

Toxicity and histopathologically confirmed complete remission (pCR) will be compared exploratively to the TransValid-KFO179/ GRCSG-A-Trial.

The aim of this study is to establish the feasibility and to receive first data on the efficacy of an innovative sequential combination of established pre-operative intensified RCT (5-FU+Oxaliplatin) with consecutively intensive but shortened preoperative FOLFOX-chemotherapy (5-FU+Oxaliplatin) followed by TME-surgery.

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Secondary Outcome

The results will be used in planned studies of the GRCSG (e.g. the CAO/AIO/ ARO-12 Trial, a randomized multicentric phase IIb trial).

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2013/04/05
  •   50
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   80   Years
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Additional Inclusion Criteria

- Males and females with histologically confirmed resectable advanced primary rectal cancer of the lower thirds of the rectum (localized within 0 to 12 cm above the anocutaneous verge as measured by rigid rectoscopy), clinically (c) classified as cT3/cT4 or cN+ carcinomas or with evidence for synchronous, but resectable distant metastases (liver metastases, pulmonary metastases)
- Aged 18 to 80 years, inclusive
- WHO/ECOG status ≤2
- Life expectancy >12weeks
- Adequate bone marrow function: WBC >3.0x109/L, neutrophils >1.5x109/L, thrombocytes >100x109/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
- Creatinine clearance > 50ml/min, serum creatinine <1.5 mg/dl
- Written and signed informed consent of competent patient

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Exclusion Criteria

1. Prior or concurrent malignancy except non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is successfully treated. Patients with other tumors that have been successfully treated and have not reappeared during the last 3-5 years, may be included at the principal investigator’s discretion
2. Simultaneous therapy with other anti-cancer drugs
3. Major surgery at the pelvic region 2-3 weeks prior to inclusion
4. Previous chemotherapy (last 2 years before diagnosis of rectal cancer)
5. Chronic colonic diseases
6. Chronic diarrhea (>grade 1 according NCI CTCAE)
7. Allergic reaction to platin derivates or study medication
8. Known Dehydropyrimidindehydrogenase (DPD) deficiency
9. Symptomatic neuropathia (NCI CTC >1)
10. Concomitant treatment with sorivudin and analogous
11. Disseminated infection or sepsis
12. Disseminated intravascular coagulopathy
13. 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
14. 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.
15. Patients (man and woman) who are not able or willing to accept treatment and follow-up care according to trial protocol.
16. Participation in an AMG-clinical trial in the period 30 days prior to inclusion
17. Current drug abuse
18. neurological or psychiatric dysfunction including dementia or seizure disorder

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Addresses

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    • Universitätsmedizin Göttingen Georg-August-Universität
    • Robert-Koch-Straße 40
    • 37075  Göttingen
    • Germany
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    • Universitätsmedizin GöttingenGeorg-August-UniversitätKlinik für Allgemein-, Viszeral- und Kinderchirurgie
    • Mr.  Prof. Dr.  Torsten   Liersch 
    • Robert-Koch-Straße 40
    • 37075  Göttingen
    • Germany
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    • Universitätsmedizin Göttingen Georg-August-Universität
    • Ms.  MA  Johanna  Kreutzer 
    • Robert-Koch-Straße 40
    • 37075  Göttingen
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft (DFG)
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.