Trial document



drksid header

  DRKS00004186

Trial Description

start of 1:1-Block title

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.

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

TransValid-KFO179/GRCSG-B-Trial

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

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.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

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.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00004186
  •   2012/10/26
  •   [---]*
  •   yes
  •   Approved
  •   23/10/11, Ethik-Kommission der Medizinischen Fakultät der Georg-August-Universität Göttingen
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1132-0235 
  •   2011-004228-37 
  •   4038135 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   C20 -  Malignant neoplasm of rectum
end of 1:N-Block indications
start of 1:N-Block interventions

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.
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

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.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

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).

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2013/04/05
  •   50
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   80   Years
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

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

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

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

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsmedizin Göttingen Georg-August-Universität
    • Robert-Koch-Straße 40
    • 37075  Göttingen
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Universitätsmedizin GöttingenGeorg-August-UniversitätKlinik für Allgemein-, Viszeral- und Kinderchirurgie
    • Mr.  Prof. Dr.  Torsten   Liersch 
    • Robert-Koch-Straße 40
    • 37075  Göttingen
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universitätsmedizin Göttingen Georg-August-Universität
    • Ms.  MA  Johanna  Kreutzer 
    • Robert-Koch-Straße 40
    • 37075  Göttingen
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Deutsche Forschungsgemeinschaft (DFG)
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting complete, follow-up continuing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.