Letzte Aktualisierung: 05.04.2023

Gallenblasenkarzinom

GAIN - AIO-HEP-0118/ass

Aktive Studien

Studieninformationen

Neoadjuvant Chemotherapy With Gemcitabine Plus Cisplatin Followed by Radical Liver Resection Versus Immediate Radical Liver Resection Alone With or Without Adjuvant Chemotherapy in Incidentally Detected Gallbladder Carcinoma After Simple Cholecystectomy or in Front of Radical Resection of BTC (GAIN)

Behandlungszentren im CIO

Bonn


Ziele

Primäres Prüfziel

Sekundäre Prüfziele für die Behandlungsarme:


Design

Phase

Phase III

Zentren

Multizentrisch

Datenerhebung

Randomisiert

Interventionsgruppen

Zweiarmig

Verblindung

Open Label

Erkrankung

Diagnose

Gallenblasenkarzinom

Diagnosenbeschreibung

Incidental Gallbladder CarcinomaBiliary Tract Cancer

Mutation

Stadium

Patienten

Alter

Einschlusskriterien

Histologically/cytologically confirmed incidental gallbladder carcinoma (IGBC) (T2-3 after Cholecystectomy) or Biliary tract cancer (BTC) (intrahepatic, hilar or distal Cholangiocarcinoma (CCA)) scheduled for complete resection (mixed tumor entities with hepatocellular carcinoma are excluded). No prior partial or complete tumor resection for BTC (intrahepatic, hilar or distal CCA), for IGBC (T2-3) prior Cholecystectomy is allowed. Exclusion of distant metastases by CT or MRI of abdomen, pelvis, and thorax, bone scan or MRI (if bone metastases are suspected due to clinical signs). Exclusion of the infiltration of any adjacent organs or structures by CT or MRI, indicating an unresectable situation. ECOG performance status of 0, 1, or 2. Estimated life expectancy > 3 months. Female and male patients1 ≥18 years. Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures No previous or preceding cytotoxic or targeted therapy for BTC or IGBC. No previous malignancy within five years or concomitant malignancy, except non-melanomatous skin cancer or adequately treated in situ cervical cancer. No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last three months, significant arrhythmia). Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent. No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial. A) Females of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 7 months after the last study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (has not had ≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. B) Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm, as defined below: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for at least 3 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period. Men with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy. No pregnancy or lactation. Adequate hematologic function: ANC ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 9 g/dl or ≥ 5.59 mmol/L; prior transfusions for patients with low hemoglobin are allowed Adequate liver function as measured by serum transaminases (AST and ALT) ≤ 5 x ULN and bilirubin ≤ 3 x ULN. Adequate renal function, i.e. serum creatinine ≤ 1.5 x ULN, glomerular filtration rate ≥ 60 mL/min determined with the MDRD formula. Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to randomization. No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy (patients on long-term antibiotics are eligible provided signs of active infection have been resolved). No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days or five half-lives (whichever is longer) prior to randomization. Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women

Ausschlusskriterien

  1. Known hypersensitivity against gemcitabine or cisplatin
  2. Other known contraindications to gemcitabine or cisplatin
  3. Unresolved biliary tract obstruction
  4. Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment.
  5. Clinically significant valvular defect
  6. Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix
  7. Locally unresectable tumor or metastatic disease:

    • Radiological evidence suggesting inability to resect with curative intent whilst maintaining adequate vascular inflow and outflow, and sufficient future liver remnant
    • Radiological evidence of direct invasion into adjacent organs
    • Radiological evidence of extrahepatic metastatic disease
  8. Other severe internal disease or acute infection
  9. Chronic inflammatory bowel disease
  10. Receiving chronic antiplatelet therapy, including aspirin (Once-daily aspirin use (maximum dose 325 mg/day) is permitted), nonsteroidal anti-inflammatory drugs (including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents.
  11. History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during 3 months prior to randomization.
  12. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites.
  13. On-treatment participation in another clinical study 30 days or five half-lives (whichever is longer) prior to inclusion and during the study
  14. Pregnant or breast feeding patient, or patient is planning to become pregnant within 7 months after the end of treatment.
  15. Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
  16. Any other concurrent antineoplastic treatment including irradiation

Therapie

Intervention

Substanz

Cisplatin,Gemcitabin

Sonstiges

Zuständige Gesamtstudie

Sponsor

Krankenhaus Nordwest - Frankfurt a.M.

Leiter der klinischen Prüfung (LKP)

Studiengruppen/-zentrale

Kontakt Klinische Studien

CIO Aachen: Uniklinik RWTH Aachen, +49 (0) 241 80-85490

CIO Bonn: Uniklinik Bonn, +49 (0) 228 287-16036

CIO Köln: Uniklinik Köln, +49 (0) 221 478-0

CIO Düsseldorf: Uniklinik Düsseldorf, +49 (0) 211 81-04150 (Mo-Do)