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

NCT03673072 | Completed Phase 3 DMC

• 3 other identifiers: GAIN/GEM/CIS2017-004444-38AIO-HEP-0118/ass
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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 (ICC/ECC)

Conditions

Incidental Gallbladder Carcinoma; Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Primary efficacy endpoint is overall survival (OS)

  up to 6 years follow-up

Secondary Outcomes (7)

• Quality of life (EORTC QLQ-C30)

  every 3 weeks until EOT andt then every 3 months up to 6 years of follow-up

• PFS (Progression free surviva) rates at 3 and 5 years

  at 3 and 5 years after randomization

• OS (overall survival) rates at 3 and 5 years

  at 3 and 5 years after randomization

• Progression free survival (PFS)

  up to 6 years after randomization

• R0- resection rate

  2 weeks after surgery (Arm A: 14 weeks after randomization; Arm B: 2 weeks after randomization)

Study Arms (2)

Arm A (gemcitabine plus cisplatin)

EXPERIMENTAL

Patients assigned to arm A will receive treatment with gemcitabine plus cisplatin. Chemotherapy will be administered for 3 cycles preoperatively (neoadjuvant part) and for 3 cycles postoperatively (adjuvant part).

Drug: Gemcitabine; Drug: Cisplatin; Procedure: Oncologically radical margin-free (R0) resection

Arm B (standard postoperative management)

ACTIVE COMPARATOR

Patients assigned to arm B will receive surgery directly, without receiving perioperative chemotherapy (Standard of Care / SOC). After surgery, adjuvant chemotherapy can be administered by investigator's choice.

Procedure: Oncologically radical margin-free (R0) resection; Drug: Adjuvant chemotherapy

Interventions

Gemcitabine DRUG

Gemcitabine (1000 mg/m2) in 250-500 ml 0.9% saline every three weeks on days 1 and 8 intravenously

Arm A (gemcitabine plus cisplatin)

Cisplatin DRUG

Cisplatin (25 mg/m2) every three weeks on days 1 and 8 intravenously, in 1000 ml 0.9% saline with KCl 20 mmol and MgSO4 8 mmol during the one hour cisplatin infusion followed by 500 ml 0.9% saline over 30 minutes prior to gemcitabine; with adequate pre- and posthydration

Arm A (gemcitabine plus cisplatin)

Oncologically radical margin-free (R0) resection PROCEDURE

Oncologically radical margin-free (R0) resection

Arm A (gemcitabine plus cisplatin); Arm B (standard postoperative management)

Adjuvant chemotherapy DRUG

Can be selected by Investigator's Choice

Arm B (standard postoperative management)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Incidental gallbladder carcinoma (IGBC), gallbladder carcinoma (GBC) () 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), and for IGBC/GBC prior Cholecystectomy is allowed.
• 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/GBC.
• No previous malignancy within two years or concomitant malignancy, except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate 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 6 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.

You may not qualify if:

• Known hypersensitivity against gemcitabine or cisplatin
• Other known contraindications to gemcitabine or cisplatin
• Clinically significant valvular defect
• Past or current history of other malignancies not curatively treated and without evidence of disease for more than two years, except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer
• 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
• Other severe internal disease or acute infection
• Chronic inflammatory bowel disease
• 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.
• 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.
• Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites.
• Pregnant or breast feeding patient, or patient is planning to become pregnant within 7 months after the end of treatment.
• Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)

Sponsors & Collaborators

• Krankenhaus Nordwest: lead
• German Research Foundation: collaborator

Study Sites (1)

Krankenhaus Nordwest gGmbH

Frankfurt, 60488, Germany

Location

Related Publications (1)

• Goetze TO, Bechstein WO, Bankstahl US, Keck T, Konigsrainer A, Lang SA, Pauligk C, Piso P, Vogel A, Al-Batran SE. 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 (ICC/ECC) - a phase III study of the German registry of incidental gallbladder carcinoma platform (GR)- the AIO/ CALGP/ ACO- GAIN-trial. BMC Cancer. 2020 Feb 14;20(1):122. doi: 10.1186/s12885-020-6610-4.

  PMID: 32059704 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Gemcitabine; Cisplatin; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Thorsten O Goetze, PD Dr.

  Krankenhaus Nordwest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2018
• First Posted: September 17, 2018
• Study Start: July 1, 2019
• Primary Completion: October 10, 2024
• Study Completion: October 10, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)