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Incidental Gallbladder CarcinomaPhase 3GAINNCT03673072

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

A Phase 3 study testing Gemcitabine, Cisplatin and Oncologically radical margin-free (R0) resection in people with Incidental Gallbladder Carcinoma and Biliary Tract Cancer, run by Krankenhaus Nordwest at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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) Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gemcitabine, Cisplatin and Oncologically radical margin-free (R0) resection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
1 siteGermany
Study dates
1 Jul 2019to 10 Oct 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
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  • 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.
  • 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.
  • 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 institutional ULN, a calculated glomerular filtration rate ≥ 30 mL/min.
  • 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 <1 year after the onset of menopause Please note that after randomization for patients in Arm A the histological confirmation of BTC or GBC must be performed before administering chemotherapy. For IGBC histological confirmation should already have been performed.
  • For Arm B patients the histological confirmation can be performed after surgery with material from the surgery.

Who cannot join

  • 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
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  • 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.
  • On-treatment participation in another clinical study 30 days or five half-lives (whichever is longer) prior to inclusion and during the study
  • 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)
  • Any other concurrent antineoplastic treatment including irradiation

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Krankenhaus Nordwest gGmbH

    Frankfurt, 60488

Other trials in Germany

About this study

Official title: 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 -

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)

Read the detailed description

The aim of the study is to investigate whether induction chemotherapy followed by radical re-resection (and - if possible - postoperative chemotherapy) in incidental gallbladder carcinoma (IGBC) or in front radical resection in biliary tract cancer (BTC) (intrahepatic cholangiocarcinoma (ICC)/ extrahepatic cholangiocarcinoma (ECC)) prolongs overall survival without impaired quality of life compared to immediate radical surgery alone with or without adjuvant chemotherapy (investigator's choice) in patients with IGBC, or BTC (ICC/ECC). One of the most important secondary objectives is to raise awareness for the necessity of a radical second surgery as well as to improve the adherence to the treatment guidelines in IGBC. Further secondary objectives are safety and tolerability of the treatment as well as quality of life.

Being tested
Gemcitabine, Cisplatin, Oncologically radical margin-free (R0) resection, Adjuvant chemotherapy
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GemcitabineDrug

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

  • CisplatinDrug

    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

  • Oncologically radical margin-free (R0) resectionProcedure or surgery

    Oncologically radical margin-free (R0) resection

  • Adjuvant chemotherapyDrug

    Can be selected by Investigator's Choice

Study groups in NCT03673072
Study groupRoleWhat they receive
Arm A (gemcitabine plus cisplatin)ExperimentalPatients 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).
Receives: Drug: Gemcitabine; Drug: Cisplatin; Procedure: Oncologically radical margin-free (R0) resection
Arm B (standard postoperative management)Active comparatorPatients 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.
Receives: Procedure: Oncologically radical margin-free (R0) resection; Drug: Adjuvant chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary efficacy endpoint is overall survival (OS)

    Measured: up to 6 years follow-up

Secondary outcomes (7)

  1. Quality of life (EORTC QLQ-C30)

    "European Organisation for the Research and Treatment of Cancer" Quality of Life Questionnaire Core 30. The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients.

    The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items.

    Each of the multi-item scales includes a different set of items - no item occurs in more than one scale.

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

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

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

    Measured: at 3 and 5 years after randomization

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

    Measured: at 3 and 5 years after randomization

  4. Progression free survival (PFS)

    Measured: up to 6 years after randomization

  5. R0- resection rate

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

  6. Toxicity, graded using CTC adverse events criteria version CTCAE V 5.0

    Measured: up to 6 years after randomization

  7. Number of patients with any serious perioperative morbidity or mortality

    Measured: up to 30 and 90 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2018
  2. Study start1 Jul 2019
  3. Primary completion10 Oct 2024
  4. Study completion10 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03673072
Sponsor's protocol ID
GAIN/GEM/CIS
Other IDs
2017-004444-38, AIO-HEP-0118/ass, 2017
Acronym
GAIN
Status last verified
Nov 2024
First submitted
3 Sep 2018
Last updated
12 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Publications

  • 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.

    PubMed 32059704

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gemcitabine, Cisplatin and Oncologically radical margin-free (R0) resection in people with Incidental Gallbladder Carcinoma and Biliary Tract Cancer, run by Krankenhaus Nordwest at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary efficacy endpoint is overall survival (OS) (time frame: up to 6 years follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03673072, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.

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