Gastric CancerPhase 2A-GAPPNCT01743365
Clinical Trial of Chemotherapy Combination Cisplatin-Fluorouracil-Afatinib in Patients With Inoperable Gastric Cancer
A Phase 2 study testing Cisplatin-5FU-Afatinib in people with Gastric Cancer and Gastroesophageal Junction Cancer, run by Hellenic Cooperative Oncology Group at 15 sites in Greece.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of the combination of Cisplatin,5-Fluorouracil(5FU) and Afatinib as first-line therapy in patients with advanced gastric or gastroesophageal junction cancer. The study will include 55 patients in all. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Cancer, Gastroesophageal Junction Cancer
- What is being tested?
- Cisplatin-5FU-Afatinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 15 sitesGreece
- Study dates
- 11 Feb 2013to 29 Jul 2019
- Phase
- Phase 2
- 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
- Patients with histological or cytological diagnosis of gastric and/or gastroesophageal junction adenocarcinoma/carcinoma.
- Locally advanced or metastatic inoperable disease.
- Life expectancy ≥12 weeks.
- Patients who may have undergone any type of palliative treatment for localised disease, including surgical approaches and palliative radiotherapy, but not in the last four weeks before the trial.
- Adequate bone marrow, hepatic and renal functional reserves (ANC≥1500mm3, PLT≥100mm3, GFR≥50ml/min by Gault Formula, bilirubin <1.5x, Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) <2.5x upper normal limit or 5x in the presence of hepatic metastases).
- Patients must be able to swallow pharmaceutical tablets and to be eligible to receive intravenous chemotherapy.
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- Men or women patients must be at least 18 years old.
- Performance Status Scale 0 or 1 (ECOG).
- Measurable disease according to RECIST 1.1.
- Left ventricular ejection fraction (LVEF) ≥50% (ECHO or MUGA).
- Provision of patient informed consent for participation in the study and for the use of biological material for research purposes.
- Willingness and ability to comply with scheduled medical visits, therapeutic treatment programmes, laboratory testing and other study procedures.
Who cannot join
- Previous systemic first-line therapy.
- Previous therapy with EGFR/HER Tyrosine Kinase Inhibitor (TKI) or other experimental agent.
- Diagnosis of a second malignancy, except basal cell carcinoma of the squamous epithelium or in situ carcinoma of any organ, for which an appropriate treatment has been administered without indications of relapse for 12 months.
- Presence of uncontrolled, active brain metastases (controlled brain metastases are considered those that have been irradiated and have remained stable for at least 4 weeks after radiation therapy).
- Diagnosis of spinal cord compression or carcinomatous meningitis.
- Any of the following that has occurred within 12 months before the start of the study treatment: myocardial infarction, serious or unstable angina pectoris, aortic-coronary or peripheral bypass surgery, symptomatic heart failure, vascular stroke, or transient ischemic attack, or pulmonary embolism.
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- Continuing grade ≥2 heart rate abnormalities; atrial fibrillation of any grade.
- Hypertension uncontrolled by medication treatment (>150/100 mm/Hg despite the administration of best medical therapy).
- In the case of previous irradiation of locally advanced disease, absence of measurable tumor sites outside the irradiation field.
- Presence of any other disease which in the opinion of the doctor responsible constitutes a contraindication for the administration of cisplatin, 5FU or afatinib.
- Diagnosed human immunodeficiency virus (HIV) or disease associated with Acquired Immunodeficiency Syndrome (AIDS).
- Pregnancy or lactation. Female patients must be surgically sterilised, menopausal, or must consent to use effective contraception throughout the course of the trial.All female patients with reproduction ability must undergo a pregnancy test (serum or urine). The effective contraceptive technique will be determined by the main investigator or a person authorized by the investigator.
- Any other serious, acute or chronic, medical or psychiatric condition or laboratory analysis finding which, in the investigator's opinion, could create excessive danger as regards the patient's participation in the trial or administration of the trial medication may render a patient ineligible for inclusion in the trial.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Greece15 sites
2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital
Athens, 11522
Dept of Medical Oncology, 251 Air Force Hospital
Athens, 11525
2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio"
Athens, 11527
Oncology Section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra"
Athens, 11528
Division of Oncology, 2nd Dept of Internal Medicine, University Hospital "Attikon"
Athens, 12462
2nd Dept of Medical Oncology, Agii Anargiri Cancer Hospital
Athens, 14564
3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital
Athens, 14564
3rd Dept of Medical Oncology, Hygeia Hospital
Athens, 15123
1st Dept of Medical Oncology, Metropolitan Hospital
Athens, 18547
2nd Dept of Medical Oncology, Metropolitan Hospital
Athens, 18547
Dept of Medical Oncology, University Hospital of Heraklion
Heraklion, 71110
Dept of Medical Oncology, Ioannina University Hospital
Ioannina, 45110
Division of Oncology, Dept of Internal Medicine, University Hospital of Patras
Pátrai, 26504
Dept of Medical Oncology, Papageorgiou General Hospital
Thessaloniki, 56429
Dept of Medical Oncology, Thermi Clinic S.A
Thessaloniki, 57001
About this study
Official title: A Phase II, Single-arm Clinical Trial of Administration of Cisplatin and 5- Fluorouracil With Afatinib as First-line Therapy in Patients With Inoperable Gastric or Gastroesophageal Junction Cancer
The purpose of this study is to evaluate the efficacy and safety of the combination of Cisplatin,5-Fluorouracil(5FU) and Afatinib as first-line therapy in patients with advanced gastric or gastroesophageal junction cancer. The study will include 55 patients in all. The patients will receive open-label Cisplatin intravenous 75mg/m2 on Day 1, 5FU 750mg/m2 at 24-hour intravenous infusion on Days 1-4, and Afatinib 40mg per os on Days 3-5, 8-12, 15-19.
The administration of Afatinib will start on Day 3 of each therapy cycle with an administration interval on each weekend ("Weekday on, Weekend off") for 21 days. Instructions are given on the dose reduction scheme in the presence of toxicity. The administration of the combination Cisplatin-5FU-Afatinib will be continued until disease progression, appearance of significant toxicity, completion of 6 treatment cycles, or withdrawal of consent. At completion of 6 cycles of the combination, in the absence of disease progression, the administration of Afatinib as maintenance monotherapy will be continued until disease progression, appearance of significant toxicity, or withdrawal of consent at the weekday on-weekend off schedule. Imaging will be applied once every 8 weeks, and once every 12 weeks in the Afatinib maintenance therapy phase.
- Conditions
- Gastric Cancer, Gastroesophageal Junction Cancer
- Being tested
- Cisplatin-5FU-Afatinib
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cisplatin-5FU-AfatinibDrug
| Study group | Role | What they receive |
|---|---|---|
| Cisplatin-5FU-Afatinib | Experimental | Cisplatin 75mg/m2 iv administered on Day 1, 5FU 750mg/m2 at 24-hour iv infusion on Days 1-4, Afatinib (BIBW-2992) 40mg per os on Days 3-5, 8-12, 15-19 of each cycle. Administration of Afatinib will start on Day 3 of each cycle with an administration interval on each weekend ("Weekday on, Weekend off") for 21 days. The administration of the combination Cisplatin-5FU-Afatinib will be continued until disease progression, appearance of significant toxicity, completion of 6 cycles, or withdrawal of consent. At completion of 6 cycles of the combination, in the absence of disease progression, the administration of Afatinib as maintenance monotherapy will be continued until disease progression, appearance of significant toxicity, or withdrawal of consent at the weekday on-weekend off schedule. Receives: Drug: Cisplatin-5FU-Afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Imaging will be performed once every 8 weeks during treatment with cisplatin-5FU-afatinib (6 cycles), and once every 12 weeks in the Afatinib maintenance therapy phase.
Measured: At an average of 6 months for each patient
Secondary outcomes (4)
Evaluation of Overall Survival (OS)
Measured: OS will be calculated from the date of treatment initiation to the date of death from any cause assessed up to 36 months.
Evaluation of Progression-Free Survival (PFS)
Measured: PFS will be calculated from the date of treatment initiation to the date of disease progression or date of death, assessed up to 36 months.
Assessment of safety and tolerability
Distribution of Adverse Events (AEs) according to severity grade.
Evaluation of AEs will be performed:
On Day 1 and day 10 in cycle 1,on Day 1 in cycles 2-6 (every 21 days) and on Day 1 during maintenance treatment with afatinib (every 4 weeks).
Measured: Assessed up to 36 months
Value of prognostic and/or predictive biomarkers measured in tissue and blood samples
Immunochemical expression of proteins/messenger ribonucleic acid (mRNA) of the tumor that can be linked to the efficacy / safety of the treatment, the tumor angiogenesis and the mechanism of action of the combination cisplatin/5FU/Afatinib.
In bioptic material for gastric or gastroesophageal adenocarcinoma:
- Epidermal Growth Factor Receptor (EGFR) immunohistochemical expression;
- EGFR gene amplification (chromosome 7 gene number by FISH);
- mRNA levels of the EGFR ligands epiregulin and amphiregulin;
- Kirsten Rat Sarcoma (KRAS) mutations;
- Human Epidermal Growth Factor Receptor 2 (HER2) immunohistochemical expression and gene amplification
- HER2 p95, Human Epidermal Growth Factor Receptor 3 (HER3), Human Epidermal Growth Factor Receptor 4 (HER4) immunohistochemical and mRNA expression
In peripheral blood and plasma:HER2 shed extracellular domain (ECD)
There may be additions to the biomarkers to be analysed, dependent on the clinical and bibliographical data.
Measured: Tumor blocks and blood samples will be collected at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study start11 Feb 2013
- Primary completion15 Jun 2019
- Study completion29 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastric CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hellenic Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- George Pentheroudakis, Ass.Prof, Study chair, Dept of Medical Oncology, Ioannina University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01743365
- Sponsor's protocol ID
- HE7/12
- Other IDs
- 2011-006198-25
- Acronym
- A-GAPP
- Status last verified
- Aug 2019
- First submitted
- 28 Nov 2012
- Last updated
- 4 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Zarkavelis G, Samantas E, Koliou GA, Papadopoulou K, Mauri D, Aravantinos G, Batistatou A, Pazarli E, Tryfonopoulos D, Tsipoura A, Bobos M, Psyrri A, Makatsoris T, Petraki C, Pectasides D, Fountzilas G, Pentheroudakis G. AGAPP: efficacy of first-line cisplatin, 5-fluorouracil with afatinib in inoperable gastric and gastroesophageal junction carcinomas. A Hellenic Cooperative Oncology Group study. Acta Oncol. 2021 Jun;60(6):785-793. doi: 10.1080/0284186X.2021.1912822. Epub 2021 May 18.
PubMed 34003074
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single-arm Clinical Trial of Administration of Cisplatin and 5- Fluorouracil With Afatinib as First-line Therapy in Patients With Inoperable Gastric or Gastroesophageal Junction Cancer
- ClinicalTrials.gov ID
- NCT01743365
- Acronym / sponsor ID
- A-GAPP / HE7/12
- Conditions
- Gastric Cancer, Gastroesophageal Junction Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Hellenic Cooperative Oncology GroupUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- 11 Feb 2013 (actual)
- Primary completion
- 15 Jun 2019 (actual)
- Study completion
- 29 Jul 2019 (actual)
- First posted
- 6 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of the combination of Cisplatin,5-Fluorouracil(5FU) and Afatinib as first-line therapy in patients with advanced gastric or gastroesophageal junction cancer. The study will include 55 patients in all. The patients will receive open-label Cisplatin intravenous 75mg/m2 on Day 1, 5FU 750mg/m2 at 24-hour intravenous infusion on Days 1-4, and Afatinib 40mg per os on Days 3-5, 8-12, 15-19.
The administration of Afatinib will start on Day 3 of each therapy cycle with an administration interval on each weekend ("Weekday on, Weekend off") for 21 days. Instructions are given on the dose reduction scheme in the presence of toxicity. The administration of the combination Cisplatin-5FU-Afatinib will be continued until disease progression, appearance of significant toxicity, completion of 6 treatment cycles, or withdrawal of consent. At completion of 6 cycles of the combination, in the absence of disease progression, the administration of Afatinib as maintenance monotherapy will be continued until disease progression, appearance of significant toxicity, or withdrawal of consent at the weekday on-weekend off schedule. Imaging will be applied once every 8 weeks, and once every 12 weeks in the Afatinib maintenance therapy phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cisplatin-5FU-Afatinib | Experimental | Drug: Cisplatin-5FU-AfatinibCisplatin 75mg/m2 iv administered on Day 1, 5FU 750mg/m2 at 24-hour iv infusion on Days 1-4, Afatinib (BIBW-2992) 40mg per os on Days 3-5, 8-12, 15-19 of each cycle. Administration of Afatinib will start on Day 3 of each cycle with an administration interval on each weekend ("Weekday on, Weekend off") for 21 days. The administration of the combination Cisplatin-5FU-Afatinib will be continued until disease progression, appearance of significant toxicity, completion of 6 cycles, or withdrawal of consent. At completion of 6 cycles of the combination, in the absence of disease progression, the administration of Afatinib as maintenance monotherapy will be continued until disease progression, appearance of significant toxicity, or withdrawal of consent at the weekday on-weekend off schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with histological or cytological diagnosis of gastric and/or gastroesophageal junction adenocarcinoma/carcinoma.
- Locally advanced or metastatic inoperable disease.
- Life expectancy ≥12 weeks.
- Patients who may have undergone any type of palliative treatment for localised disease, including surgical approaches and palliative radiotherapy, but not in the last four weeks before the trial.
- Adequate bone marrow, hepatic and renal functional reserves (ANC≥1500mm3, PLT≥100mm3, GFR≥50ml/min by Gault Formula, bilirubin <1.5x, Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) <2.5x upper normal limit or 5x in the presence of hepatic metastases).
Key exclusion criteria (13 listed)
- Previous systemic first-line therapy.
- Previous therapy with EGFR/HER Tyrosine Kinase Inhibitor (TKI) or other experimental agent.
- Diagnosis of a second malignancy, except basal cell carcinoma of the squamous epithelium or in situ carcinoma of any organ, for which an appropriate treatment has been administered without indications of relapse for 12 months.
- Presence of uncontrolled, active brain metastases (controlled brain metastases are considered those that have been irradiated and have remained stable for at least 4 weeks after radiation therapy).
- Diagnosis of spinal cord compression or carcinomatous meningitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cisplatin-5FU-Afatinib | Drug | Cisplatin-5FU-Afatinib |
Primary outcome
Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Time frame: At an average of 6 months for each patient
Imaging will be performed once every 8 weeks during treatment with cisplatin-5FU-afatinib (6 cycles), and once every 12 weeks in the Afatinib maintenance therapy phase.
4 secondary outcomes
Evaluation of Overall Survival (OS)
Time frame: OS will be calculated from the date of treatment initiation to the date of death from any cause assessed up to 36 months.
Evaluation of Progression-Free Survival (PFS)
Time frame: PFS will be calculated from the date of treatment initiation to the date of disease progression or date of death, assessed up to 36 months.
Assessment of safety and tolerability
Time frame: Assessed up to 36 months
Value of prognostic and/or predictive biomarkers measured in tissue and blood samples
Time frame: Tumor blocks and blood samples will be collected at baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- Derived from this study: PubMed 34003074Zarkavelis G, Samantas E, Koliou GA, Papadopoulou K, Mauri D, Aravantinos G, Batistatou A, Pazarli E, Tryfonopoulos D, Tsipoura A, Bobos M, Psyrri A, Makatsoris T, Petraki C, Pectasides D, Fountzilas G, Pentheroudakis G. AGAPP: efficacy of first-line cisplatin, 5-fluorouracil with afatinib in inoperable gastric and gastroesophageal junction carcinomas. A Hellenic Cooperative Oncology Group study. Acta Oncol. 2021 Jun;60(6):785-793. doi: 10.1080/0284186X.2021.1912822. Epub 2021 May 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George Pentheroudakis, Ass.Prof study chair
Dept of Medical Oncology, Ioannina University Hospital
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cisplatin-5FU-Afatinib in people with Gastric Cancer and Gastroesophageal Junction Cancer, run by Hellenic Cooperative Oncology Group at 15 sites in Greece.
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 12 inclusion and 13 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 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Greece. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (time frame: At an average of 6 months for each patient). 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 NCT01743365, 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 4 Sep 2019; AzTrials last refreshed its copy on 8 Nov 2026.