Clinical Trial of Chemotherapy Combination Cisplatin-Fluorouracil-Afatinib in Patients With Inoperable Gastric Cancer

NCT01743365 | Completed Phase 2

• 2 other identifiers: HE7/122011-006198-25
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 15

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  At an average of 6 months for each patient

Secondary Outcomes (4)

• Evaluation of Overall Survival (OS)

  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)

  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

  Assessed up to 36 months

• Value of prognostic and/or predictive biomarkers measured in tissue and blood samples

  Tumor blocks and blood samples will be collected at baseline

Study Arms (1)

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.

Drug: Cisplatin-5FU-Afatinib

Interventions

Cisplatin-5FU-Afatinib DRUG

Cisplatin-5FU-Afatinib

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hellenic Cooperative Oncology Group: lead
• Boehringer Ingelheim: collaborator

Study Sites (15)

2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital

Athens, 11522, Greece

Location

Dept of Medical Oncology, 251 Air Force Hospital

Athens, 11525, Greece

Location

2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio"

Athens, 11527, Greece

Location

Oncology Section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra"

Athens, 11528, Greece

Location

Division of Oncology, 2nd Dept of Internal Medicine, University Hospital "Attikon"

Athens, 12462, Greece

Location

2nd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, 14564, Greece

Location

3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, 14564, Greece

Location

3rd Dept of Medical Oncology, Hygeia Hospital

Athens, 15123, Greece

Location

1st Dept of Medical Oncology, Metropolitan Hospital

Athens, 18547, Greece

Location

2nd Dept of Medical Oncology, Metropolitan Hospital

Athens, 18547, Greece

Location

Dept of Medical Oncology, University Hospital of Heraklion

Heraklion, 71110, Greece

Location

Dept of Medical Oncology, Ioannina University Hospital

Ioannina, 45110, Greece

Location

Division of Oncology, Dept of Internal Medicine, University Hospital of Patras

Pátrai, 26504, Greece

Location

Dept of Medical Oncology, Papageorgiou General Hospital

Thessaloniki, 56429, Greece

Location

Dept of Medical Oncology, Thermi Clinic S.A

Thessaloniki, 57001, Greece

Location

Related Publications (1)

• 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.

  PMID: 34003074 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• George Pentheroudakis, Ass.Prof

  Dept of Medical Oncology, Ioannina University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: December 6, 2012
• Study Start: February 11, 2013
• Primary Completion: June 15, 2019
• Study Completion: July 29, 2019
• Last Updated: September 4, 2019

Record last verified: 2019-08

Locations

GR (15)