advanced esophageal-gastric junction (EGJ)/Gastric cancer Trastuzumab resistant
Conditions
Interventions
Product Name: pemigatinib
Product Code: INCB054828
Pharmaceutical Form: Tablet
INN or Proposed INN: pemigatinib
CAS Number: 1513857-77-6
Current Sponsor code: INCB054828
Other descriptive name: INCB05
Sponsors
Centro Ricerche Cliniche di Verona
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Histologically confirmed advanced or metastatic adenocarcinoma of the stomach and the gastroesophageal junction. •Disease progression within 3 months of the last dose of first-line trastuzumab containing therapy. •Patients must have performed a fresh biopsy (at least 8-10 slides with >20% tumor content) at the baseline of study enrollment. •At least one measurable and evaluable disease site based on response evaluation criteria in solid tumors (RECIST v1.1). •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1. •Age =18, no age upper limit unless patient would be unable to tolerate chemotherapy. •An expected survival of more than 3 months. •Duration from the last therapy is more than 4 weeks for other cytotoxic agents, operation or radiotherapy. •Major organ function has to meet the following criteria o Hemoglobin (Hb)>8 g/dL o PLT >75 X 109/L o ANC >1.5 X 109/L •Absence of pregnacy or breastfeeding. •Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men shall agree to take appropriate methods of contraception during the study until the 8th week post the last administration of study drug. •Patients must be accessible to follow-up and management in the treatment center. •Patient has to voluntarily join the study and sign the Informed Consent Form for the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: •Current evidence of corneal disorder/keratopathy, including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjuntivitis etc, confirmed by ophthalmologic examination. •Any active malignancies except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix. •Poor-controlled arterial hypertension (sistolic blood pressure >140 mmHg and diastolic blood pressure >90 mmHg) despite standard medical management. •Serious cardiovascular disease: II level myocardial ischemia or myocardial infarction, arrhytmia (including QT interval prolongation, for man > 450ms, for woman > 470 ms); III-IV level cardiac function insufficiency, or echocardiography showed that left ventricular ejection fraction (LVEF) 1.0 g). •Total bilirubin = 1.5 × upper limit of normal (ULN; = 2.5 × ULN if Gilbert syndrome or metastatic disease involving liver). •AST and ALT > 2.5 × ULN (AST and ALT > 5 × ULN in the presence of liver metastases). •Creatinine clearance = 30 mL/min based on Cockroft-Gault •Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction). •Serum phosphate > institutional ULN. •Serum calcium outside of the institutional normal range or serum albumin-corrected calcium outside of the institutional normal range when serum albumin is outside of the institutional normal range. •History of calcium/phosphate homeostasis disorder. •History and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification. •Current evidence of significant corneal disorder/keratopathy or retinal disorder, confirmed by ophthalmologic examination. •Factors of high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 2 months; unresected primary lesion in stomach with positive fecal occult blood test (+), ulcerated gastric carcinoma with massive alimentary tract bleeding risk judged by Pis based on gastric endoscopy result. •Abnormal Coagulation (INR >1.5 APTT >1.5 UNL), with tendency of bleed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the 12-weeks progression free survival (PFS-12w) rate in patients with advanced EGJ/gastric cancer HER2-positive at diagnosis and progressed to a first line therapy with trastuzumab receiving INCB0544828 as second-line monotherapy.;Secondary Objective: Efficacy •To determine median progression free survival (PFS) in patient treated with INCB054828 as second line monotherapy. •To determine overall survival (OS) in patient treated with INCB054828 as second line monotherapy. •To determine disease control rate (DCR), number of patient achieving DC (RC/RP/SD). •To determine overall response rate (ORR), including confirmed and unconfirmed, complete and partial response, per Responsive Evaluation Criteria in Solid Tumors (RECIST) 1.1 Safety •To assess immediate mortality and morbidity associated with INCB054828 as second-line monotherapy. •To estimate frequency and severity of adverse events associated with INCB054828 as second-line monotherapy. Quality of life and cost •To determine changes on QoL (daily life activities, nutritional state and weight loss) in patients treated with INCB054828 as second-line therapy. ;Primary end point(s): •12-weeks progression free survival rate, the probability of being progression-free (loco-regional or distant) or death due to any cause at 12-weeks from trial enrollment.;Timepoint(s) of evaluation of this end point: At 12 weeks The efficacy evaluations will take place at screening (this will be considered the reference scan), every 2 cycles (every 6 weeks) for the first 4 cycles and subsequently every 3 cycles (every 9 weeks). For patients who stop treatment for reasons other than disease progression, every effort will be made to continue monitoring the disease by radiographic imaging up to 1) initiation of a new anti-tumor therapy, 2) progression of the documented disease, 3) death, or 4) end of the study, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •OS, time from enrollment to death from any cause. It will be estimated with Kaplan Meier curves. •DCR, number percentage of patients achieving DC (RC/RP/SD). It will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes. •Incidence of toxicity gratergreater than grade 4, using Common Terminology Criteria for Adverse Events version 4.0 (time frame every two weeks during treatment). Toxicity evaluation will be enumeration of all major toxicity, with proportions calculated for each. ;Timepoint(s) of evaluation of this end point: From enrollment to death | — |
Countries
Italy
Contacts
Public ContactCentro Ricerche Cliniche di Verona
Centro Ricerche Cliniche di Verona
Outcome results
None listed