Study of Alofanib in Patients With Metastatic Gastric Cancer

Study Overview
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Brief Summary
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This is a non-randomized multicenter phase 1b clinical trial of the safety and pharmacokinetics, as well as the preliminary efficacy of monotherapy with alofanib, an allosteric fibroblast growth factor receptor 2 inhibitor, in patients with advanced gastric cancer who have exhausted the resource of standard therapy.

Official Title
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Phase 1b Clinical Study of the Safety and Pharmacokinetics of Alofanib in Patients With Metastatic Gastric Cancer Resistant to Standard Therapy

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Alofanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed gastric cancer (adenocarcinoma) Progression of the disease (clinical and/or radiological) on previous standard systemic therapy Measurable lesions according to the RECIST 1.1 criteria Possibility to assess the amplification of FGFR2, fusion of FGFR2 genes, overexpression of FGFR2, phosphorylation of FRS2 ECOG PS 0-2 Age >= 18 years old Adequate function of organs Absence of any psychological, family, social or geographical circumstances that could potentially serve as obstacles to the implementation of the study Patients capable of childbearing should use an effective method of contraception Signed Informed Consent Exclusion Criteria: Participation in another clinical study and concomitant treatment with any research drug or any study of antitumor therapy, including radiation, within 28 days before inclusion in this study Presence of metastases in the central nervous system and / or carcinoma of the meninges at the time of inclusion in the study Presence or history of present signs of any condition, therapy or laboratory abnormalities that could limit the interpretation of the results of this study Any malignant tumor within the previous 5 years, with the exception of adequately cured cervical cancer in situ or squamous cell skin cancer, or basal cell skin cancer with limited growth, subject to adequate control over the course of this disease Pregnancy Known positive status for human immunodeficiency virus (HIV) or active hapatitis B and C Surgery within 7 days before the first dose of the study drug Signs of bleeding or hemorrhagic diathesis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose cohorts<br>Part 1 (dose escalation): 3+3 design will be used. Alofanib (dose levels of 50, 100, 165, 250, 350 mg/m2) will be given i.v. daily (1-5 days on, 6-7 days off, every week) till progression or unacceptable toxicity. Part 2 (dose expansion): Afterwards the dosing regimen identified in Part 1 will be evaluated in a single-arm study focused on clinical efficacy. | Drug: Alofanib<br>* Five dose cohorts and expanded cohort will be included<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) or Recommended phase 2 dose (RP2D) | The highest dose of an alofanib that does not cause unacceptable side effects and recommended | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Peak Plasma Concentration (Cmax), the maximum concentration recorded | 1 month | 
| Tmax | Time of Maximum concentration observed | 1 month | 
| AUC | Area under the plasma concentration versus time curve | 1 month | 
| t1/2 | Elimination half-life, the time taken for the plasma concentration to fall by half its original value | 1 month | 
| CL | blood clearance | 1 month | 
| Vd | Volume of distribution, the theoretical volume that would be necessary to contain the total amount of an alofanib at the same concentration that it is observed in the plasma | 1 month | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) | Rate of AEs and SAEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 12 months | 
| Progression-free survival (PFS) | PFS is defined as the time from treatment start to disease progression or death from any cause | 12 months | 
| Overall survival (OS) | OS is defined as the time from treatment start to death from any cause | 12 months | 
| Objective response rate (ORR) | ORR is the proportion of patients with tumor size reduction. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, metastases, patients with previous treatment failures, FGFR2 abnormalities