Study of Alofanib in Patients With Metastatic Gastric Cancer

Phase 1

• Conditions: Gastric Cancer
• Interventions: Drug: Alofanib

• Registration Number: NCT04071184
• Lead Sponsor: Russian Pharmaceutical Technologies

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-26
• Study First Submitted: 2019-08-13
• Study First Submitted QC: 2019-08-26
• Study First Posted: 2019-08-28
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-25
• Last Update Posted: 2019-09-26
• Primary Completion: 2020-10-01
• Study Completion: 2020-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose cohorts	Alofanib	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.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) or Recommended phase 2 dose (RP2D)	6 months	The highest dose of an alofanib that does not cause unacceptable side effects and recommended

Secondary Outcome Measures

Name	Time	Method
Tmax	1 month	Time of Maximum concentration observed
Cmax	1 month	Peak Plasma Concentration (Cmax), the maximum concentration recorded
t1/2	1 month	Elimination half-life, the time taken for the plasma concentration to fall by half its original value
AUC	1 month	Area under the plasma concentration versus time curve
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	12 months	Rate of AEs and SAEs according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0
CL	1 month	blood clearance
Vd	1 month	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
Progression-free survival (PFS)	12 months	PFS is defined as the time from treatment start to disease progression or death from any cause
Overall survival (OS)	12 months	OS is defined as the time from treatment start to death from any cause
Objective response rate (ORR)	12 months	ORR is the proportion of patients with tumor size reduction.

Trial Locations

Locations (4)

Omsk Regional Cancer Center; 🇷🇺 Omsk, Russian Federation

St. Petersburg City Cancer Center; 🇷🇺 Saint Petersburg, Russian Federation

N.N.Blokhin Russian Cancer Research Centre, Dept. of Clinical Pharmacology and Chemotherapy; 🇷🇺 Moscow, Russian Federation

Rostov Research Institute of Oncology; 🇷🇺 Rostov-on-Don, Russian Federation