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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose cohorts | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alofanib | Drug | Five dose cohorts and expanded cohort will be included |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Peak Plasma Concentration (Cmax), the maximum concentration recorded | 1 month |
| Tmax | Time of Maximum concentration observed | 1 month |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ilya Tsimafeyeu, MD | Contact | +79265646581 | office@ruspharm.com |
| Name | Affiliation | Role |
|---|---|---|
| Ilya Tsimafeyeu, MD | Scientific Adviser | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| N.N.Blokhin Russian Cancer Research Centre, Dept. of Clinical Pharmacology and Chemotherapy | Active, not recruiting | Moscow | 115478 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36907947 | Derived | Tsimafeyeu I, Statsenko G, Vladimirova L, Besova N, Artamonova E, Raskin G, Rykov I, Mochalova A, Utyashev I, Gorbacheva S, Kazey V, Gavrilova E, Dragun N, Moiseyenko V, Tjulandin S. A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancer. Invest New Drugs. 2023 Apr;41(2):324-332. doi: 10.1007/s10637-023-01340-z. Epub 2023 Mar 13. |
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| ID | Term |
|---|---|
| D013274 | Stomach Neoplasms |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000610985 | alofanib |
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| 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 |
| Omsk Regional Cancer Center | Recruiting | Omsk | Russia |
|
| Rostov Research Institute of Oncology | Enrolling by invitation | Rostov-on-Don | Russia |
| St. Petersburg City Cancer Center | Active, not recruiting | Saint Petersburg | Russia |
| D004066 |
| Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |