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Fibroblast Growth Factor (FGFs) / Fibroblast Growth Factor Receptor (FGFRs) Genetic as a Second-line Therapy for Recurrent / Progressive Gastric Cancer With INCB054828 and Paclitaxel a Study to Evaluate the Safety and Efficacy of Combination Therapy.

Primary Purpose

Fibroblast Growth Factors (FGFs)/Fibroblast Growth Factor Receptors (FGFRs) Genetic Aberration Gastric Cancer, INCB054828, Paclitaxel

Status

Recruiting

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

INCB054828, Paclitaxel

About this trial

This is an interventional treatment trial for Fibroblast Growth Factors (FGFs)/Fibroblast Growth Factor Receptors (FGFRs) Genetic Aberration Gastric Cancer, INCB054828, Paclitaxel

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients who agreed in writing to the clinical study consent
Histologically or cytologically confirmed advanced gastric adenocarcinoma. Patients must have experienced objective radiological or disease progress with evidence during or after primary therapy with fluoropyrimidine and platinum.
FGFs / FGFRs have genetic variation on NGS.
Patients whose life expectancy is at least 3 months
If the Eastern Cooperative Oncology Group (ECOG) is 0 or 1
Measurable or assessable lesion based on RECIST 1.1 scale
Must be swallowed, should be able to take oral medication
Possible long-term function to receive chemotherapy.
Patients receiving anti-HER2 therapy for HER2 negative or HER2-positive primary treatment

Exclusion Criteria:

When chemotherapy exceeded the first treatment
Patients with multiple cancers
Severe hypersensitivity reactions to anti-FGFR2 agents either now or in the past
Patients with endocrine metabolic syndrome or history of calcium-phosphate homeostasis
Patients with ectopic neoplasm or history of soft tissue, kidney, large intestine, heart, or abdomen
Corneal lesions such as bullous keratopathy, corneal erosion, corneal erosion, corneal ulcer, corneal inflammation and keratoconjunctivitis were confirmed by ophthalmic examination
Patients with metastasis to the brain or meninges. However, patients who do not have symptoms and do not need treatment can register.
Clinically significant digestive system problems that can cause abnormalities in taking or absorbing clinical drugs
Patients with uncontrollable or significant cardiovascular disease
Patients with systemic infections requiring treatment
Patients who were exposed to paclitaxel at or before the taxane
If you undergo major surgery within 28 days before enrollment for this trial
Patients who received radiotherapy for gastric cancer within 28 days prior to enrollment for this trial. However, the investigation of bone turnover was conducted within 14 days before the registration for this trial
If you received general chemotherapy within 14 days of enrollment for this trial
Patients who are positive for human immunodeficiency virus (HIV-1) antibody test,
HBsAg results positive, HBV viral load greater than 2000 IU / ml (104 copies / ml), or HCV antibody test positive
Patients who are pregnant, lactating, or are likely to be pregnant
Anemia and hair loss are excluded if previous chemotherapy treatment has toxicity that is not recovered below grade 2.
Patients who are judged to have lost their ability to cope with dementia or other comorbid conditions
Other Patients who the examiner or the examiner deemed inappropriate for the clinical trial.

Sites / Locations

Yonsei University Health System, Severance HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

phase> INCB054828 begins with oral administration of 13.5 mg once a day. Paclitaxel is administered intravenously every week at 80mg / m2. (Days 1, 8 and 15) It is one cycle of 4 weeks and it is administered until the time of disease progression. phase> INCB54828 is dosed at the dose specified in phase 1. Paclitaxel is administered intravenously every week at 80mg / m2. (Days 1, 8 and 15) It is one cycle of 4 weeks and it is administered until the time of disease progression

Outcomes

Primary Outcome Measures

MTD

Part 1, Phase Ib Maximum Tolerated dose (MTD)

Recommended phase 2 dose (RP2D)

Part 1, Phase Ib Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).

PFS

Prart 2, Phase II Progression-free survival (PFS): PFS is defined as the interval between the date of first dose and the earliest date of disease progression or death due to any cause.

Secondary Outcome Measures

ORR

Objective Response Rate (ORR): The duration of response. ORR is defined as the percentage of subjects with a confirmed CR or PR per RECIST v1.1

DCR

Disease Control Rate (DCR): DCR is the proportion of randomized patients achieving a best overall response of CR, PR, or SD.

Overall Survival (OS): OS is the time from the date of first dose and the date of death from any cause.

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Safety and tolerability of the Varlitinib and Paclitaxel combination therapy as determined by: adverse events (categorized in accordance with CTCAE 4.03).

Full Information

NCT ID

NCT05529667

First Posted

August 16, 2022

Last Updated

September 6, 2022

Sponsor

Yonsei University

1. Study Identification

Unique Protocol Identification Number

NCT05529667

Brief Title

Fibroblast Growth Factor (FGFs) / Fibroblast Growth Factor Receptor (FGFRs) Genetic as a Second-line Therapy for Recurrent / Progressive Gastric Cancer With INCB054828 and Paclitaxel a Study to Evaluate the Safety and Efficacy of Combination Therapy.

Official Title

An Open Label, Single-Arm, Multi-center Phase Ib/II Study to Evaluate the Safety and Efficacy of INCB054828 in Combination With Paclitaxel as a Second Line Treatment in Recurrent/Advanced Gastric Cancer With FGFs/FGFRs Genetic Aberration.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 27, 2019 (Actual)

Primary Completion Date

October 27, 2022 (Anticipated)

Study Completion Date

April 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study was conducted as a second-line treatment of recurrent / progressive gastric cancer patients with FGFs / FGFRs genetic mutations in the Ib / II clinical trial. The maximum maximal tolerated dose (MTD) and 2-phase recommended dose in combination with INCB054828 and paclitaxel (recommended phase II dose, RP2D), and evaluate the safety and clinical efficacy of this combination therapy. This study consists of two steps: Phase 1 is a dose escalation study to determine the maximum tolerated dose and 2-phase recommended dose of weekly paclitaxel and INCB054828 combination therapy, and Phase 2 is the dose escalation study in combination with INCB054828 and paclitaxel Assess safety and tolerability and identify antitumor effects in stomach cancer with FGFs / FGFRs genetic mutations.

Detailed Description

phase> - Approximately 3-12 patients will be enrolled. The dose escalation will be three patients registered for each cohort until the first dose-limiting toxicity appears during the four weeks of treatment and observation. 13.5mg, once a day begins to take. The paclitaxel is administered once a week for three consecutive weeks and then for one week, followed by a total of four weeks in one cycle. phase> Phase 2 studies will be extended to a total of 30 patients with a two-phase recommended dose. Patients will be treated until the time of disease progression, intolerable toxicity, rejection of the patient, or withdrawal of consent. In its pre-screening phase, its next generation sequencing (NGS) is performed. Patients with FGFs / FGFRs genetic abnormalities may be enrolled in this study. If a patient has multiple genetic abnormalities, he or she will first be enrolled in a treatment group that targets a rare genetic abnormality. Registered patients will be treated on a continuous basis every four weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fibroblast Growth Factors (FGFs)/Fibroblast Growth Factor Receptors (FGFRs) Genetic Aberration Gastric Cancer, INCB054828, Paclitaxel

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

INCB054828, Paclitaxel

Intervention Description

phase 1> - Approximately 3-12 patients will be enrolled. The dose escalation will be three patients registered for each cohort until the first dose-limiting toxicity appears during the four weeks of treatment and observation. phase 2> Phase 2 studies will be extended to a total of 30 patients with a two-phase recommended dose. Patients will be treated until the time of disease progression, intolerable toxicity, rejection of the patient, or withdrawal of consent.

Primary Outcome Measure Information:

Title

MTD

Description

Part 1, Phase Ib Maximum Tolerated dose (MTD)

Time Frame

4 weeks

Title

Recommended phase 2 dose (RP2D)

Description

Part 1, Phase Ib Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).

Time Frame

4 weeks

Title

PFS

Description

Prart 2, Phase II Progression-free survival (PFS): PFS is defined as the interval between the date of first dose and the earliest date of disease progression or death due to any cause.

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

ORR

Description

Objective Response Rate (ORR): The duration of response. ORR is defined as the percentage of subjects with a confirmed CR or PR per RECIST v1.1

Time Frame

3 years

Title

DCR

Description

Disease Control Rate (DCR): DCR is the proportion of randomized patients achieving a best overall response of CR, PR, or SD.

Time Frame

3 years

Title

Description

Overall Survival (OS): OS is the time from the date of first dose and the date of death from any cause.

Time Frame

3 years

Title

Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Description

Safety and tolerability of the Varlitinib and Paclitaxel combination therapy as determined by: adverse events (categorized in accordance with CTCAE 4.03).

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients who agreed in writing to the clinical study consent Histologically or cytologically confirmed advanced gastric adenocarcinoma. Patients must have experienced objective radiological or disease progress with evidence during or after primary therapy with fluoropyrimidine and platinum. FGFs / FGFRs have genetic variation on NGS. Patients whose life expectancy is at least 3 months If the Eastern Cooperative Oncology Group (ECOG) is 0 or 1 Measurable or assessable lesion based on RECIST 1.1 scale Must be swallowed, should be able to take oral medication Possible long-term function to receive chemotherapy. Patients receiving anti-HER2 therapy for HER2 negative or HER2-positive primary treatment Exclusion Criteria: When chemotherapy exceeded the first treatment Patients with multiple cancers Severe hypersensitivity reactions to anti-FGFR2 agents either now or in the past Patients with endocrine metabolic syndrome or history of calcium-phosphate homeostasis Patients with ectopic neoplasm or history of soft tissue, kidney, large intestine, heart, or abdomen Corneal lesions such as bullous keratopathy, corneal erosion, corneal erosion, corneal ulcer, corneal inflammation and keratoconjunctivitis were confirmed by ophthalmic examination Patients with metastasis to the brain or meninges. However, patients who do not have symptoms and do not need treatment can register. Clinically significant digestive system problems that can cause abnormalities in taking or absorbing clinical drugs Patients with uncontrollable or significant cardiovascular disease Patients with systemic infections requiring treatment Patients who were exposed to paclitaxel at or before the taxane If you undergo major surgery within 28 days before enrollment for this trial Patients who received radiotherapy for gastric cancer within 28 days prior to enrollment for this trial. However, the investigation of bone turnover was conducted within 14 days before the registration for this trial If you received general chemotherapy within 14 days of enrollment for this trial Patients who are positive for human immunodeficiency virus (HIV-1) antibody test, HBsAg results positive, HBV viral load greater than 2000 IU / ml (104 copies / ml), or HCV antibody test positive Patients who are pregnant, lactating, or are likely to be pregnant Anemia and hair loss are excluded if previous chemotherapy treatment has toxicity that is not recovered below grade 2. Patients who are judged to have lost their ability to cope with dementia or other comorbid conditions Other Patients who the examiner or the examiner deemed inappropriate for the clinical trial.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

SUN YOUNG RHA

Phone

82-2-2228-8053

rha7655@yuhs.ac

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

SUN YOUNG RHA

Organizational Affiliation

Yonsei Cancer Center, Yonsei University College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yonsei University Health System, Severance Hospital

City

Seoul

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

SUN YOUNG RHA

Phone

82-2-2228-8053,

rha7655@yuhs.ac

12. IPD Sharing Statement

Plan to Share IPD

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