A Randomized, Multicenter, Open-Label, Phase 2 Study of TRK-950 when Used in Combination with Ramucirumab and Paclitaxel in Patients with Gastric Cancer
A Randomized Phase 2 Study of TRK-950 when Used in Combination with
Ramucirumab and Paclitaxel in Patients with Gastric Cancer
Mori Yoshitaka
Toray Industries, Inc.
10-1, Tebiro 6-chome, Kamakura, Kanagawa
+81-467-32-9948
npdd-clinical.toray.mb@mail.toray
Mori Yoshitaka
Toray Industries, Inc.
10-1, Tebiro 6-chome, Kamakura, Kanagawa
+81-467-32-9948
npdd-clinical.toray.mb@mail.toray
Recruiting
Sept. 01, 2023
Oct. 04, 2023
146
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
- Histologically or cytologically confirmed metastatic, or locally advanced and unresectable gastric or GEJ adenocarcinoma.
- The patient is eligible to receive RAM + PTX.
- Documented objective radiographic or clinical disease progression (e.g., any new or worsening malignant effusion documented by ultrasound examination) which may be confirmed by pathologic criteria (histology and/or cytology) if appropriate, during or after treatment. The prior treatment must meet one of the following criteria with the following treatment history:
a. First treatment for metastatic disease or locally advanced disease without experiencing adjuvant / neo-adjuvant treatment, which progressed during treatment or within 4 months after the last dose of treatment
b. Adjuvant / neo-adjuvant treatment which progressed more than 6 months after the last dose of treatment and first treatment for metastatic disease or locally advanced disease, which progressed during the treatment or within 4 months after the last dose of treatment
c. Adjuvant / neo-adjuvant treatment which progressed during treatment or within 6 months after the last dose of treatment
d. Adjuvant / neo-adjuvant treatment which progressed during treatment or within 6 months after the last dose of treatment and first treatment for metastatic disease or locally advanced disease, which progressed during treatment or within 4 months after the last dose of treatment
- Presence of primary or metastatic disease, measurable per RECIST v1.1 on CT scan.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Life expectancy of at least 3 months.
- Age >= 18 years in the US and Japan, and >= 19 years of age in Korea.
- Signed, written IRB-approved informed consent.
- Adequate organ function from specimens collected within 14 days prior to Day 1.
- For men and women of child-producing potential, the use of effective contraceptive methods during the study and for 6 months after the last dose of TRK-950.
- All patients must sign a pre-screening consent to assess tumor tissue to determine eligibility. Tumor tissue must be evaluable for CAPRIN-1 staining at a CLIA certified laboratory and meet or exceed the cutoff value (30% at >= 2+ staining) as defined in the expression level requirements.
- Prior history of treatment with ramucirumab or paclitaxel.
- HER2 positive gastric or GEJ adenocarcinoma.
- Major surgery within 28 days prior to randomization.
- Baseline corrected QT (QTc) interval of >= 470 msec for females and >= 450 msec for males calculated using Fridericia's formula.
- New York Heart Association (NYHA) Class II - IV symptomatic congestive heart failure, or symptomatic or poorly controlled cardiac arrhythmia.
- The patient has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 3 months prior to randomization.
- The patient has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Clinically symptomatic venous thromboembolism or current treatment with anti-coagulants. (Patients receiving prophylactic and low-dose anticoagulation therapy are eligible provided that the coagulation parameter defined in the Inclusion Criterion 9 is met.)
- Uncontrolled arterial hypertension >= 150 mmHg (systolic) or >= 90 mmHg (diastolic) despite standard medical management.
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
- Pregnant or nursing women.
- Treatment with radiation therapy within 2 weeks, or treatment with chemotherapy, immunotherapy, targeted therapy, or investigational therapy within 4 weeks prior to randomization (within 2 weeks for Oral FU (S1 and capecitabine)).
- The patient has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to randomization.
- Clinically significant ascites, paracentesis in the last 3 months, or undergoes regular paracentesis procedures.
- History of gastrointestinal perforation and/or fistulae within 6 months prior to randomization.
- The patient has a serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to randomization.
- The patient has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (e.g., hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
- Known active infection with HIV, hepatitis B or hepatitis C. Patients with a history of hepatitis B or C are allowed if HBV DNA or Hep C RNA are undetectable.
- The patient is currently enrolled in or discontinued within the last 28 days from a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients who have recently discontinued dosing of study drug are eligible to participate as long as the final dose of study drug was >= 28 days from randomization for participation in this study. Patients participating in surveys or observational studies are eligible to participate in this study.
- Experimental: Arm A: TRK-950(5 mg/kg)+Ramucirumab+Paclitaxel
Participants who will be randomized to receive a 5 mg/kg intravenous(IV) dose of TRK-950 on days 1, 8, 15 and 22 in combination with 8 mg/kg IV dose of ramucirumab on days 1 and 15 and 80 mg/m^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.
- Experimental: Arm B: TRK-950(10 mg/kg)+Ramucirumab+Paclitaxel
Participants who will be randomized to receive a 10 mg/kg IV dose of TRK-950 on days 1, 8, 15 and 22 in combination with 8 mg/kg IV dose of ramucirumab on days 1 and 15 and 80 mg/m^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.
- Active Comparator: Arm C: Ramucirumab+Paclitaxel
Participants who will be randomized to receive a 8 mg/kg IV dose of ramucirumab on Days 1 and 15 in combination with 80 mg/m^2 IV dose of paclitaxel on Days 1, 8, and 15 of a 28-day cycle.
- Progression free Survival (PFS)
Progression free Survival (PFS) is defined as time from the date of randomization to the date of progressive disease or death due to any cause based on Independent Central Review.
- Overall survival (OS)
Overall survival is defined as the time from the date of randomization to the date of death due to any cause.
- Objective response rate (ORR)
Objective response rate (ORR) is defined as the proportion of participants who achieve a best overall response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Independent Central Review.
- Progression free Survival (PFS)
Progression free Survival (PFS) is defined as time from the date of randomization to the date of progressive disease or death due to any cause based on investigator assessment.
- Objective response rate (ORR) Objective response rate (ORR) is defined as the proportion of participants who achieve a best overall response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by investigator.
- Best overall response (BOR)
The best overall response is defined as the best overall response (BOR) recorded from the start of treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Independent Central Review based.
- Best overall response (BOR)
The best overall response is defined as the best overall response (BOR) recorded from the start of treatment until the end of treatment and includes CR, PR, stable disease (SD), progressive disease (PD) and not evaluable (NE) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by investigator.
- Disease control rate (DCR)
Disease control rate (DCR) is defined as the proportion of participants who achieve a best overall response of complete response (CR), partial response (PR) or stable disease (SD) for a minimum of 6 weeks using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Independent Central Review based.
- Disease control rate (DCR)
Disease control rate (DCR) is defined as the proportion of participants who achieve a best overall response of complete response (CR), partial response (PR) or stable disease (SD) for a minimum of 6 weeks using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by investigator.
- Duration of response (DoR)
Duration of response (DoR) is defined as the time from the initial response (CR or PR) until documented tumor progression or death from any cause based on Independent Central Review based.
- Duration of response (DoR)
Duration of response (DoR) is defined as the time from the initial response (CR or PR) until documented tumor progression or death from any cause based on investigator assessment.
- Incidence of Treatment-emergent Adverse Events (TEAE)
Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0.
- Serious Adverse Events (SAEs)
Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0.
- Adverse Events of Special Interest (AESI)
Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0.
- Incidence of Discontinuation due to AE
Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0.
- Incidence of Physical Examination Findings, Vital sign measurements, Standard clinical laboratory parameters, ECG parameters
- Pharmacokinetic Parameter of Concentration of drug at the end of infusion (CEOI), Trough Serum Concentration (Ctrough) and Area Under the Curve (AUC) of TRK-950
- Pharmacokinetic Parameter of Concentration of drug at the end of infusion (CEOI), Trough Serum Concentration (Ctrough) and Area Under the Curve (AUC) of Ramucirumab
- Pharmacokinetic Parameter of Concentration of drug at the end of infusion (CEOI), Trough Serum Concentration (Ctrough) and Area Under the Curve (AUC) of Paclitaxel
- Percentage of participants who are Anti-drug antibody (ADA)-Positive and Neutralizing antibodies (NAbs)
- Patient Reported Quality of Life Outcomes
