Clinical trial NCT06038578: A Study of TRK-950 When Used in Combination With Ramucirumab and Paclitaxel in Patients With Gastric Cancer
Official title: A Randomized, Multicenter, Open-Label, Phase 2 Study of TRK-950 When Used in Combination With Ramucirumab and Paclitaxel in Patients With Gastric Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Adenocarcinoma
Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
Keywords: Gastric Cancer, Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
TRK-950
CAPRIN-1
Lead sponsor: Toray Industries, Inc
Sponsor class: INDUSTRY
First posted: 2023-09-15
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the efficacy, safety, optimal dose and ADA and NAbs development of TRK-950 at two separate dose levels in combination with ramucirumab and paclitaxel (RAM+PTX) as compared with RAM + PTX treatment alone in participants with gastric or gastro-esophageal junction (GEJ) adenocarcinoma.

Detailed description: This study will assess and compare the efficacy, safety, pharmacokinetics (PK), optimal dose and anti-drug antibodies (ADA) and neutralizing antibodies (NAbs) development of TRK-950 at two separate dose levels in combination with RAM + PTX as compared with RAM + PTX treatment alone in participants with gastric or gastro-esophageal junction (GEJ) adenocarcinoma. The primary objective is progression free survival (PFS). Secondary objectives are overall survival, objective response rate, best overall response, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity of TRK-950 when used in combination with RAM+PTX.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed metastatic, or locally advanced and unresectable gastric or GEJ adenocarcinoma.
* The patient is eligible to receive Ramucirumab + Paclitaxel.
* 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:

  1. 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
  2. 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
  3. Adjuvant / neo-adjuvant treatment which progressed during treatment or within 6 months after the last dose of treatment
  4. 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.

Exclusion Criteria:

* 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 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.

Primary outcomes:
measure: Progression free Survival (PFS)
timeFrame: Time from date of randomization to the date of progressive disease or death due to any cause, whichever occurs first, up to approximately 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Time from the date of randomization to the date of death due to any cause, up to approximately 24 months
measure: Objective response rate (ORR)
timeFrame: From start of treatment to date of documented disease progression, up to approximately 24 months
measure: Progression free Survival (PFS)
timeFrame: Time from date of randomization to the date of progressive disease or death due to any cause, whichever occurs first, up to approximately 24 months
measure: Objective response rate (ORR)
timeFrame: From start of treatment to date of documented disease progression, up to approximately 24 months
measure: Best overall response (BOR)
timeFrame: From start of treatment to date of documented disease progression, up to approximately 24 months
measure: Best overall response (BOR)
timeFrame: From start of treatment to date of documented disease progression, up to approximately 24 months
measure: Disease control rate (DCR)
timeFrame: From start of treatment to date of documented disease progression, up to approximately 24 months
measure: Disease control rate (DCR)
timeFrame: From start of treatment to date of documented disease progression, up to approximately 24 months
measure: Duration of response (DoR)
timeFrame: Time from initial response (CR or PR) to date of documented disease progression or death due to any cause, whichever occurs first, up to approximately 24 months
measure: Duration of response (DoR)
timeFrame: Time from initial response (CR or PR) to date of documented disease progression or death due to any cause, whichever occurs first, up to approximately 24 months
measure: Incidence of Treatment-emergent Adverse Events (TEAE)
timeFrame: From time subjects are enrolled up to 45 days after last study dose
measure: Serious Adverse Events (SAEs)
timeFrame: From time subjects are enrolled up to 45 days after last study dose
measure: Adverse Events of Special Interest (AESI)
timeFrame: From time subjects are enrolled up to 45 days after last study dose
measure: Incidence of Discontinuation due to AE
timeFrame: From time subjects are enrolled up to 45 days after last study dose
measure: Incidence of Physical Examination Findings, Vital sign measurements, Standard clinical laboratory parameters, ECG parameters
timeFrame: From time subjects signs informed consent form up to 45 days after last study dose
measure: Pharmacokinetic Parameter of Concentration of drug at the end of infusion (CEOI) of TRK-950
timeFrame: Cycle 1 on day 1 and 15, subsequent cycles on day 1 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Trough Serum Concentration (Ctrough) of TRK-950
timeFrame: Cycle 1 on day 1 and 15, subsequent cycles on day 1 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Area Under the Curve (AUC) of TRK-950
timeFrame: Cycle 1 on day 1 and 15, subsequent cycles on day 1 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Concentration of drug at the end of infusion (CEOI) of Ramucirumab
timeFrame: Cycle 1 and 4 on day 1 and 15, Cycles 2, 3 and subsequent cycles on day 1 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Trough Serum Concentration (Ctrough) of Ramucirumab
timeFrame: Cycle 1 and 4 on day 1 and 15, Cycles 2, 3 and subsequent cycles on day 1 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Area Under the Curve (AUC) of Ramucirumab
timeFrame: Cycle 1 and 4 on day 1 and 15, Cycles 2, 3 and subsequent cycles on day 1 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Concentration of drug at the end of infusion (CEOI) of Paclitaxel
timeFrame: Cycle 1 and 4 on day 1 and 15 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Trough Serum Concentration (Ctrough) of Paclitaxel
timeFrame: Cycle 1 and 4 on day 1 and 15 (each cycle is 28 days)
measure: Pharmacokinetic Parameter of Area Under the Curve (AUC) of Paclitaxel
timeFrame: Cycle 1 and 4 on day 1 and 15 (each cycle is 28 days)
measure: Percentage of participants who are Anti-drug antibody (ADA)-Positive and Neutralizing antibodies (NAbs)
timeFrame: Cycle 1 on day 1 and 15, subsequent cycles on day 1 (each cycle is 28 days)
measure: Change from Baseline in Patient Reported Quality of Life assessed by the Questionnaire - Core questionnaire EORTC QLQ-C30 scores
timeFrame: From Cycle 1 on day 1 through study completion, up to approximately 24 months (each cycle is 28days)
measure: Change from Baseline in Patient Reported Quality of Life assessed by Questionnaire - EuroQOL Five Dimensions questionnaire 3L (EQ-5D-3L) scores
timeFrame: From Cycle 1 on day 1 through study completion, up to approximately 24 months (each cycle is 28days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Irvine
country: United States
facility: City of Hope at Orange County Lennar Foundation Cancer Center
state: California
city: Santa Monica
country: United States
facility: University of California, Los Angeles
state: California
city: Arlington
country: United States
facility: Texas Oncology Arlington North
state: Texas
city: Bedford
country: United States
facility: Texas Oncology Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Dallas Methodist
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Dallas Medical City
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Dallas Presbyterian
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Methodist Charlton Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology Fort Worth Cancer Center
state: Texas
city: Grapevine
country: United States
facility: Texas Oncology Grapevine
state: Texas
city: Plano
country: United States
facility: Texas Oncology Plano East
state: Texas
city: Plano
country: United States
facility: Texas Oncology Plano West
state: Texas
city: Nagaizumi-cho
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
city: Chuo Ku
country: Japan
facility: Osaka International Cancer Institute
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kitaadachi
country: Japan
facility: Saitama Prefectural Hospital Organization Saitama Cancer Center
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Yokohama
country: Japan
facility: Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: