TEW-7197 With Paclitaxel for the Treatment of Metastatic Gastric Cancer

An Open-label, Multicenter Phase Ib/2a Study of TEW-7197 (Vactosertib) Plus Weekly Paclitaxel as Second-line Treatment for Metastatic Gastric Adenocarcinoma

This is an open-label, single arm study evaluating the safety and tolerability of TEW-7197 in combination with paclitaxel in metastatic gastric cancer patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Gastric Cancer
• Intervention / Treatment: Drug: TEW-7197

Detailed Description

In the dose escalation step (phase 1b), 3 subjects are registered for each dose step, and the DLT is evaluated by administering the investigational product for 1 cycle (28 days). However, for reasons other than toxicity related to the test drug, the patient was given a combination of Paclitaxel and TEW-7197 (Vactosertib) during the DLT evaluation period during the first cycle of the planned TEW-7197.

If more than 80% of the administered dose of (Vactosertib) is not administered, the patient will be considered unevaluable for DLT and another patient will be enrolled. At the end of one cycle of each cohort, the SMC decides whether to proceed to the next cohort. After completing the DLT evaluation of the final phase 1 cohort, the recommended dose to proceed in the dose expansion phase (Phase 2a) is determined. For subjects who have completed one cycle (DLT evaluation period), administer the investigational drug at the same dose until disease progression or unacceptable toxicity occurs. Tumor imaging (CT or MRI) for tumor evaluation is performed after screening and C1D1. Assessment every 6 weeks (±2 weeks) and at the end of treatment (EOT/DC). As efficacy evaluation items, PFS, OS, ORR, and DCR are evaluated according to RECIST 1.1, and the amount of change in the biomarker is confirmed.

In the dose expansion phase (phase 2a), 50 patients will be enrolled at the dose determined in the dose escalation phase. Tumor imaging (CT or MRI) for tumor evaluation is evaluated every 6 weeks (±2 weeks) after screening and C1D1, and at the end of treatment (EOT/DC). As validity evaluation items, PFS, OS, ORR, and DCR according to RECIST 1.1 are evaluated, and the amount of change in the biomarker is confirmed.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Anyang-si, Korea, Republic of
    • Hallym University Medical Center
  • Hwasun, Korea, Republic of
    • Hwasun Chunnam university hospital
  • Seoul, Korea, Republic of
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of
    • Gangnam Severance
  • Seoul, Korea, Republic of
    • Gangbuk Samsung Medical Center
  • Seoul, Korea, Republic of
    • Shinchon Severance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women over 19 years of age
2. Patients diagnosed with histologically or cytologically metastatic gastric cancer
3. Patients corresponding to ECOG Performance Status 0

4. The 5-Fluorouracil family (5-Fluorouracil) is the primary treatment for metastatic gastric cancer.

   Patients who received additional Trastuzumab coalescing therapy for Cisplatin (Oxaliplatin) and Platinum (Oxaliplatin) or HER2-positive.

5. Patients with evalable lesions according to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

6. Patients with the following laboratory test values during screening:

   • Bilirubin is not more than 1.5 times the upper limit of normal (ULN)
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) not more than 3 times ULN (if liver metastasis, not more than 5 times ULN)
   • Serum cretin is not more than 1.5 times the ULN
   • Absolute neutrophil count (ANC)가 1,000 cells/µL 이상
   • Platelet count is over 80,000/µL
   • Hemoglobin count 가 9.0 g/dL 이상
7. Patients who voluntarily agreed to participate in the clinical trial after hearing the explanation of this clinical trial.

Exclusion Criteria:

1. Patients with unresolved chronic toxicity of CTC grade 2 or higher in previous chemotherapy
2. Patients who have received chemotherapy or chemotherapy within two weeks prior to screening
3. Patients who have undergone major surgery or radiation treatment within four weeks prior to screening
4. Patients who have received medication for other clinical trials before screening and have less than 5 times the period of this half-life. Patients who are less than two weeks from the date of final administration if the half-life of the previous clinical trial drug is not clear.
5. Patients previously treated with paclitaxel
6. Patients who previously received treatment targeting the TGF-£ signaling pathway
7. Patients who cannot take tablets
8. Patients who are neurologically unstable due to overall metastasis in the central nervous system or who have increased the amount of steroid to alleviate the central nervous system signs within two weeks before screening.

9. If another type of tumor is present, or within three years prior to screening, another tumor is present.

   diagnosed patients (except for single basal cell carcinoma, thyroid cancer and cervical cancer-insitu)

10. Patients with a history of congestive heart failure or myocardial infarction that is not controlled by medication
11. Pregnant women who are positive for pregnancy test results in this clinical trial and contraception by themselves and their partners during the safety follow-up period after treatment (e.g., infertility surgery, intrauterine, oral contraceptives, liver wall contraception, and other hormone delivery systems, creams, jellies, etc.)
12. Patients with evidence of cirrhosis above Child-Pugh B or C. For HBV or HCV-linked chronic hepatitis or cirrhosis Child-Pugh A, it can be registered for clinical trials if the liver function is reliably maintained through medication.
13. Other patients who are deemed unfit to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation of TEW-7197; TEW-7191 will be given twice daily (BID) for 5 days followed by 2 days off with a cycle of 4 weeks	Drug: TEW-7197; TEW-7197 50mg tablets + Paclitaxel 80 mg/m2 D1, 8, 15 q 4 weeks TEW-7197 dose will be determined through this dose escalation study; Other Names: vactosertib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	To define the MTD and determine RP2D	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events assessed by NCI CTCAE v5.0	To evaluate safety profile of TEW-7197 with regards to frequency, type, grade, and seriousness, and causality of treatment-related clinical and laboratory adverse events including, but not limited to, AST, ALT, total bilirubin, serum creatinine, etc.	from screening through study completion (up to 28 days after the last dose of TEW-7197), an average of 1 year.
Overall survival	Overall survival (months, median) defined by RECIST 1.1	every 2 cycles (8 weeks) and end-of-treatment (EOT) time point. EOT is defined as within 7 days from the last dose of study medication by the protocol.
Objective response	Objective response rate (%) defined by RECIST 1.1	every 2 cycles (8 weeks) and end-of-treatment (EOT) time point. EOT is defined as within 7 days from the last dose of study medication by the protocol.
pharmacokinetics of TEW-7197	Peak Plasma Concentration (Cmax) of TEW-7197 Area under the plasma concentration versus time curve (AUC) of TEW-7197	At cycle 1 (each cycle is 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
pSMAD as a pharmacodynamic marker	pSMAD in peripheral blood mononuclear cell determined by immunohistochemistry	At baseline and cycle 1 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: MedPacto, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2018
• Primary Completion (Anticipated): December 20, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: MP-GC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No