Thalidomide Combined With Chemotherapy and Monotherapy for Maintenance Treatment for Her2-negative Advanced GC

Phase 1

Not yet recruiting

• Conditions: Gastric Cancer Metastatic to Liver
• Interventions: Drug: Thalidomide Combined With Chemotherapy and Monotherapy

• Registration Number: NCT05198856
• Lead Sponsor: Qilu Hospital of Shandong University

Brief Summary

The overall incidence of liver metastases from gastric cancer is about 9.9%-18.7%. Gastric cancer has strong heterogeneity and rapid disease progression, and the prognosis of liver metastasis is poor. The 5-year survival rate of patients with liver metastases from gastric cancer is very low, making clinical treatment challenging.

Thalidomide has immunomodulatory and anti-angiogenesis effects. It has been used in the treatment of multiple myeloma for more than 20 years, and there are many clinical studies in solid tumors. In recent years, thalidomide has been found to induce the degradation of IKAROS family transcription factors IKZF1 and IKZF3 in combination with CRBN. Therefore, it is very meaningful to explore the therapeutic value of thalidomide in advanced gastric cancer liver metastasis.

Detailed Description

The overall incidence of liver metastases from gastric cancer is about 9.9%-18.7%. Gastric cancer has strong heterogeneity and rapid disease progression, and the prognosis of liver metastasis is poor. The 5-year survival rate of patients with liver metastases from gastric cancer is very low, making clinical treatment challenging. Although immune checkpoint inhibitors have been approved for third-line treatment of advanced gastric cancer, they are expensive and poorly accessible. For patients with poor economic conditions, combination therapy based on chemotherapy regimen or treatment regimen optimization may still be a relatively important direction.

Thalidomide has immunomodulatory and anti-angiogenesis effects. It has been used in the treatment of multiple myeloma for more than 20 years, and there are many clinical studies in solid tumors. In recent years, thalidomide has been found to induce the degradation of IKAROS family transcription factors IKZF1 and IKZF3 in combination with CRBN.

In addition, the sedative effect of thalidomide helps to improve patients' sleep. Thalidomide can also inhibit inflammatory factors such as TNF-α, thus improving appetite and increasing lean body weight in patients with cachexia. Its antiemetic effects can reduce gastrointestinal reactions to chemotherapeutic drugs in combined therapy. Thalidomide is also very cheap in China, which is suitable for patients on long-term maintenance treatment. Therefore, it is of great significance to explore the therapeutic value of thalidomide in liver metastasis of advanced gastric cancer.

Study Timeline

• Status Verified: 2021-09
• Study First Submitted: 2021-11-18
• Study First Submitted QC: 2022-01-17
• Last Update Submitted: 2022-01-17
• Study First Posted: 2022-01-20
• Last Update Posted: 2022-01-20
• Study Start: 2022-03-10
• Primary Completion: 2024-03-10
• Study Completion: 2024-12-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

1. Aged 18-75 years old;
2. ECOG physical status score 0-1 points (within 3 days before starting treatment);
3. Expected survival period ≥ 3 months;
4. Basically normal functions of major organs;
5. Pathologically confirmed metastatic gastric cancer or adenocarcinoma at the gastroesophageal junction with no chance of radical surgery, accompanied by liver metastasis or simple liver metastasis;
6. No previous medical treatment; If neoadjuvant or adjuvant chemotherapy has been performed before and after surgery, recurrence can be defined as first-line therapy only after drug withdrawal for at least six months;
7. HER2 negative. HER2 negative definition: IHC (0 or 1+), or IHC (2+) but negative for FISH (HER2:CEP17<2 with mean HER2 copy number <4.0 signals/cell);
8. Measurable lesions assessed according to RECIST1.1;
9. Able to swallow pills normally.

Exclusion Criteria

1. Those who are allergic to thalidomide;
2. Pregnant or lactating women;
3. Severe mental illness;
4. Those who cannot take medication or follow up as planned;
5. During the trial period and within 3 months after the trial, the subjects and their partners are not willing to use contraception;
6. Participants in other clinical studies 3 months prior to the trial；
7. Patients who are financially well off and willing to use immune checkpoint inhibitors.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Thalidomide	Thalidomide Combined With Chemotherapy and Monotherapy	The study is divided into two phases: The first phase is a combination phase (chemotherapy +T) : Oxaliplatin (130mg/m2 iv d1) and capecitabine (1000mg/m2 d1-14 po bid) repeated every 21 days for a total of 4-6 cycles. Thalidomide tablet: 100 mg/d, qn, orally. The second stage is maintenance stage: Patients who have obtained CR, PR or SD in the first stage enter the maintenance stage and receive maintenance treatment with thalidomide tablets: 100mg/d, qn, orally. Maintained until disease progression or adverse reactions are intolerable.

Primary Outcome Measures

Name	Time	Method
progression-free survival (PFS)	Randomization to the first occurrence of disease progression or death from any cause up to the clinical cut off date of March10,2024 (up to approximately 18 months) ]	PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).

Secondary Outcome Measures

Name	Time	Method
Quality of life (QOL)	UpUp to end of study (up to approximately 24 months)	EORTC QLQ-C30 (Version 3) Quality of life questionnaire will be used to assess the quality of life of the subjects.
Percentage of Participants With Adverse Events (AEs)	Up to end of study (up to approximately 24 months)	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.