Clinical trial · Interventional

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

A Single-arm, Open, Prospective, Multi-center Study on Thalidomide Combined With First-line Chemotherapy and Monotherapy for Maintenance Treatment of Liver Metastases From Her2-negative Advanced Gastric Cancer

NCT05198856CI-TRIAL-00056055unknownPhase 1 / Phase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Gastric Cancer Metastatic to Liver	Gastric Neoplasm	ALIAS	0.90

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
Thalidomide Combined With Chemotherapy and Monotherapy	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Thalidomide
description
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.
interventionNames
1. Drug: Thalidomide Combined With Chemotherapy and Monotherapy

Primary outcomes (1)

measure
progression-free survival (PFS)
timeFrame
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) ]
description
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).

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 75 Years

Show eligibility criteria text

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.

References

Publications (9)

BACKGROUNDRiihimaki M, Hemminki A, Sundquist K, Sundquist J, Hemminki K. Metastatic spread in patients with gastric cancer. Oncotarget. 2016 Aug 9;7(32):52307-52316. doi: 10.18632/oncotarget.10740. PMID 27447571
BACKGROUNDCheon SH, Rha SY, Jeung HC, Im CK, Kim SH, Kim HR, Ahn JB, Roh JK, Noh SH, Chung HC. Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases. Ann Oncol. 2008 Jun;19(6):1146-53. doi: 10.1093/annonc/mdn026. Epub 2008 Feb 27. PMID 18304963
BACKGROUNDXiao Y, Zhang B, Wu Y. Prognostic analysis and liver metastases relevant factors after gastric and hepatic surgical treatment in gastric cancer patients with metachronous liver metastases: a population-based study. Ir J Med Sci. 2019 May;188(2):415-424. doi: 10.1007/s11845-018-1864-4. Epub 2018 Jul 30. PMID 30062399
BACKGROUNDKang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. doi: 10.1016/S0140-6736(17)31827-5. Epub 2017 Oct 6. PMID 28993052
BACKGROUNDFuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 May 10;4(5):e180013. doi: 10.1001/jamaoncol.2018.0013. Epub 2018 May 10. PMID 29543932