Metronomic Gemcitabine, Mitomycin C, and Thalidomide for Advanced Solid Tumors

Official title

GEMINI: Phase II Study Using Metronomic Gemcitabine, Mitomycin C, and Thalidomide for Advanced Solid Tumors

Overview

This is an open label phase II study using metronomic low-dose gemcitabine and mitomycin c given intravenously, and thalidomide administered orally, for patients with advanced solid tumors.

Detailed description

This Phase II open-label single-site study will evaluate the safety and efficacy of metronomic low dose (MLD) therapy with gemcitabine, mitomycin c, and thalidomide in approximately 40-60 patients with pathologically confirmed advanced solid tumors. Patients will receive gemcitabine 600 mg/m2 (Max: 1000 mg) i.v. on D1, D8, D15; Mitomycin C 14 mg i.v. every 6 weeks; and Thalidomide 100 mg p.o. daily x 15 days. CT scan or MRI will be done every 6 weeks for 6 months and every 12 weeks thereafter until disease progression or unacceptable toxicity up to one year of treatment.

Interventions

• Drug Gemcitabine
  600 mg/m2 (Max: 1000 mg) i.v. on D1, D8, D15
• Drug Mitomycin C
  Mitomycin C 14 mg i.v. every 6 weeks
• Drug Thalidomide
  Thalidomide 100 mg daily x 15 days

Primary outcome measures

• Progression Free Survival (PFS) [Time frame: 12 months]

Secondary outcome measures (4)

• Objective Response Rate (ORR) [Time frame: 12 months]
• Progression Free Survival at 6 and 12 months [Time frame: 6 months; 12 months]
• Overall Survival at 6, 12, 24 months [Time frame: 6 months; 12 months; 24 months]
• Adverse Events [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Male or Female ≥ 18 years of age
• Pathologically confirmed diagnosis of locally advanced or metastatic solid tumor
• Previously treated participants
• Measurable disease by RECIST v1.1
• ECOG performance status ≤ 1
• Life expectancy of at least 3 months
• Acceptable liver function: Bilirubin ≤ 1.5 times upper limit of normal (ULN; except subjects with Gilbert Syndrome who must have a total bilirubin level < 3.0 ULN); AST (SGOT), ALT (SGPT) and alkaline phosphatase ≤ 3 x ULN (< 5 x ULN if liver metastases); Acceptable renal function: Creatinine < 1.5 times ULN
• Acceptable hematologic status (without hematologic support e.g. growth factors or transfusion within 21 days of first dose of study agents): ANC ≥ 1500 cells/μL; Platelet count ≥ 100,000/μL; Hemoglobin ≥ 9.0 g/dL; Normal PT, PTT, INR
• All women of childbearing potential must have a negative pregnancy test and all subjects must agree to use highly effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 5 months for women and 7 months for men after the last dose.
• Females of reproductive potential must have 2 negative pregnancy tests before initiating THALOMID. The first test should be performed within 10-14 days, and the second test within 24 hours prior to prescribing THALOMID. Once treatment has started and during dose interruptions, pregnancy testing for females of reproductive potential should occur weekly during the first 4 weeks of use, then pregnancy testing should be repeated every 4 weeks in females with regular menstrual cycles. If menstrual cycles are irregular, the pregnancy testing should occur every 2 weeks. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in her menstrual bleeding. THALOMIDE treatment must be discontinued during this evaluation.
• Ability to understand the purposes and risks of the study and has signed and dated a written informed consent form approved by the principal investigator's IRB/Ethics Committee
• Willingness to comply with all study procedures and availability for the duration of the study.

Exclusion criteria

• Subjects with untreated CNS metastases. Subjects are eligible if CNS metastases have been adequately treated and have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to treatment initiation. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of <10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment initiation.
• Subjects with carcinomatous meningitis
• Subjects who participated in an investigational drug or device study within 14 days prior to study entry
• Subjects who had chemotherapy within 14 days prior to study entry
• Females who are pregnant or breast-feeding
• Unwillingness or inability to comply with the study protocol for any reason
• Evidence of severe or uncontrolled systemic disease or any other concurrent condition, including psychiatric, which in the principal investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the trial
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Sarcoma Oncology Research Center / Cancer Center of Southern California — Santa Monica

Publications

• Shen Y, Li S, Wang X, Wang M, Tian Q, Yang J, Wang J, Wang B, Liu P, Yang J. Tumor vasculature remolding by thalidomide increases delivery and efficacy of cisplatin. J Exp Clin Cancer Res. 2019 Oct 28;38(1):427. doi: 10.1186/s13046-019-1366-x. PMID 31656203
• Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282 (Jun 1958)):457-81.
• Isacoff W.H., Chawla NS, Sekhon S, Bhuiyan I, Monick E, Jeffrey S, Gordon EM. Treatment of Elderly Patients with Advanced Pancreatic Ductal Adenocarcinoma Utilizing a Metronomic Dose and Schedule of Chemotherapy: A Better Approach. Cancers 2025 Preprint doi:10.20944/preprints202510.0364.v1
• Isacoff WH, Cooper B, Bartlett A, McCarthy B, Yu KH. ChemoSensitivity Assay Guided Metronomic Chemotherapy Is Safe and Effective for Treating Advanced Pancreatic Cancer. Cancers (Basel). 2022 Jun 13;14(12):2906. doi: 10.3390/cancers14122906. PMID 35740571
• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026. PMID 19097774
• Liu Q, Chiang ZC, Zhao X, Cui D, Li X, Chen H, Lin F, Jiang T, Chen Q, Lin X, Lin J. Strengthening Effect of Thalidomide Combined with an Anti-PD1 Antibody on Enhancing Immunity for Lung Cancer Therapy. Curr Pharm Biotechnol. 2025;26(17):2724-2737. doi: 10.2174/0113892010319495241218114812. PMID 39773053
• Chen H, Wu S, Tang M, Zhao R, Zhang Q, Dai Z, Gao Y, Yang S, Li Z, Du Y, Yang A, Zhong L, Lu L, Xu L, Shen X, Liu S, Zhong J, Li X, Lu H, Xiong H, Shen Y, Chen H, Gong S, Xue H, Ge Z. Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia. N Engl J Med. 2023 Nov 2;389(18):1649-1659. doi: 10.1056/NEJMoa2303706. PMID 37913505
• Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics. 1982;38:29-41.

Identifiers

NCT: NCT07671534 · SOC-2602

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗