Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00486356
Other study ID # 0284-04-FB
Secondary ID P30CA036727
Status Completed
Phase Phase 1
First received
Last updated
Start date October 1, 2004
Est. completion date January 1, 2010

Study information

Verified date December 2023
Source University of Nebraska
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine, epirubicin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with epirubicin and carboplatin in treating patients with progressive, unresectable, or metastatic cancer.


Description:

OBJECTIVES: Primary - Determine the recommended phase II dose of capecitabine when given together with epirubicin hydrochloride and carboplatin in patients with progressive, unresectable, or metastatic cancer. - Determine the toxicities of this regimen in these patients. Secondary - Correlate end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dose and clinical toxicity in these patients. - Correlate the pharmacokinetics of capecitabine with clinical toxicity in these patients. - Determine the possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity in these patients. - Document antitumor activity of this regimen in these patients. OUTLINE: This is a dose-escalation study of capecitabine. Patients receive epirubicin hydrochloride IV over 2 hours and carboplatin IV over 30 minutes on day 1 and oral capecitabine twice daily on days 2-5, 8-12, and 15-19. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Peripheral blood is collected for pharmacokinetic and pharmacogenetic studies before beginning study treatment and periodically during study. Samples for the pharmacogenetic studies are analyzed for correlation between polymorphisms in the promoter region of the thymidylate synthase gene and clinical toxicity. Patients also undergo bone marrow aspirate before beginning study treatment for molecular profiling studies.


Recruitment information / eligibility

Status Completed
Enrollment 46
Est. completion date January 1, 2010
Est. primary completion date January 1, 2010
Accepts healthy volunteers No
Gender All
Age group 18 Years to 120 Years
Eligibility Inclusion Criteria: - Pathologically confirmed cancer, meeting 1 of the following criteria: - Disease that has progressed on standard therapy - Locally advanced but unresectable primary or recurrent solid tumor - Metastatic disease, including previously untreated metastatic disease for which study regimen represents reasonable initial chemotherapy with palliative intent (e.g., metastatic gastric cancer, hepatobiliary cancer, or cancer for which no effective standard therapy exists) - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Absolute neutrophil count = 2,000/mm³ - Platelet count = 100,000/mm³ - Bilirubin = 1.5 times upper limit of normal (ULN) - alanine aminotransferase (ALT) & aspartate aminotransferase (AST) = 2.5 times ULN - Creatinine = 1.6 mg/dL - Left ventricular ejection fraction = 50% - Fertile patients must use effective contraception - Recovered from prior therapy - More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) or immunotherapy - At least 2 weeks since prior radiotherapy - At least 8 weeks since prior strontium therapy - At least 4 weeks since prior and no concurrent sorivudine or brivudine Exclusion Criteria: - No other potentially curative treatment options available (e.g., surgery, radiotherapy, chemoradiotherapy, or combination chemotherapy) - No leukemia or lymphoma - No primary central nervous system (CNS) malignancies or CNS metastases - No other medical illness that would preclude study treatment - No active infection requiring IV antibiotic therapy unless the infection has resolved - No history of allergy to platinum compounds, mannitol, or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy - No history of unexpectedly severe intolerance to fluorouracil - Not pregnant or nursing/negative pregnancy test - No prior doxorubicin at cumulative doses > 300 mg/m² - No concurrent combination antiretroviral therapy for HIV-positive patients - No concurrent cimetidine

Study Design


Intervention

Drug:
capecitabine

carboplatin

epirubicin hydrochloride

Genetic:
microarray analysis

polymorphism analysis

Other:
pharmacological study


Locations

Country Name City State
United States University of Nebraska Medical Center, Eppley Cancer Center Omaha Nebraska

Sponsors (2)

Lead Sponsor Collaborator
University of Nebraska National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Recommended phase II dose of capecitabine Establish a recommended Phase II dose of oral capecitabine given twice daily on days 2-5, 8-12, and 15-19 in combination with fixed IV doses of epirubicin and carboplatin given day 1 of each 28-day cycle Every 28-days until first documented progression up to 63 months
Primary Toxicities of combined chemotherapy regimen Evaluate all toxicities associated with this combination chemotherapy regimen: 1 - mild, 2 - moderate, 3 = severe and 4 - life-threatening Every 28-days until first documented progression up to 63 months
Secondary End-of-infusion levels of epirubicin hydrochloride/metabolites and incidence of correlation with epirubicin hydrochloride dosing and clinical toxicity Correlation of end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dosing and clinical toxicity (1 - mild, 2 - moderate, 3 = severe and 4 - life-threatening) Each day of dosing up to 63 months
Secondary Correlation of the pharmacokinetics (speed of appearance in the blood plasma and its concentration) of capecitabine with clinical toxicity Measure the pharmacokinetics of capecitabine and correlate these parameters with clinical toxicity Each day of dosing up to 63 months
Secondary Incidence of Correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity Assess possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity Post-treatment up to 63 months
Secondary Antitumor activity Document any anti-tumor activity (MTT assay is a quantitative and sensitive detection of cell proliferation as it measures the growth rate of cells by virtue of a linear relationship between cell activity and absorbance.) Prior to cycle 1, and then every two 28 day cycles up to 63 months
See also
  Status Clinical Trial Phase
Recruiting NCT05551416 - The EpiGASTRIC/EDGAR Project: New Strategies for the Early Detection and Prevention of Gastric Cancer
Completed NCT05518929 - Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients Phase 4
Recruiting NCT06006390 - CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT03219593 - Apatinib as the First-Line Therapy in Elderly Locally Advanced or Metastatic Gastric Cancer Phase 2
Recruiting NCT05489211 - Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03) Phase 2
Recruiting NCT05536102 - The Effectiveness and Safety of XELOX and Tislelizumab + PLD for Resectable Gastric Cancer (LidingStudy) Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Recruiting NCT06010862 - Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors Phase 1
Recruiting NCT05415098 - Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas Phase 1
Active, not recruiting NCT04082364 - Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer Phase 2/Phase 3
Withdrawn NCT03766607 - Trastuzumab Beyond Progression in HER2 Positive Metastatic Gastric Cancer Phase 2
Recruiting NCT04118114 - Phase II Study of PRL3-ZUMAB in Advanced Solid Tumors Phase 2
Completed NCT01924533 - Efficacy and Safety Study of Olaparib in Combination With Paclitaxel to Treat Advanced Gastric Cancer. Phase 3
Terminated NCT01641939 - A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer Phase 2/Phase 3
Recruiting NCT05107674 - A Study of NX-1607 in Adults With Advanced Malignancies Phase 1
Active, not recruiting NCT04908813 - Study of HLX22 in Combanition With Trastuzumab and Chemotherapy Versus Placebo in Combination With Trastuzumab and Chemotherapy for Treatment of Locally Advanced or Metastatic Gastric Cancer Phase 2
Active, not recruiting NCT04249739 - Pembrolizumab + Capecitabine/Oxaliplatin (CapeOx) -HER2 Nagative and Pembrolizumab + Trastuzumab + Cisplatin/Capecitabine HER2 Positive Phase 2
Recruiting NCT05514158 - To Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Disitamab Vedotin Combined With RC98 in the Treatment of Subjects With HER2-expressing Locally Advanced or Metastatic Gastric Cancer (Including AEG) Phase 1
Recruiting NCT04931654 - A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer Phase 1/Phase 2
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2