Post-Hepatectomy Chemotherapy for Liver Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must be taking: Preoperative chemotherapy
Disqualifiers: Other malignancies, Pregnancy, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
To determine if the detection of ctDNA after surgical resection of CLM can stratify patients into high and low-risk cohorts for early disease recurrence in order to inform post-operative adjuvant therapy.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, since the trial involves chemotherapy, it's best to discuss your current medications with the trial team to ensure there are no interactions.
What evidence supports the effectiveness of the drug combination used in the Post-Hepatectomy Chemotherapy for Liver Cancer trial?
Research shows that chemotherapy using 5-fluorouracil (5-FU) and other drugs like oxaliplatin and irinotecan can improve survival after surgery for liver metastases from colorectal cancer. These drugs are part of the treatment being studied, suggesting potential benefits for liver cancer patients.12345
Is the chemotherapy treatment safe for humans?
How does the post-hepatectomy chemotherapy treatment differ from other treatments for liver cancer?
This treatment is unique because it involves adjuvant chemotherapy, specifically using a regimen like mFOLFOX6, after liver surgery to potentially improve outcomes for liver metastases from colorectal cancer. Unlike standard treatments, it targets the liver directly through intra-arterial infusion, aiming to prevent cancer recurrence in the remaining liver tissue.34111213
Eligibility Criteria
This trial is for adults over 18 with colorectal liver metastases (CLM) who have had or will have their primary cancer removed and plan to undergo surgery with the intent to cure. They must have completed at least 4 cycles of specific preoperative chemotherapy between July 2021 and December 2023. Pregnant women, patients with other active cancers needing treatment, those unable to receive post-surgery chemo, or unwilling/unable to provide blood samples for ctDNA testing are excluded.Inclusion Criteria
I am over 18, have cancer in my liver from another place, and will have surgery to remove it after chemotherapy.
I have completed at least 4 rounds of chemotherapy before surgery.
Exclusion Criteria
I do not have any other cancers needing treatment.
I cannot have or am not planning to have chemotherapy after surgery.
I am currently pregnant.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Surgery
Participants undergo liver resection of colorectal liver metastases with curative intent
1 week
Treatment
Participants receive risk-stratified postoperative chemotherapy based on ctDNA status
6 months
Follow-up
Participants are monitored for recurrence-free survival and overall survival, with ctDNA measurements and adverse event assessments
1 year
Treatment Details
Interventions
- 5-FLUOROURACIL (Anti-metabolites)
- Bevacizumab (Monoclonal Antibodies)
- Capecitabine (Anti-metabolites)
- Irinotecan (Topoisomerase I inhibitors)
- Leucovorin (Anti-metabolites)
- Oxaliplatin (Alkylating agents)
Trial OverviewThe study tests if circulating tumor DNA (ctDNA) can predict early disease recurrence after surgical removal of CLM. It aims to see whether detecting ctDNA helps classify patients into high or low risk for cancer coming back, which could guide further therapy after surgery. Drugs involved include Oxaliplatin, Leucovorin, Fluorouracil (5-FU), Irinotecan, Capecitabine, and Bevacizumab.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: ctDNA (Low Risk)Experimental Treatment2 Interventions
Will receive less intense chemotherapy, such as capecitabine or 5-fluorouracil.
Group II: ctDNA (High Risk)Experimental Treatment6 Interventions
Will receive more intense chemotherapy. This may include resuming the chemotherapy you received before surgery (for example, FOLFOX \[5-fluorouracil, leucovorin and oxaliplatin\] or FOLFIRI \[5-fluorouracil, leucovorin and irinotecan\] with or without bevacizumab)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
[Chemotherapy and hepatectomy for liver metastasis from colorectal cancer]. [2009]Hepatic resection for colorectal liver metastasis remains the only treatment that has curative potential. In half of the patients with recurrences after hepatectomy for liver metastasis, the first site of recurrence is the remnant liver. Furthermore, most patients with recurrence develop metastases. Despite the fact, that adjuvant chemotherapy has been proven very successful in primary colorectal cancer, there is only recent evidence of a benefit after liver surgery. To improve the survival for colorectal liver metastasis, surgery may be combined with adjuvant chemotherapy. In the future, the safety and effectiveness should be determined by clinical trials. The optimal dose, schedule, and combination of oxaliplatin, irinotecan, and fluorouracil plus leucovorin, the presently most effective drugs in colorectal cancer, must be assessed. In this paper, we describe the current status of liver resection and chemotherapy for liver metastasis from colorectal cancer with a review of the literature. Multidisciplinary care and the improved outcomes that are available when we integrate the best of medical and surgical oncology are important.
[Liver metastasis: therapeutic strategy]. [2006]The liver is one of the most frequent sites of metastatic growth, in particular from digestive malignancies (DM). The first goal is to reduce the incidence of metastases. Adjuvant systemic chemotherapies have been demonstrated to reduce the recurrence rate and to improve survival in Dukes C colon cancer. Fluorouracil is the pivot of adjuvant treatment modulated by Leucovorin or Levamisol. A short postoperative administration of fluorouracil by intraportal route has been tested, but the results are controversial. Adjuvant treatments for different DM are under investigation. When hepatic metastases are clinically evident, therapeutic decisions depend on several factors: site and nature of primary, extent of hepatic and extrahepatic disease, patient characteristics, efficacy of treatments. A staging system should be adopted to allow a rational approach. In selected cases a locoregional treatment can achieve consistent results. Hepatic Intrarterial Chemotherapy (HIAC) for colorectal metastases achieves objective responses in more than 50% of patients. Survival seems positively affected. When feasible, Ro hepatic resection is the most effective treatment, five-year survival rate being about 30% when metastases are from colorectal cancer. Since the liver is the most frequent site of recurrence after resection, repeat resection have been successfully performed.
Efficacy of postoperative oxaliplatin- or irinotecan-based chemotherapy after curative resection of synchronous liver metastases from colorectal cancer. [2018]Postoperative 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous liver metastases from colorectal cancer (CRLM). We retrospectively assessed the efficacy of postoperative chemotherapy with a modern regimen containing of oxaliplatin or irinotecan after curative resection of synchronous CRLM.
Hepatectomy Followed by mFOLFOX6 Versus Hepatectomy Alone for Liver-Only Metastatic Colorectal Cancer (JCOG0603): A Phase II or III Randomized Controlled Trial. [2022]Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC.
[Chemotherapy with curative intent before (neoadjuvant) or after (adjuvant) surgery for colorectal cancer liver metastases]. [2007]The 5-year risk of progression after complete resection of liver metastases is of 50% to 75%. Trials which have evaluated adjuvant systemic chemotherapy using 5FU--folinic acid, sometimes in association with intra-arterial chemotherapy, are not powerful and did not demonstrate a clear survival benefit. It is strongly recommended to participate to clinical trials. An adjuvant chemotherapy with the LV5FU2 regimen during 6 months is a reasonable option if the patient has not been included in a trial (professional agreement). A preoperative chemotherapy is not recommended if liver metastases are considered as right away resectable but it should be discussed if resectability is uncertain and/or in case of pejorative factors (professional agreement). If metastases resection has been facilitated or made possible by pre-operative chemotherapy, post-operative resumption of this chemotherapy should also been discussed (professional agreement).
First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study. [2022]The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC).
Dietary glycine protects from chemotherapy-induced hepatotoxicity. [2018]Hepatotoxic side effects of neoadjuvant chemotherapy for colorectal liver metastases increase perioperative morbidity and mortality. Glycine protects liver from injury in various animal models. Thus, this study was designed to assess its effect on liver after chemotherapy. Sprague-Dawley rats (200-220 g) were fed a synthetic diet containing 5% glycine for 5 days. Subsequently, chemotherapy (FOLFIRI: irinotecan, folinic acid and fluorouracil, or FOLFOX: oxaliplatin, folinic acid and fluorouracil) was administered at standard doses. Transaminases, histology, immunohistochemistry and in vivo microscopy were used to index liver injury, to monitor intrahepatic microperfusion and activation of Kupffer cells. Glycine significantly decreased transaminases after chemotherapy to 25-50% of control values (p
Steatohepatitis due to FOLFIRINOX regimen in adjuvant pancreas cancer treatment mimicking liver metastasis. [2020]The combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is more toxic than gemcitabine, but it is a safe regimen with manageable toxicities.
Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. [2022]To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer.
Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]The combination of 5-fluorouracil (5-FU), irinotecan and oxaliplatin (FOLFIRINOX) is considered the first-line chemotherapy for fit patients with advanced pancreatic ductal adenocarcinoma (PDAC) but carries an unfavourable adverse event (AE) profile. We retrospectively evaluated the tolerability and efficacy of a modified FOLFIRINOX (mFOLFIRINOX) regimen: intravenous oxaliplatin 85 mg/m2, irinotecan 135 mg/m2, folinic acid 400 mg/m2 and 5-FU infusion 2,400 mg/m2 over 46 h, with routine subcutaneous filgrastim on a 14-day cycle.
[Prevention of postoperative recurrence after hepatic resection for metastatic colorectal cancer by adjuvant locoregional chemotherapy]. [2013]Postoperative adjuvant locoregional chemotherapy was performed on patients who underwent hepatic resection for metastatic colorectal cancer. To prevent recurrence in the residual liver after hepatic resection. 7 patients received intra-hepato-arterial infusion of MMC, 5-fluorouracil (5-FU), doxorubicin + Lipiodol emulsion. Sixteen cases did not receive such treatment. The 1-, 2- and 3-year cumulative disease free rates were 100, 80 and 40% in the patients with this adjuvant chemotherapy, against 61.4, 54.6 and 28.1% in those without this locoregional therapy, respectively. The 1-, 2- and 3-year cumulative survival rates were 100, 100 and 60% in the TAI-E group, and 73.7, 63.3 and 63.3% in the patients without TAI-E, respectively. Postoperative adjuvant locoregional chemotherapy is considered effective to prevent the recurrence of metastatic colorectal cancer in the residual liver after hepatectomy.
Pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil administration after major hepatectomy in a rat model. [2022]Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired drug clearance during liver regeneration. We investigated the pharmacokinetic and toxicodynamic evaluation of 5-fluorouracil (5-FU) during liver regeneration after major hepatectomy in a rat model.
Adjuvant hepatic intra-arterial chemotherapy after potentially curative hepatectomy for liver metastases from colorectal cancer: a pilot study. [2021]The site most at risk of recurrence after hepatectomy is the remaining liver. Therefore a study was conducted of the use of hepatic intra-arterial and oral chemotherapy for colorectal metastases to prevent intrahepatic recurrence. Our regimen consisted of intra-arterial 5-fluorouracil (5-FU), mitomycin C (MMC) and oral 1-hexylcarbamoyl-5-fluorouracil (HCFU). Sixteen patients were treated. Median total dose of 5-FU was 8.1 g, MMC was 43 mg, and HCFU was 54 g, respectively. Median follow-up period was 21 months. The recurrence rate of the remaining liver was 31%. With respect to the number of hepatic metastases, there was no recurrence in patients with a single deposit. On the other hand, the intrahepatic recurrence rate of patients with multiple deposits was 45%. Of six patients with more than five hepatic deposits, however, only one patient had developed recurrent disease in the liver. Chemical sclerosing cholangitis (19%) was the most serious complication. Consequently, we propose that a prospective randomized trial should be carried out to establish the effects of this type of adjuvant chemotherapy to reduce possible recurrences in the remaining liver.