Ramucirumab + Chemotherapy for Small Bowel Cancer
Recruiting in Palo Alto (17 mi)
+451 other locations
Overseen byMichael J Overman
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Southwest Oncology Group
Must not be taking: Antiplatelet therapy
Disqualifiers: Irinotecan, Taxane, Ramucirumab, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This phase II trial studies how well ramucirumab and paclitaxel or the FOLFIRI regimen (leucovorin calcium, fluorouracil, and irinotecan hydrochloride) work in treating patients with small bowel cancers that have spread extensively to other anatomic sites (advanced) or are no longer responding to treatment (refractory). Ramucirumab is a monoclonal antibody that attaches to and inhibits a molecule called VEGFR-2. This may restrain new blood vessel formation therefore reducing nutrient supply to tumor which may interfere with tumor cell growth and expansion. Drugs used in chemotherapy, such as paclitaxel, leucovorin calcium, fluorouracil, and irinotecan hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving Ramucirumab plus paclitaxel or FOLFIRI, may be helpful in treating advanced or refractory small bowel cancers and may help patients live longer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot be on chronic antiplatelet therapy like dipyridamole or clopidogrel. You also need to have completed any prior chemotherapy, immunotherapy, or radiation therapy at least 14 days before joining the trial.
What data supports the effectiveness of the drug combination Ramucirumab + Chemotherapy for Small Bowel Cancer?
Research shows that chemotherapy, including drugs like 5-fluorouracil (5-FU) and irinotecan, can help prolong survival in patients with small bowel adenocarcinoma. Additionally, studies on similar drug combinations for colorectal cancer have shown positive responses, suggesting potential benefits for small bowel cancer as well.12345
Is the combination of Ramucirumab and chemotherapy safe for humans?
The combination of chemotherapy drugs like fluorouracil, leucovorin, and irinotecan has been studied for safety in various cancers, showing that they can cause side effects such as diarrhea, myelosuppression (reduced bone marrow activity), and neurotoxicity (nerve damage). However, supportive measures and dose adjustments can help manage these side effects. Ramucirumab, when combined with chemotherapy, has been used in other cancers, but specific safety data for small bowel cancer is not detailed in the provided research.678910
What makes the drug combination of Ramucirumab and chemotherapy unique for small bowel cancer?
This treatment is unique because it combines ramucirumab, a drug that targets blood vessel growth in tumors, with a chemotherapy regimen that includes drugs like fluorouracil and irinotecan, which are typically used for colorectal cancer. This combination may offer a novel approach for small bowel cancer, a condition with limited standard treatment options.45111213
Eligibility Criteria
This trial is for patients with advanced or refractory small bowel adenocarcinoma, excluding ampullary types. Participants must have previously progressed on fluoropyrimidine and/or oxaliplatin treatments, be at least 30 days stable post-brain metastases treatment if applicable, and not have had recent major surgery. They should not be pregnant/nursing, must agree to use contraception if of reproductive potential, and cannot have certain conditions like uncontrolled hypertension or a history of significant thromboembolism.Inclusion Criteria
I have another cancer type, but it won't affect this trial's treatment.
I can carry out all my usual activities without help.
My liver function tests are within the required range.
See 14 more
Exclusion Criteria
Patients must not be currently enrolled in or have discontinued within the last 28 days a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients participating in surveys or observational studies are eligible to participate in this study
My liver functions well, without severe disease or complications like serious fluid buildup.
I have not had a heart attack or stroke in the last 4 months.
See 12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either ramucirumab and paclitaxel or FOLFIRI regimen. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
28 days per cycle
Multiple visits per cycle for IV administration
Follow-up
Participants are monitored every 8 weeks until disease progression, then every 6 months for up to 3 years post registration.
Up to 3 years
Every 8 weeks, then every 6 months
Treatment Details
Interventions
- Fluorouracil (Anti-metabolites)
- Irinotecan (Anti-tumor antibiotic)
- Irinotecan Hydrochloride (Anti-tumor antibiotic)
- Leucovorin (Folate Analog)
- Leucovorin Calcium (Folate Analog)
- Paclitaxel (Taxane)
- Ramucirumab (Monoclonal Antibodies)
Trial OverviewThe study compares the effectiveness of Ramucirumab combined with Paclitaxel versus the FOLFIRI regimen (Fluorouracil, Leucovorin Calcium, Irinotecan Hydrochloride) in treating advanced small bowel cancers. Ramucirumab is an antibody that may inhibit tumor growth by blocking blood vessel formation while other drugs aim to kill or stop cancer cells from dividing.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm II (irinotecan, leucovorin, fluorouracil)Experimental Treatment5 Interventions
Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II: Arm I (ramucirumab, paclitaxel)Experimental Treatment2 Interventions
Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Fluorouracil is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as 5-Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
- Skin cancer
🇪🇺 Approved in European Union as 5-Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
🇨🇦 Approved in Canada as 5-Fluorouracil for:
- Colorectal cancer
- Breast cancer
- Stomach cancer
- Pancreatic cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
IHA Hematology Oncology Consultants-BrightonBrighton, MI
Saint Mary Mercy HospitalLivonia, MI
IHA Hematology Oncology Consultants-Ann ArborYpsilanti, MI
21st Century Oncology-Vegas TenayaLas Vegas, NV
More Trial Locations
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Who Is Running the Clinical Trial?
Southwest Oncology GroupLead Sponsor
SWOG Cancer Research NetworkLead Sponsor
National Cancer Institute (NCI)Collaborator
References
European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. [2018]Tremendous progress has been made in the medical treatment of advanced colorectal cancer during the past 2 to 3 years, due to the availability of several new drugs. Of these new agents, irinotecan (CPT-11 [Camptosar]) seems to be one of the most active against advanced colorectal cancer. It is, therefore, a good candidate for combination with the more classic cytotoxic agents for this disease. This article summarizes several European phase I and II studies in which irinotecan has been combined with (1) fluorouracil (5-FU) alone, given as a repeated bolus injection or a protracted infusion; (2) 5-FU modulated by folinic acid (leucovorin) according to different schedules; or (3) mitomycin (Mutamycin). All of these studies have demonstrated clinical responses in patients with advanced colorectal carcinoma, including complete responses. The toxicity profiles of the various combinations seem to be acceptable; neutropenia and delayed diarrhea are the most frequent side effects. Large phase III studies are still warranted to demonstrate the benefit of these irinotecan-based regimens.
Combination chemotherapy in advanced small bowel adenocarcinoma. [2022]To assess the efficacy of 5-fluorouracil (5-FU) and either platinum compounds or irinotecan in patients with advanced small bowel adenocarcinoma (SBA), for whom data on the efficacy of chemotherapy are scarce.
A phase II study of 5-fluorouracil/L-leucovorin/oxaliplatin (mFOLFOX6) in Japanese patients with metastatic or unresectable small bowel adenocarcinoma. [2022]Several studies have suggested that chemotherapy prolonged survival in patients with metastatic or recurrent small bowel adenocarcinoma (SBA); however, there is still no standard chemotherapy regimen. Here, we evaluated the efficacy and safety of a 5-fluorouracil (5-FU)/L-leucovorin (l-LV)/oxaliplatin (mFOLFOX6) protocol as a first-line therapy for patients with SBA.
Second-line FOLFIRI plus ramucirumab with or without prior bevacizumab for patients with metastatic colorectal cancer. [2023]Few data of folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus ramucirumab (RAM) obtained in bevacizumab-naïve patients in clinical trials or routine clinical practice are available. The purpose of this retrospective study was to report the results of FOLFIRI plus RAM treatment as second-line chemotherapy for metastatic colorectal cancer (mCRC).
Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study. [2019]5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate--leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer.
High vs. low-dose leucovorin in regimens with fluorouracil in colorectal cancer therapy. [2023]The problem of unavailability of drugs and shortages have been a common problem in recent years. Shortages may threaten some treatment regimens for oncological patients. This article presents a systematic review of studies evaluating the efficacy and safety of chemotherapy regimens combining fluorouracil and standard or low-dose leucovorin in treating colorectal cancer. A total of 13 prospective and retrospective studies were included in the review. Meta-analyses and review papers were excluded. It is apparent from the systematic review that a lower dose of leucovorin does not fundamentally affect the efficacy of regimens combining 5-fluorouracil with leucovorin in treating patients with colorectal cancer. Similarly, even in the case of safety, reducing the dose of leucovorin did not influence the frequency and severity of observed adverse effects. Surprisingly, in three studies, some of the adverse effects occurred more often with the higher dose of leucovorin. Furthermore, the article presents the results of a questionnaire survey of the management of leucovorin shortages at the departments of preparation of cytostatics (N = 46) within the Czech Republic. In total, 35 workplaces provided feedback. In 17 cases, the departments for the preparation of cytostatics in the Czech Republic had to accept restrictions on administering the full dose of leucovorin. These restrictions consisted of reducing the dose of the injectable form of leucovorin, changing the chemotherapy regimen, administering the oral form of calcium folinate, forcing a therapeutic break, or a combination of these approaches.
First clinical experience with the magnetic resonance imaging contrast agent and superoxide dismutase mimetic mangafodipir as an adjunct in cancer chemotherapy-a translational study. [2021]Preclinical research suggests that the clinically approved magnetic resonance imaging contrast agent mangafodipir may protect against adverse events (AEs) caused by chemotherapy, without interfering negatively with the anticancer efficacy. The present translational study tested if pretreatment with mangafodipir lowers AEs during curative (adjuvant) FOLFOX6 chemotherapy in stage III colon cancer (Dukes' C). The study was originally scheduled to include 20 patients, but because of the unforeseen withdrawal of mangafodipir from the market, the study had to be closed after 14 patients had been included. The withdrawal of mangafodipir was purely based on commercial considerations from the producer and not on any safety concerns. The patients were treated throughout the first 3 of 12 scheduled cycles. Patients were randomized to a 5-minute infusion of either mangafodipir or placebo (7 in each group). AEs were evaluated according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events and the Sanofi-NCI criteria. The primary end points were neutropenia and neurosensory toxicity. There were four AEs of grade 3 (severe) and one AE of grade 4 (life threatening) in four patients in the placebo group, whereas there were none in the mangafodipir group (P
Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review. [2013]A 43-year-old man with T3 N2 M0 adenocarcinoma of the lower rectum was admitted for preoperative radiochemotherapy (RCT). Daily fractions of 1.8 Gy (planned total dose: 50.4 Gy) and concomitant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, and mitomycin C (MMC) were administered. On day 10, the patient developed abdominal pain and massive diarrhea. Computed tomography, endoscopy, histopathologic and serologic tests revealed severe colitis confined to the upper abdomen and most probably related to 5-FU. Unexpectedly, the bowel inflammation was restricted to areas not irradiated. 4 months later, during the course of disease, relapse with pulmonary metastases occurred. A palliative chemotherapy with 5-FU, oxaliplatin, and leucovorin was started. Again, the patient suffered from severe diarrhea and dose reduction was necessary.
S-1 and irinotecan with or without bevacizumab versus 5-fluorouracil and leucovorin plus oxaliplatin with or without bevacizumab in metastatic colorectal cancer: a pooled analysis of four phase II studies. [2018]S-1, a novel oral prodrug of 5-fluorouracil (5-FU), and irinotecan with or without bevacizumab is known to be effective in metastatic colorectal cancer (mCRC). However, it is not clear whether S-1 and irinotecan confers benefits compared to 5-FU and leucovorin plus oxaliplatin (FOLFOX) in patients with mCRC. Our aim was to compare the efficacy and safety of these regimens.
Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer. [2018]The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in accordance with the increasing concern for the quality of life of patients with cancer. Therapeutic drug monitoring of fluorouracil and chronomodulation of fluorouracil and oxaliplatin, have been effective in reducing the incidence and gravity of adverse effects in several clinical trials. However, these concepts have not been implemented in clinical practice yet. At the present time, dose adaptation and supportive measures are the main tools for toxicity control in the treatment of colorectal cancer. In this review, supportive measures for alleviation of the adverse effects of fluorouracil, raltitrexed, irinotecan and oxaliplatin, respectively, are described, based on study results. The main adverse effects of these agents are myelosuppression, oral mucositis, diarrhoea, acute cholinergic syndrome, nausea and emesis, neurotoxicity, hand-foot syndrome and other cutaneous adverse effects, ocular toxicity, cardiotoxicity, small bowel toxicity, asthenia, elevated liver transaminase levels and alopecia. The incidence and gravity of these adverse effects are more or less related to the agent and administration schedule involved. The supportive measures and recommendations include the use of specific drugs, alterations of administration schedule and several nonpharmacological methods. In addition, guidelines for dosage adjustments when toxicity occurs are presented. For optimal management of adverse effects, patients should be considered individually, while patients, nurses and physicians should cooperate to identify and treat adverse effects in an early stage of their development.
Risk Benefit of FOLFIRI Plus Ramucirumab as Third-line and Later-line Treatment of Metastatic Colorectal Cancer. [2023]The aim of this study was to clarify the risk benefits of folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus ramucirumab (F-RAM) as third-line and later-line treatment for metastatic colorectal cancer (mCRC).
Placental growth factor is a predictive biomarker for ramucirumab treatment in advanced gastric cancer. [2023]Ramucirumab (RAM) has been used as the second-line standard chemotherapy for advanced gastric cancer (AGC) either alone or combination with paclitaxel (PTX). However, no predictive biomarkers have been identified for RAM treatment in AGC.
The safety and efficacy of ramucirumab for the treatment of metastatic colorectal cancer. [2023]Ramucirumab (IMC-1121B, LY3009806) is a fully humanized monoclonal antibody that targets the extracellular domain of vascular endothelial growth factor receptor 2 (VEGFR2), the principal mediator of VEGF-A downstream effects in cancer angiogenesis. Ramucirumab has been recently approved for use in combination with FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed on a first line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. This approval was based on the results of the RAISE phase III placebo-controlled trial. This study demonstrated that the addition of ramucirumab to irinotecan-based chemotherapy significantly improved progression-free and overall survival of patients with mCRC, with manageable toxicity.