Ramucirumab + Chemotherapy for Small Bowel Cancer

Recruiting at 571 trial locations

Overseen By Dana Sparks

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Southwest Oncology Group

Must not be taking: Antiplatelet therapy

Disqualifiers: Irinotecan, Taxane, Ramucirumab, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 28 days per cycle

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining ramucirumab (a drug that may limit blood flow to tumors) with chemotherapy for advanced or treatment-resistant small bowel cancer. The trial includes two groups: one receives ramucirumab and paclitaxel, while the other receives leucovorin, fluorouracil, and irinotecan. The researchers aim to determine if these treatments can slow cancer growth and potentially extend patients' lives. The trial seeks participants with small bowel adenocarcinoma that has spread or cannot be surgically removed, and who have already tried other treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of ramucirumab and paclitaxel is generally well-tolerated. In studies with patients who have advanced stomach cancer, this combination did not cause any major unexpected side effects. However, like many cancer treatments, some patients experienced side effects, which were usually manageable.

Similarly, the combination of irinotecan, leucovorin, and fluorouracil has been widely studied for advanced colon cancer. Research indicates that this combination can help shrink tumors even when other treatments have stopped working. Side effects are common but can typically be managed with medical support.

Both treatment combinations have demonstrated safety in previous studies, suggesting they are generally safe for use in trials. However, participants might still experience some side effects. Always discuss potential risks with the trial team before deciding to join. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new hope for small bowel cancer, a condition with limited standard care options like surgery and chemotherapy. Ramucirumab, one of the investigational treatments, is unique because it targets the blood vessels that supply the tumor, effectively starving it and inhibiting growth. This mechanism differs from traditional chemotherapy, which primarily targets rapidly dividing cells. Additionally, the combination of ramucirumab with paclitaxel could potentially enhance the effectiveness of treatment by attacking the cancer on multiple fronts. Meanwhile, the other treatment arm uses a well-known chemotherapy regimen of irinotecan, leucovorin, and fluorouracil, but the continuous infusion method aims to improve efficacy and reduce side effects.

What evidence suggests that this trial's treatments could be effective for small bowel cancer?

In this trial, one treatment arm uses ramucirumab with paclitaxel, which research has shown to be effective for treating small bowel cancer. Studies have found that 43.8% of patients experience significant tumor shrinkage, with some achieving complete or partial recovery.

Another treatment arm involves a combination of irinotecan, leucovorin, and fluorouracil, known as FOLFIRI. This combination has proven helpful for similar cancers, such as colorectal cancer. Research consistently shows that FOLFIRI improves survival rates and helps control cancer growth.

Both treatment combinations in this trial slow the spread of cancer by either directly attacking tumor cells or cutting off their nutrient supply. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael J Overman

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Irinotecan
• Irinotecan Hydrochloride
• Leucovorin
• Leucovorin Calcium
• Paclitaxel
• Ramucirumab

Trial Overview The 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.

How Is the Trial Designed?

Group I: Arm II (irinotecan, leucovorin, fluorouracil) Experimental Treatment 5 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 Treatment 2 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

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 20 patients with advanced small bowel adenocarcinoma, chemotherapy combining 5-fluorouracil (5-FU) with platinum compounds showed a 21% overall response rate, with median progression-free survival of 8 months and overall survival of 14 months, indicating moderate efficacy and tolerability.

The combination of 5-FU and irinotecan demonstrated promising results, with 50% of patients achieving disease stabilization and one patient experiencing a complete biological response, suggesting that this combination warrants further investigation as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy in advanced small bowel adenocarcinoma. Locher, C., Malka, D., Boige, V., et al.[2022]

Ramucirumab, a monoclonal antibody targeting VEGFR2, has been approved for use with FOLFIRI in patients with metastatic colorectal cancer (mCRC) who have progressed after initial treatments, showing significant improvements in progression-free and overall survival.

The RAISE phase III trial demonstrated that adding ramucirumab to irinotecan-based chemotherapy resulted in manageable toxicity, indicating it is a safe and effective option for mCRC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of ramucirumab for the treatment of metastatic colorectal cancer. Diaz-Serrano, A., Riesco-Martinez, MC., Garcia-Carbonero, R.[2023]

In a study of 187 patients with metastatic colorectal cancer, the combination of S-1 and irinotecan (with or without bevacizumab) showed similar overall response rates and survival outcomes compared to the standard FOLFOX regimen, indicating comparable efficacy.

S-1 and irinotecan were well tolerated, with gastrointestinal side effects being the most common, while FOLFOX was associated with neutropenia and sensory neuropathy, suggesting a different safety profile for the two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Iwasa, S., Nagashima, K., Yamaguchi, T., et al.[2018]

Chemotherapy agents like fluorouracil and oxaliplatin can cause significant side effects in colorectal cancer treatment, but strategies like therapeutic drug monitoring and chronomodulation have shown promise in reducing these adverse effects in clinical trials.

Supportive measures, including specific medications and schedule adjustments, are essential for managing side effects such as myelosuppression and nausea, emphasizing the need for individualized patient care and teamwork among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer. Jansman, FG., Sleijfer, DT., de Graaf, JC., et al.[2018]

A systematic review of 13 studies found that reducing the dose of leucovorin in chemotherapy regimens combining it with fluorouracil does not significantly impact the efficacy of treatment for colorectal cancer.

Lower doses of leucovorin also do not increase the frequency or severity of adverse effects, and in some cases, higher doses were associated with more side effects, indicating that dose adjustments may be a safe alternative during drug shortages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High vs. low-dose leucovorin in regimens with fluorouracil in colorectal cancer therapy. Juřica, J., Šuverová, P., Goněc, R., et al.[2023]

In a study involving 14 patients with stage III colon cancer undergoing FOLFOX6 chemotherapy, pretreatment with the MRI contrast agent mangafodipir significantly reduced severe adverse events (AEs) compared to a placebo, with no severe AEs reported in the mangafodipir group.

Patients receiving mangafodipir also had a significantly higher white blood cell count after treatment, suggesting that it may help protect against neutropenia, a common side effect of chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First clinical experience with the magnetic resonance imaging contrast agent and superoxide dismutase mimetic mangafodipir as an adjunct in cancer chemotherapy-a translational study. Karlsson, JO., Adolfsson, K., Thelin, B., et al.[2021]

In a case study of a 43-year-old man with rectal adenocarcinoma undergoing preoperative radiochemotherapy, severe colitis was observed, likely related to the chemotherapy drug 5-fluorouracil (5-FU), despite the inflammation being confined to non-irradiated areas.

The authors hypothesized that low-dose radiation may have an anti-inflammatory effect that mitigated 5-FU-induced colitis early in treatment, suggesting the need for careful differentiation between radiation and chemotherapy side effects to optimize individual therapy plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does radiation prevent 5-fluorouracil-induced colitis in the early phase of radiochemotherapy? A case report and literature review. Rischke, HC., Momm, F., Henke, M., et al.[2013]

In a phase II study involving 24 patients with metastatic or recurrent small bowel adenocarcinoma, the mFOLFOX6 chemotherapy regimen demonstrated a 1-year progression-free survival (PFS) rate of 23.3%, indicating some efficacy as a first-line treatment.

The treatment was generally well tolerated, with no treatment-related deaths reported, although significant side effects included neutropenia (38%) and anemia/peripheral neuropathy (25%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of 5-fluorouracil/L-leucovorin/oxaliplatin (mFOLFOX6) in Japanese patients with metastatic or unresectable small bowel adenocarcinoma. Horimatsu, T., Nakayama, N., Moriwaki, T., et al.[2022]

Irinotecan has shown significant activity against advanced colorectal cancer when combined with traditional chemotherapy agents like fluorouracil, leading to clinical responses including complete remissions in patients.

The combination therapies have acceptable toxicity profiles, with neutropenia and delayed diarrhea being the most common side effects, indicating that irinotecan could be a safe option for treatment, although further large-scale phase III studies are needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. Khayat, D., Gil-Delgado, M., Antoine, EC., et al.[2018]

In a study of 74 patients with metastatic colorectal cancer (mCRC) receiving second-line treatment with FOLFIRI plus ramucirumab, the median progression-free survival (PFS) was 6.2 months and median overall survival (OS) was 17.0 months, indicating a significant therapeutic benefit.

Patients who had not previously received bevacizumab (bevacizumab-naïve) showed better treatment responses, with a response rate of 23% and a disease control rate of 85%, compared to only 3% and 69% in those who had received bevacizumab as first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line FOLFIRI plus ramucirumab with or without prior bevacizumab for patients with metastatic colorectal cancer. Suzuki, T., Shinozaki, E., Osumi, H., et al.[2023]

In a phase II study involving 97 patients with metastatic colorectal cancer, the combination of methotrexate, leucovorin, and 5-fluorouracil resulted in a partial or complete response in 31% of patients, with a median response duration of 6.4 months.

The treatment showed a median overall survival of 13 months and a 1-year survival rate of 53.7%, with manageable side effects such as mucositis, nausea, and vomiting, indicating a modest clinical benefit of this chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study. Tomlinson, SK., Melin, SA., Higgs, V., et al.[2019]

In a study comparing FOLFIRI plus ramucirumab (F-RAM) to TAS-102 for treating metastatic colorectal cancer, both treatments showed no significant difference in overall survival, with median survival times of 6.1 months for both groups.

However, F-RAM was associated with more frequent adverse events and significantly higher costs ($81,724.8 for F-RAM vs. $18,931.4 for TAS-102), indicating that TAS-102 is a more favorable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Benefit of FOLFIRI Plus Ramucirumab as Third-line and Later-line Treatment of Metastatic Colorectal Cancer. Kimura, M., Usami, E., Teramachi, H., et al.[2023]

In a study of 26 patients with advanced gastric cancer, high levels of placental growth factor (PlGF) were associated with poor treatment outcomes for ramucirumab (RAM), indicating that PlGF expression could serve as a predictive biomarker for RAM efficacy.

Patients with low PlGF levels had a 50% overall response rate to RAM treatment, while those with high PlGF levels showed no response, suggesting that targeting PlGF may enhance the effectiveness of RAM therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placental growth factor is a predictive biomarker for ramucirumab treatment in advanced gastric cancer. Natsume, M., Shimura, T., Iwasaki, H., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9575722/

The efficacy of irinotecan supplementation for colorectal ... This meta-analysis aims to assess the efficacy and safety of irinotecan in combination with fluorouracil and leucovorin for colorectal cancer.

2. nejm.org nejm.org/doi/full/10.1056/NEJM200009283431302

Irinotecan plus Fluorouracil and Leucovorin for Metastatic ... Weekly treatment with irinotecan plus fluorouracil and leucovorin is superior to a widely used regimen of fluorouracil and leucovorin for metastatic colorectal ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00080951

Irinotecan, Fluorouracil, Leucovorin, and Oxaliplatin as ... PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy as first-line therapy in treating patients who have metastatic colorectal cancer.

4. cancernetwork.com cancernetwork.com/view/irinotecan-and-5-fuleucovorin-metastatic-colorectal-cancer-balancing-efficacy-toxicity-and-logistics

Irinotecan and 5-FU/Leucovorin in Metastatic Colorectal ... The combination of irinotecan with 5-FU/leucovorinhas consistently improved survival and response rates in comparisonto 5-FU/leucovorin alone.

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1356708/full

The effective combination therapies with irinotecan for ... Irinotecan is a critical component of the therapy of CRC and is typically used with other drugs to ease cancer-related symptoms and increase patients' survival ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.195

Liposomal irinotecan + 5-fluorouracil + leucovorin + ... This study aims to investigate the efficacy and safety of liposomal irinotecan in combination with 5-FU/LV and bevacizumab as a second-line treatment option ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC497044/

Irinotecan plus folinic acid/continuous 5-fluorouracil as ... Combination therapy of irinotecan, folinic acid (FA) and 5-fluorouracil (5-FU) has been proven to be highly effective for the treatment of metastatic colorectal ...

8. cancernetwork.com cancernetwork.com/view/irinotecan-plus-5-fu-and-leucovorin-advanced-colorectal-cancer-north-american-trials

Irinotecan Plus 5-FU and Leucovorin in Advanced ... The NCCTG and other trials have clearly shown that some tumors that grow during treatment with 5-FU and leucovorin will shrink when exposed to irinotecan. This ...