Chemotherapy + Bevacizumab for Abdominal Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Antiretrovirals

Disqualifiers: Pregnancy, Hypersensitivity, Gastrointestinal ailments, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 14 days per cycle, multiple cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a new treatment plan for individuals with abdominal cancers, specifically those originating from the appendix or colon, that have spread to the peritoneum (the lining of the abdominal cavity). It tests different doses of the chemotherapy drug oxaliplatin, administered directly into the abdomen, combined with two other drugs: bevacizumab (also known as Avastin, a type of targeted therapy) and capecitabine. The goal is to determine the safest and most effective dose levels. Individuals who have undergone surgery to remove as much cancer as possible and have working ports for drug delivery in their abdomen might be suitable candidates.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but if you are on antiretroviral therapy for HIV, you cannot participate. It's best to discuss your specific medications with the trial team.

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

Studies have shown that the combination of oxaliplatin, bevacizumab, and capecitabine is generally well-tolerated. Serious side effects, such as severe anemia (a low count of red blood cells), thrombocytopenia (a low count of platelets), and sensory neuropathy (nerve pain), are rare. For most people, these treatments do not cause major problems.

The treatment uses intraperitoneal oxaliplatin, delivering the drug directly into the belly area to target cancer cells more directly. Past research on similar treatments has shown that serious side effects are uncommon.

Bevacizumab and capecitabine are already used in other cancer treatments, indicating a known safety record. While the trial is still in early stages, these treatments have been used safely in the past. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of intraperitoneal oxaliplatin, bevacizumab, and capecitabine for abdominal cancer because of its unique delivery and mechanism. Unlike traditional systemic chemotherapy, intraperitoneal oxaliplatin is delivered directly into the abdominal cavity, potentially increasing concentration at the tumor site while minimizing systemic side effects. Bevacizumab, an antibody that inhibits blood vessel growth, complements this by starving the tumor of nutrients. Lastly, capecitabine is an oral prodrug that turns into 5-FU, enhancing convenience and targeting cancer cells more precisely. This multi-pronged approach could offer more effective and targeted treatment compared to standard chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for peritoneal carcinomatosis?

Research has shown that a combination of three drugs—oxaliplatin, bevacizumab, and capecitabine—may help treat advanced abdominal cancers. This trial will administer different dose levels of this combination to evaluate its effectiveness. Delivering oxaliplatin directly into the abdomen may target tumors more effectively and with fewer side effects. Bevacizumab can stop tumors from growing by preventing the formation of new blood vessels they need. Capecitabine, a chemotherapy pill, helps kill cancer cells. Together, these treatments may offer a comprehensive approach to managing peritoneal cancer originating in the appendix or colon. ^{2 4 5 6 7}

Who Is on the Research Team?

Benjamin Tan, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with peritoneal carcinomatosis from colorectal or appendiceal cancer, who've had debulking surgery and have a working intraperitoneal port. They should be ECOG 0-2, recovered from major illnesses, not pregnant or breastfeeding, and without severe neuropathy or allergies to the drugs tested.

Inclusion Criteria

All patients must be consented prior to chemotherapy. The patient should not have any serious medical of psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment

Hematological Status: absolute neutrophil count ≥1,500/mm³, platelet count ≥100,000/mm³, hemoglobin ≥8 g/dl

I've had at least 4 weeks to recover from major surgery before getting a port for treatment.

Exclusion Criteria

I am not on HAART for HIV due to potential drug interactions.

I do not have any stomach or bowel problems that affect how I absorb pills.

I have moderate to severe numbness, tingling, or pain in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive biweekly intraperitoneal oxaliplatin with systemic capecitabine and bevacizumab

14 days per cycle, multiple cycles

1 visit per cycle (in-person)

Follow-up

Participants are monitored for progression-free survival and progression rate

Estimated 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Capecitabine
• Intraperitoneal Oxaliplatin

Trial Overview The study tests escalating doses of Oxaliplatin given directly into the abdomen in combination with Bevacizumab and Capecitabine taken systemically. It's for patients post-surgery showing clear pathways in their abdominal ports.

How Is the Trial Designed?

Group I: Dose Level 5 Experimental Treatment 3 Interventions

Intraperitoneal oxaliplatin 100 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.

Group II: Dose Level 4 Experimental Treatment 1 Intervention

Intraperitoneal oxaliplatin 85 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.

Group III: Dose Level 3 Experimental Treatment 3 Interventions

Intraperitoneal oxaliplatin 65 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.

Group IV: Dose Level 2 Experimental Treatment 3 Interventions

Intraperitoneal oxaliplatin 50 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.

Group V: Dose Level 1 Experimental Treatment 3 Interventions

Intraperitoneal oxaliplatin 25 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a phase III trial involving 480 patients with metastatic colorectal cancer, maintenance treatment with single-agent bevacizumab showed no significant difference in progression-free survival (PFS) or overall survival (OS) compared to bevacizumab combined with capecitabine and oxaliplatin (XELOX).

The study indicates that while the noninferiority of bevacizumab alone cannot be confirmed, it is a viable maintenance option after initial XELOX plus bevacizumab treatment, with manageable safety profiles including common side effects like diarrhea and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Díaz-Rubio, E., Gómez-España, A., Massutí, B., et al.[2022]

Bevacizumab, when combined with carboplatin and paclitaxel, significantly prolongs progression-free survival in women with newly diagnosed advanced ovarian cancer, as shown in the GOG-0218 and ICON7 studies.

In patients with recurrent platinum-sensitive ovarian cancer, bevacizumab combined with carboplatin and gemcitabine also extends progression-free survival, demonstrating its efficacy in both first-line and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dhillon, S.[2019]

In a study involving 1,401 patients with metastatic colorectal cancer, adding bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 9.4 months compared to placebo.

While overall survival was slightly better in the bevacizumab group (21.3 months vs. 19.9 months), this difference was not statistically significant, and the response rates were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. Saltz, LB., Clarke, S., Díaz-Rubio, E., et al.[2023]

In a study of 1,401 patients with metastatic colorectal cancer, adding bevacizumab to first-line oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 9.4 months compared to placebo.

While overall survival was longer in the bevacizumab group (21.3 months vs. 19.9 months), this difference was not statistically significant, indicating that while bevacizumab helps delay disease progression, it may not necessarily extend overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. Saltz, LB., Clarke, S., Díaz-Rubio, E., et al.[2023]

The combination of docetaxel, oxaliplatin, and bevacizumab as a first-line treatment for advanced ovarian, peritoneal, or fallopian tube cancer showed a promising 12-month progression-free survival rate of 65.7% among 132 patients, with a median progression-free survival of 16.3 months.

The treatment was generally safe, with the most common severe side effects being neutropenia and leukopenia, and only one reported fatal gastrointestinal perforation, indicating no unexpected safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of oxaliplatin, docetaxel, and bevacizumab as first-line therapy of advanced cancer of the ovary, peritoneum, and fallopian tube. Herzog, TJ., Monk, BJ., Rose, PG., et al.[2021]

Bevacizumab (Avastin) combined with carboplatin and paclitaxel significantly improves overall survival in patients with advanced nonsquamous non-small cell lung cancer, with a median survival of 12.3 months compared to 10.3 months for those receiving chemotherapy alone.

While bevacizumab shows efficacy, it is associated with a higher incidence of severe adverse events, including neutropenia and hypertension, and carries risks of serious complications like gastrointestinal perforation and pulmonary hemorrhage, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Cohen, MH., Gootenberg, J., Keegan, P., et al.[2022]

Bevacizumab (Avastin) effectively targets VEGF to inhibit tumor angiogenesis, showing a safety profile that includes mostly mild to moderate side effects such as hypertension and proteinuria, which are manageable in clinical settings.

The side effects associated with bevacizumab, including rare but serious events like gastrointestinal perforation and arterial thrombosis, do not typically exacerbate the toxicity of standard chemotherapy, making it a suitable adjunct treatment for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. Gordon, MS., Cunningham, D.[2015]

Bevacizumab (Avastin) combined with FOLFOX4 significantly improves overall survival and objective response rates in patients with metastatic colon or rectal cancer compared to FOLFOX4 alone, based on a study of 829 patients.

While bevacizumab shows efficacy, it carries risks of serious side effects such as gastrointestinal perforation and hemorrhage, but no new safety concerns were identified in the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer. Cohen, MH., Gootenberg, J., Keegan, P., et al.[2021]

Citations

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NCT01061515 | Biweekly Intraperitoneal Oxaliplatin With ... This study is to test escalating doses of intraperitoneal (IP) oxaliplatin in conjunction with systemic bevacizumab and capecitabine in patients with ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT202383

A phase I dose-escalation trial of intraperitoneal oxaliplatin ... A phase I dose-escalation trial of intraperitoneal oxaliplatin with systemic capecitabine and bevacizumab following cytoreduction in patients with peritoneal ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5551630/

Capecitabine, Oxaliplatin, and Bevacizumab (BCapOx ... Current guidelines recommend BCapOx as first- or second-line therapy for advanced or mCRC and first-line neoadjuvant therapy for colon cancer.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2950329924000092

Emerging therapeutic approaches for peritoneal ... The aim of this review is to provide an overview of the existing and emerging therapies for the peritoneal metastases from gastrointestinal cancers.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2011-01043

Biweekly Intraperitoneal Oxaliplatin with Systemic ... Infusing oxaliplatin directly into the abdomen may kill more tumor cells while reducing side effects. Monoclonal antibodies, such as bevacizumab, can block ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5038216/

Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 ... Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9908703/

Intraperitoneal Chemotherapy for Unresectable Peritoneal ... Outcomes of a phase II Study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases.