Chemotherapy + Bevacizumab for Abdominal Cancer

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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is to test escalating doses of intraperitoneal (IP) oxaliplatin in conjunction with systemic bevacizumab and capecitabine in patients with Peritoneal Carcinomatosis (PC) from either appendiceal or colorectal adenocarcinoma that have been adequately cytoreduced and have undergone a peritoneal scan demonstrating patency of at least one of the intraperitoneal ports that were placed at the time of debulking.

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.

What data supports the effectiveness of the drug combination of Bevacizumab, Capecitabine, and Oxaliplatin for abdominal cancer?

Research shows that adding Bevacizumab to Oxaliplatin-based chemotherapy, like Capecitabine plus Oxaliplatin, is effective in treating metastatic colorectal cancer, which is a type of abdominal cancer. This suggests that the combination could be beneficial for other abdominal cancers as well. ^{1 2 3 4 5}

Is the combination of chemotherapy and Bevacizumab safe for treating abdominal cancer?

Bevacizumab, when used with chemotherapy, has been associated with serious side effects like gastrointestinal perforation, bleeding, and heart problems, but these are generally rare. Common side effects include high blood pressure, protein in urine, and minor bleeding, which are usually manageable. This safety information is based on studies for other cancers, such as lung and colorectal cancer. ^{2 5 6 7 8}

What makes the drug combination of Bevacizumab, Capecitabine, and Intraperitoneal Oxaliplatin unique for abdominal cancer?

This drug combination is unique because it includes Bevacizumab, which blocks the growth of blood vessels that feed tumors, and uses Intraperitoneal Oxaliplatin, which is delivered directly into the abdominal cavity to target cancer cells more effectively. This approach is different from standard treatments that typically use intravenous methods and may not include Bevacizumab. ^{1 2 3 4 9}

Research Team

Benjamin Tan, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

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

Exclusion Criteria

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

I am not pregnant or breastfeeding and will use birth control during the study.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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]

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]

References

1. United States 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. [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

Intraperitoneal and intravenous chemotherapy in peritoneal carcinomatosis. [2022]

3. United States 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. [2023]

4. United States 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. [2021]

5. England 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. [2022]

6. England 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. [2015]

8. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: bevacizumab plus FOLFOX4 as second-line treatment of colorectal cancer. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

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