CAPOX + Bevacizumab + Trastuzumab for Stomach Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Warfarin, Investigational agents

Disqualifiers: Active CNS metastasis, Uncontrolled illness, HIV, 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

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

Compensation: Varies

Number of Visits: 1

Duration: Median of 19 cycles (approximately 12 months)

37 Participants Needed

Trial Summary

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 warfarin or any investigational drugs. You can use low molecular weight heparin for anticoagulation.

What data supports the effectiveness of the drug combination CAPOX + Bevacizumab + Trastuzumab for stomach cancer?

Research shows that Trastuzumab, when combined with chemotherapy, improves survival in patients with HER2-positive advanced gastric cancer. Additionally, combining Trastuzumab and Bevacizumab with other chemotherapy drugs has shown promise in treating advanced HER2-positive gastric cancer. ^{1 2 3 4 5}

Is the combination of CAPOX, Bevacizumab, and Trastuzumab safe for treating stomach cancer?

Studies have shown that Trastuzumab combined with chemotherapy is generally safe for patients with advanced gastric cancer, with some experiencing side effects like low white blood cell counts, anemia, and fatigue. These side effects were manageable, indicating that the treatment can be safely administered. ^{1 6 7 8 9}

What makes the CAPOX + Bevacizumab + Trastuzumab drug unique for stomach cancer?

This treatment combines CAPOX (capecitabine and oxaliplatin) with bevacizumab and trastuzumab, targeting HER2-positive stomach cancer by blocking cancer-promoting signals and inhibiting blood vessel growth to the tumor. This combination is unique because it integrates multiple mechanisms of action, potentially offering a more comprehensive approach than standard chemotherapy alone. ^{1 2 5 7 10}

What is the purpose of this trial?

The purpose of this study is to determine the safety and effectiveness of a combination of chemotherapy, capecitabine and oxaliplatin, plus the antibodies bevacizumab and trastuzumab. Trastuzumab (also called Herceptin) is an antibody that attacks HER2 protein in tumor cells. Bevacizumab (also called Avastin) works by slowing or stopping the growth of cells in cancer tumors by decreasing the blood supply of the tumors. If blood supply is decreased, oxygen and nutrients that are needed for tumor growth are decreased. The chemotherapy used in this trial is called CAPOX, which is an abbreviation of capecitabine and oxaliplatin.

Research Team

Peter Enzinger

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with HER2-positive metastatic esophagogastric cancer. Participants must have a tumor sample available, measurable disease, and be in good physical condition (ECOG 0 or 1). They should not have had certain previous cancer treatments and must agree to use contraception. People with serious wounds, recent surgeries, uncontrolled illnesses, known allergies to study drugs or components like Chinese hamster ovary cells are excluded.

Inclusion Criteria

Measurable disease, defined in RECIST 1.1

Life expectancy of greater than 12 weeks

My organs and bone marrow are working well.

Exclusion Criteria

Receiving any concurrent investigational agents

I have received radiation for bone metastasis within the last 2 weeks.

I had minor surgery or a device placed for treatment within the last week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CAPOX chemotherapy, bevacizumab, and trastuzumab in 21-day cycles until disease progression or unacceptable adverse events

Median of 19 cycles (approximately 12 months)

Cycle 1: 1 visit (in-person), Subsequent cycles: 1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Median follow-up of 23.2 months

Treatment Details

Interventions

• Bevacizumab
• Capecitabine
• Oxaliplatin
• Trastuzumab

Trial Overview The trial tests the effectiveness of CAPOX chemotherapy (capecitabine and oxaliplatin) combined with two antibodies: Bevacizumab which cuts off blood supply to tumors; Trastuzumab targeting HER2 protein on tumor cells. The goal is to see if this combination can effectively treat patients.

Participant Groups

Group I: Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine Experimental Treatment 4 Interventions

Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine for patients with HER2-positive metastatic esophagogastric cancer. Each cycle is 21 days. Cycle 1, Day 1 Trastuzumab (loading dose) 4mg/kg IV Cycle 2, Day 1 and all Subsequent Cycles Bevacizumab (7.5mg/kg) IV Trastuzumab (6mg/kg) IV Oxaliplatin (130mg/m2) IV Capecitabine (1200mg/m2) PO (taken Days 1-14 of each cycle) Patients remained on treatment until disease progression, intercurrent illness that prevented further administration of treatment, unacceptable adverse events, participant decision to withdraw consent or general or specific changes in the participant's condition that rendered the participant unacceptable for further treatment.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a study of 44 previously untreated patients with advanced gastric cancer, the combination of cetuximab and XELOX chemotherapy resulted in a significant overall response rate of 52.3%, with median progression-free survival of 6.5 months and overall survival of 11.8 months.

The treatment was generally safe, with most side effects being mild to moderate (grade 1 or 2), such as anemia and asthenia, and serious hematologic toxicities were rare, indicating that cetuximab combined with XELOX is a viable first-line option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Kim, C., Lee, JL., Ryu, MH., et al.[2021]

In a phase IIa study involving 30 patients with advanced gastric cancer, the combination of pertuzumab and trastuzumab showed a well-tolerated safety profile, with partial responses in 86% of patients receiving a specific dosing regimen.

The pharmacokinetics indicated that the serum concentration of pertuzumab was lower in this gastric cancer population compared to those with metastatic breast cancer, leading to the selection of the 840 mg q3w dose for further phase III studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. Kang, YK., Rha, SY., Tassone, P., et al.[2021]

In North America, about 70% of gastric cancer cases are diagnosed at an advanced or metastatic stage, leading to a lower 5-year overall survival rate of around 20%, compared to 40%-60% in Japan.

Trastuzumab, an anti-HER-2 monoclonal antibody, has been shown to improve survival by nearly three months in HER-2 positive advanced gastric cancer patients, making it a viable treatment option when combined with cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of trastuzumab in treatment of advanced stomach cancer. Meza-Junco, J., Au, HJ., Sawyer, MB.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study. [2021]

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

Trastuzumab: a review of its use in HER2-positive advanced gastric cancer. [2021]

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

New developments in the treatment of metastatic gastric cancer: focus on trastuzumab. [2021]

4. Japan pubmed.ncbi.nlm.nih.gov

Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Trastuzumab and bevacizumab combined with docetaxel, oxaliplatin and capecitabine as first-line treatment of advanced HER2-positive gastric cancer: a multicenter phase II study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A phase IIa dose-finding and safety study of first-line pertuzumab in combination with trastuzumab, capecitabine and cisplatin in patients with HER2-positive advanced gastric cancer. [2021]

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

Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer. [2020]

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

Critical appraisal of trastuzumab in treatment of advanced stomach cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Multicenter phase II study of trastuzumab in combination with capecitabine and oxaliplatin for advanced gastric cancer. [2022]