CAPOX + Bevacizumab + Trastuzumab for Stomach Cancer

No longer 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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for stomach cancer that has spread and cannot be surgically removed. It combines chemotherapy (capecitabine and oxaliplatin) with two antibodies, bevacizumab (also known as Avastin) and trastuzumab, to evaluate their safety and effectiveness together. Bevacizumab reduces the blood supply to tumors, while trastuzumab targets cells with a specific protein (HER2) that promotes cancer growth. Suitable participants have HER2-positive stomach cancer that has spread and have not previously received these specific drugs. As a Phase 2 trial, the 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 warfarin or any investigational drugs. You can use low molecular weight heparin for anticoagulation.

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

Research has shown that the combination of capecitabine, oxaliplatin, trastuzumab, and bevacizumab has been tested for safety in individuals with HER2-positive stomach and esophageal cancers. Studies found that this combination is effective against these cancers.

Regarding safety, previous patients tolerated this combination fairly well. Like most cancer treatments, some side effects occurred, but they were usually manageable. Reports from past trials indicated that adding bevacizumab, which reduces the blood supply to tumors, did not significantly increase severe side effects.

These treatments are often used for other conditions, supporting their general safety. While side effects can occur, past research has shown that this treatment combination is generally safe for eligible participants in these types of trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for HER2-positive metastatic esophagogastric cancer because it brings together several powerful agents that work in harmony. Unlike typical chemotherapy regimens, this approach combines Trastuzumab and Bevacizumab, which specifically target and block growth signals in cancer cells. This is coupled with Oxaliplatin and Capecitabine, which damage cancer cell DNA and inhibit cell division. The synergy between these targeted therapies and traditional chemotherapy has the potential to enhance treatment effectiveness while potentially reducing side effects, offering new hope for patients with this aggressive cancer type.

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

This trial will evaluate the effectiveness of a combination of four drugs—trastuzumab, bevacizumab, oxaliplatin, and capecitabine—in treating HER2-positive stomach cancer. Studies have shown that this combination effectively combats stomach cancer. Trastuzumab targets and attacks a protein called HER2 in cancer cells, helping to stop their growth. Bevacizumab cuts off the blood supply to the tumor, limiting its growth. Together with the chemotherapy drugs oxaliplatin and capecitabine, they form a strong team to fight the cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Peter Enzinger

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01191697

CAPOX, Bevacizumab and Trastuzumab for Patients With ... The purpose of this study is to determine the safety and effectiveness of a combination of chemotherapy, capecitabine and oxaliplatin, plus the antibodies ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4843742/

A Retrospective Analysis for Patients with HER2-Positive ... Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. Results. A total of 168 Asian ...

3. nature.com nature.com/articles/s41467-024-51271-3

Clinical outcomes and ctDNA correlates for CAPOX BETR Capecitabine, oxaliplatin, trastuzumab and bevacizumab shows robust clinical activity in HER2+ gastroesophageal adenocarcinoma.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16021

Updated results of HLX22 plus trastuzumab and XELOX for ... Survival outcomes with combined treatment of trastuzumab and chemotherapy remain unsatisfactory. This phase 2 study is evaluating HLX22 and ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39122726/

Clinical outcomes and ctDNA correlates for CAPOX BETR Capecitabine, oxaliplatin, trastuzumab and bevacizumab shows robust clinical activity in HER2+ gastroesophageal adenocarcinoma. Combination ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11316091/

Clinical outcomes and ctDNA correlates for CAPOX BETR Capecitabine, oxaliplatin, trastuzumab and bevacizumab shows robust clinical activity in HER2+ gastroesophageal adenocarcinoma. Combination of ...

7. dana-farber.org dana-farber.org/newsroom/news-releases/2023/clinical-trial-shows-that-adding-bevacizumab-to-targeted-drug-and-chemotherapy-produces-striking-activity-against-her2-positive-metastatic-gastroesophageal-adenocarcinoma

Clinical trial shows that adding Bevacizumab to targeted ... A clinical trial found that a combination of the anti-angiogenic drug bevacizumab, chemotherapy, and a HER2-targeted agent had impressive clinical activity.

8. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT155/725484/Abstract-CT155-Long-term-results-and-ctDNA

Abstract CT155: Long term results and ctDNA correlatives for ... The combination of CAPOX, trastuzumab and bevacizumab shows striking clinical activity comparable to novel triplet regimens that include PD1 blockade for HER2+ ...