Trastuzumab + Pertuzumab vs. Cetuximab + Irinotecan for Colorectal Cancer

Not currently recruiting at 815 trial locations

Overseen By Christy Klepetko

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Southwest Oncology Group

Must not be taking: Cetuximab, Panitumumab, EGFR inhibitors

Disqualifiers: Diabetes, Hypertension, Heart failure, 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: 22

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatment combinations to determine which is more effective for colorectal cancer that is HER2/neu amplified and has metastasized. One group will receive trastuzumab and pertuzumab, while the other will receive cetuximab (also known as Erbitux) and irinotecan. Participants should have colorectal cancer that is inoperable and resistant to prior chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not be planning treatment with other systemic anti-cancer agents that are not part of the study.

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

Research has shown that the combination of trastuzumab and pertuzumab is generally well tolerated. In earlier studies, 27 serious side effects were reported among 16 patients, but no new safety issues emerged. Patients did not experience unexpected side effects beyond what was already known.

For the cetuximab and irinotecan combination, studies indicate that 5.7% of patients experienced side effects that led them to stop taking cetuximab, and 10.6% discontinued chemotherapy. However, these side effects were not worse than usual for these drugs. The side effects align with what doctors typically expect from these treatments.

Both treatment options have been studied before, and while side effects can occur, they are generally manageable and known. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for colorectal cancer, which typically include chemotherapy combinations like FOLFOX or FOLFIRI, the investigational treatments in this trial focus on targeted therapy. Pertuzumab and trastuzumab are exciting because they specifically target HER2, a protein that can promote the growth of cancer cells. This is different from traditional chemotherapy, which attacks fast-growing cells indiscriminately. On the other hand, cetuximab and irinotecan work by targeting the epidermal growth factor receptor (EGFR) and interfering with DNA replication in cancer cells. Researchers are excited about these treatments because they offer a more precise approach, potentially improving effectiveness while reducing side effects compared to traditional chemotherapy regimens.

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

This trial will compare two treatment options for colorectal cancer. Research has shown that using trastuzumab and pertuzumab together, which participants in Arm I of this trial may receive, benefits patients with HER2-amplified colorectal cancer. In some studies, nearly half of the patients experienced positive results, with about 30% seeing a reduction in tumor size. This suggests a promising method for targeting HER2 in these cancers.

Participants in Arm II will receive a combination of cetuximab and irinotecan. Studies have found a response rate of over 59% in certain cases, particularly for patients with specific tumor types. This treatment also slows cancer progression. Both treatment options have proven effective, but their success can vary based on individual patient factors. ^{1 2 5 6 7}

Who Is on the Research Team?

Kanwal Raghav

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for adults with HER2/neu amplified colorectal cancer that's spread and can't be surgically removed. They must have had one prior chemotherapy, no severe reactions to the study drugs or similar treatments, no other cancers within two years (except certain skin cancers), and not be pregnant. Participants need a good performance status, adequate organ function, controlled brain metastases if present, and use effective contraception.

Inclusion Criteria

LVEF >= 50% or >= within normal limits for the institution

This is not actually a screening criterion, but a step in the clinical trial process where participants are randomly assigned to different treatment groups.

I've had a full physical exam and shared my medical history within the last 28 days.

Exclusion Criteria

I have received HER-2 targeted therapy for colorectal cancer.

You have had past or current conditions that make you more likely to have an allergic reaction.

My cancer has a specific mutation in the KRAS/NRAS or BRAF gene.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either trastuzumab and pertuzumab or cetuximab and irinotecan hydrochloride. Courses repeat every 21 or 14 days respectively, in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Every 14 or 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 8 weeks after treatment until progression

Crossover (optional)

Patients with documented disease progression may optionally crossover to receive trastuzumab and pertuzumab

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Irinotecan Hydrochloride
• Pertuzumab
• Trastuzumab

Trial Overview The trial compares two treatments: trastuzumab plus pertuzumab versus cetuximab with irinotecan hydrochloride in patients with advanced colorectal cancer. It aims to see which combination is more effective at stopping tumor growth by either killing cancer cells or preventing them from dividing and spreading.

How Is the Trial Designed?

Group I: Arm II (cetuximab, irinotecan hydrochloride) Experimental Treatment 4 Interventions

Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride IV over 90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may optionally crossover to Arm I.

Group II: Arm I (pertuzumab, trastuzumab) Experimental Treatment 4 Interventions

Patients receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30-120 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal 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 post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

In a study of 1147 patients with metastatic colorectal cancer, using a combination of antihistamines and corticosteroids as premedication significantly reduced the incidence of infusion-related reactions (IRRs) from 25.6% to 9.6%.

Despite the reduction in IRRs with combined premedication, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between patients receiving antihistamines with or without corticosteroids, indicating that while safety may improve, efficacy remains similar.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced incidence of infusion-related reactions in metastatic colorectal cancer during treatment with cetuximab plus irinotecan with combined corticosteroid and antihistamine premedication. Siena, S., Glynne-Jones, R., Adenis, A., et al.[2018]

Cetuximab, when combined with irinotecan, can provide patients with metastatic colorectal cancer an additional 1.7 to 2.0 years of life, indicating its efficacy as a treatment option.

However, the cost-effectiveness analysis revealed that the treatment is quite expensive, with costs per life year gained ranging from 205,536 to 323,040 Euros, highlighting the financial considerations of using cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. Norum, J.[2019]

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

In a study of 8 patients with recurrent/advanced colorectal cancer, 6 patients showed a positive response to cetuximab, a targeted therapy that binds to epidermal growth factor receptors (EGFR), indicating its efficacy even in later lines of treatment.

Patients receiving cetuximab in combination with CPT-11 had significantly better progression-free survival (7.3 months) and time to treatment failure (9.3 months) compared to those on cetuximab monotherapy (3.0 months and 4.5 months, respectively), highlighting the potential benefits of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. Katsumoto, Y., Aritake, N., Endoh, A.[2018]

In a multicenter phase II study involving 79 Latin American patients with metastatic colorectal cancer (mCRC) who had previously failed irinotecan treatment, the combination of cetuximab and irinotecan showed an overall response rate of 27% and a disease control rate of 56%.

The treatment was found to be tolerable, with a median overall survival of 9.2 months and a safety profile consistent with previous studies, although 57% of patients experienced grade 3/4 adverse events, primarily skin-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab Plus irinotecan in pretreated metastatic colorectal cancer progressing on irinotecan: the LABEL study. Buzaid, AC., Mathias, Cde C., Perazzo, F., et al.[2018]

In a study involving 65 patients with advanced colorectal cancer who had previously been treated with multiple therapies, the combination of cetuximab and irinotecan showed a response rate of 20% and a median overall survival of 10.4 months, confirming the efficacy of this treatment regimen.

The treatment was associated with low rates of severe toxicity, with only 8% experiencing grade 3 skin toxicity, indicating that cetuximab and irinotecan can be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Pfeiffer, P., Nielsen, D., Yilmaz, M., et al.[2018]

In a study of 56 colorectal cancer patients treated with cetuximab, smokers experienced fewer skin reactions compared to non-smokers, suggesting that smoking may alter the drug's effectiveness.

However, smokers also reported higher rates of anorexia, indicating that while smoking might reduce certain side effects, it could negatively impact overall treatment outcomes, highlighting the importance of quitting smoking during cetuximab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab-induced skin reactions are suppressed by cigarette smoking in patients with advanced colorectal cancer. Kajizono, M., Saito, M., Maeda, M., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3080724/

Cetuximab plus irinotecan in pretreated metastatic ... In a study of cetuximab plus irinotecan, 5-FU, and leucovorin as first-line treatment for mCRC, patients with KRAS wild-type tumors had a response rate of 59.3% ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa0805019

Cetuximab and Chemotherapy as Initial Treatment for ... First-line treatment with cetuximab plus FOLFIRI, as compared with FOLFIRI alone, reduced the risk of progression of metastatic colorectal cancer.

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-13515-3

The impact of combining cetuximab with the ... - BMC Cancer Combining cetuximab with chemotherapy offers a potential benefit in improving survival outcomes for metastatic colorectal cancer patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7270202/

Chemotherapeutic Effectiveness of Combining Cetuximab for ... However, even in patients with left half colorectal cancer where the efficacy of cetuximab is dominant, about 30% of patients have failed (19).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00336856?term=IRINOTECAN&rank=8

Irinotecan and Cetuximab for Colorectal Cancer as Second ... All subsequent treatments will include cetuximab 500 mg/m² IV over 60 minutes and irinotecan 150 mg/m² or 180 mg/m2 intravenously over 60 minutes every 2 weeks.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03290937

Utomilumab, Cetuximab, and Irinotecan Hydrochloride in ... This phase I trial studies the best dose and side effects of irinotecan hydrochloride when given with utomilumab and cetuximab in treating patients with ...

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2005.23.16_suppl.3580

Cetuximab plus irinotecan for metastatic colorectal cancer ... Conclusions: In this pooled analysis the characteristic toxicities of cetuximab and irinotecan do not appear to be increased. The incidence and ...