Cetuximab for Chordoma

Overseen By Anthony Conley, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: EGFR inhibitors

Disqualifiers: Other invasive malignancy, uncontrolled hypertension, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests cetuximab to determine its effectiveness in treating advanced or metastatic chordoma, a rare bone cancer that is difficult to remove surgically. The goal is to assess cetuximab's effectiveness and safety for these patients. Individuals with chordoma that cannot be surgically removed or has spread might be suitable candidates, especially if they have not previously received similar treatments. Participants will receive cetuximab through an IV once a week, provided their condition remains stable and they tolerate the treatment well. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 3 weeks from any systemic therapy (like small molecule/targeted agents or immunotherapies) and/or radiation therapy before starting the study. It does not specify about other medications, so you should discuss your current medications with the study team.

Is there any evidence suggesting that cetuximab is likely to be safe for humans?

Research has shown that cetuximab, a treatment being tested for chordoma, has been studied for safety and tolerability in earlier trials. The FDA has already approved cetuximab for other types of cancer, indicating its safety for humans. Studies have found that most people tolerate cetuximab well, though some may experience side effects like skin reactions or infusion reactions, which are usually manageable. This trial aims to build on existing evidence to evaluate cetuximab's effectiveness specifically in patients with advanced or metastatic chordoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chordoma?

Unlike most treatments for chordoma, which typically involve surgery and radiation, cetuximab offers a different approach by targeting the epidermal growth factor receptor (EGFR), a protein that can promote cancer cell growth. This mechanism of action is unique because it directly interferes with the cancer cells' ability to grow and divide, potentially slowing or stopping tumor progression. Researchers are excited about cetuximab because targeting EGFR could lead to more effective management of chordoma, especially in cases where traditional treatments are not viable or have failed.

What evidence suggests that cetuximab might be an effective treatment for chordoma?

Research shows that cetuximab, the treatment under study in this trial, might help shrink or stop the growth of chordoma tumors, a rare and difficult-to-treat bone cancer. Earlier studies have shown that cetuximab helps the body's immune cells attack these cancer cells. The treatment targets specific proteins on the cancer cells, making it easier for the immune system to find and destroy them. Although detailed data on its effectiveness for chordoma patients is still being collected, early results suggest that cetuximab could be a promising option for those with advanced chordoma or when the cancer has spread to other parts of the body. ^{1 2 4 5 6}

Who Is on the Research Team?

Anthony P. Conley, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic chordoma, a type of cancer. Participants must be at least 18 years old, have a life expectancy over 3 months, and not have used EGFR inhibitors before. They should have measurable disease by scans and good organ function. Women must use effective contraception or be non-childbearing.

Inclusion Criteria

Negative serum pregnancy test for women of childbearing potential

Life expectancy of > 3 months

I can provide samples of my tumor for testing.

Exclusion Criteria

No measurable disease according to RECIST 1.1

History of allergic reactions to compounds similar to cetuximab, red meat allergy, or tick bite history

I have serious heart issues, including recent heart attacks or uncontrolled heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cetuximab IV over 60-120 minutes weekly in the absence of disease progression or unacceptable toxicity

52 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab

Trial Overview The study tests the safety and effectiveness of cetuximab in treating unresectable/metastatic chordoma. It's a phase 2 trial across multiple centers where all participants receive cetuximab. The study includes questionnaires to gather patient-reported outcomes.

How Is the Trial Designed?

Group I: Treatment (cetuximab) Experimental Treatment 2 Interventions

Patients receive cetuximab IV over 60-120 minutes QW 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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 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]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

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 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]

Citations

1. chordomafoundation.org chordomafoundation.org/resources/drug-therapy-options/cetuximab-for-the-treatment-of-advanced-unresectable-or-metastatic-chordoma/

Cetuximab for the Treatment of Advanced… This trial aims to determine whether cetuximab can shrink or stop the growth of chordoma tumors in patients with locally advanced or metastatic disease.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05041127

NCT05041127 | Cetuximab for the Treatment of Advanced ... A Phase II Trial of Cetuximab for Patients With Advanced or Metastatic Chordoma. Conditions. ChordomaMetastatic ChordomaUnresectable Chordoma. Chordoma ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6459012/

A potential therapy for chordoma via antibody-dependent ... These results indicate that haNK cells induce ADCC via cetuximab in chordoma cells. ... Effectiveness of cetuximab/gefitinib in the therapy of a sacral chordoma.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-14259

Cetuximab for the Treatment of Advanced Unresectable or ... This phase II trial studies the effect of cetuximab in treating patients with chordoma that has spread from its original site of growth to distant anatomic ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11522

A phase 1 study of ERAS-601 as a monotherapy ... ... cetuximab in patients (pts) previously treated for advanced chordoma. ... studies with SHP2 inhibitors have demonstrated activity in chordoma ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10741859/

Chordoma: A Comprehensive Systematic Review of Clinical ... This systematic review aims to characterize ongoing clinical trials and therapeutic treatment options for chordoma, a rare notochordal remnant tumor.