Chemotherapy + Cetuximab for Thymic Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Investigational agents, Antiretrovirals

Disqualifiers: Metastatic disease, Thymic carcinoid, 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: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of cetuximab (a targeted therapy) and traditional chemotherapy drugs for individuals with advanced thymic cancer, a rare chest cancer. The goal is to assess both the beneficial and adverse effects of this treatment before surgery. Researchers will also examine changes in the cancer's genes to evaluate cetuximab's effectiveness. Suitable participants have thymic cancer without prior treatment and have not experienced metastasis. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain investigational agents and medications that alter CYP3A4. It's best to discuss your specific medications with the trial team.

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

Studies have shown that cetuximab, a cancer treatment, can cause skin reactions such as rash and itching in about 25% of patients. Some patients also report changes in their nails. Additionally, around 50% of patients may experience more serious side effects, such as blood clots. Research indicates that cisplatin, a common chemotherapy drug for thymic cancers, is generally well-tolerated but can cause side effects like nausea and kidney problems. Doxorubicin, another chemotherapy drug, is effective for thymic cancer but might lead to heart issues in some patients. Cyclophosphamide, part of a standard chemotherapy mix for thymic cancer, may cause side effects like infertility and an increased risk of other cancers. While these treatments can be effective, they come with potential side effects that should be discussed with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for thymic cancer?

Researchers are excited about this treatment for thymic cancer because it combines cetuximab with chemotherapy agents like cisplatin, doxorubicin, and cyclophosphamide. Unlike standard treatments that typically focus solely on chemotherapy, cetuximab is a monoclonal antibody that specifically targets and blocks the epidermal growth factor receptor (EGFR), which is often overexpressed in thymic tumors. This targeted approach may enhance the effectiveness of traditional chemotherapy by directly interfering with cancer cell growth signals. Additionally, the regimen starts with cetuximab alone to assess tumor response, potentially allowing for more personalized treatment adjustments.

What evidence suggests that this combination treatment could be effective for thymic cancer?

In this trial, participants will receive a combination of cetuximab with the chemotherapy drugs cisplatin, doxorubicin, and cyclophosphamide. Research has shown that combining cetuximab with these chemotherapy drugs may effectively treat thymoma and thymic carcinoma. Specifically, cetuximab has controlled the disease in 79% of thymoma patients, although it is less effective for thymic carcinoma. Chemotherapy with cisplatin, often paired with doxorubicin and cyclophosphamide, can increase the chances of successful surgery and help many patients live longer. The overall success rate for these chemotherapy combinations can reach 70-80%. This suggests that these treatments might help manage the disease and improve outcomes for patients with advanced thymic tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

James Huang, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed or recurrent thymoma or thymic carcinoma, who haven't had previous treatments. They must have a good performance status, normal organ function, and be medically fit for surgery. Pregnant women, HIV-positive patients on certain therapies, and those with other recent cancers or distant metastases cannot participate.

Inclusion Criteria

I am able to care for myself but may not be able to do active work.

My thymoma or thymic carcinoma diagnosis is confirmed by specific cancer centers.

I am fit for surgery.

Exclusion Criteria

I have not had cancer, except for skin cancer or cervical pre-cancer, in the last 5 years.

I am HIV-positive and not on anti-retroviral therapy.

I am taking medications that affect CYP3A4 enzyme activity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cetuximab Monotherapy

Participants receive weekly cetuximab for 4 weeks to assess tumor response

4 weeks

4 visits (in-person)

Chemotherapy and Cetuximab

Participants receive weekly cetuximab along with concurrent CAP (cisplatin, doxorubicin, and cyclophosphamide) for 4 cycles

4 cycles

4 visits (in-person)

Surgical Resection

Participants undergo surgical resection and the specimen is evaluated for CPR

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Cisplatin
• Cyclophosphamide
• Doxorubicin
• Surgical Resection

Trial Overview The study tests the effects of combining cetuximab with traditional chemotherapy (cisplatin, doxorubicin & cyclophosphamide) before surgical removal in advanced stage thymoma or thymic carcinoma patients. It also examines genetic changes in tumors related to cetuximab's effectiveness.

How Is the Trial Designed?

Group I: Cetuximab, Cisplatin, Doxorubicin & Cyclophosphamide Experimental Treatment 1 Intervention

This is a multicenter, open-label phase II trial of neoadjuvant chemotherapy and concurrent cetuximab in patients with clinical Masaoka stage II-IVA thymoma or thymic carcinoma.. Patients will initially receive weekly cetuximab for 4 weeks to assess tumor response to cetuximab alone. Patients will then undergo weekly cetuximab along with concurrent CAP for 4 cycles. At the completion of this regimen, patients will undergo surgical resection and the specimen will be evaluated for CPR.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

City of Hope National Medical Center

Collaborator

Trials

17

Recruited

8,900+

Published Research Related to This Trial

Cetuximab is an effective monoclonal antibody that targets the epidermal growth factor receptor, which is linked to poor outcomes in solid tumors, by blocking its activation and associated oncogenic processes.

While cetuximab can cause infusion reactions and skin-related side effects, its overall safety profile is favorable compared to traditional chemotherapy, and these side effects are generally manageable with appropriate treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: adverse event profile and recommendations for toxicity management. Thomas, M.[2020]

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]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

In a study of 16 patients with relapsed/refractory mantle cell lymphoma, the combination of rituximab and thalidomide resulted in an 81% objective response rate, with 31% achieving complete responses.

The treatment demonstrated a median progression-free survival of 20.4 months and a 3-year survival rate of 75%, indicating significant antitumor activity and a relatively low toxicity profile, although some severe adverse events were noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. Kaufmann, H., Raderer, M., Wöhrer, S., et al.[2021]

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]

Cetuximab (Erbitux) effectively delayed tumor growth in certain xenograft models (GEO and L2987) but showed no significant activity in others (HT29, HCT116, etc.), indicating that not all tumors respond to this treatment despite having detectable EGFR levels.

Combination therapy with cetuximab and cisplatin significantly enhanced efficacy in the GEO model, suggesting that cetuximab may improve the effectiveness of chemotherapy in responsive tumors, while no such enhancement was observed in weakly responsive models like A549.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels. Wild, R., Fager, K., Flefleh, C., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10813974/

What Have We Learned from Molecularly Informed Clinical ... The response rates were 8% and 0% in thymoma and thymic carcinoma patients, respectively, with disease control seen in 79% of thymoma patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6457691/

Chemotherapy for thymic carcinoma and advanced thymoma ... The intended primary outcomes were overall survival (OS) and progression‐free survival (PFS). Data collection and analysis. Two review authors independently ...

3. esmorarecancers.org esmorarecancers.org/article/S3050-4619(25)00023-1/fulltext

Thymic epithelial tumors: what's new and what's next? Figure 3 Outcomes of patients with advanced thymic epithelial tumors (TETs) treated at progression following platinum-based chemotherapy within ...

4. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(07)70141-9/fulltext

Response of thymoma to cetuximab The potential role of EGFR in the pathogenesis of advanced-stage thymomas and the data reported here indicate that developing anti-EGFR antibodies and small ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1556086415326319

Targeted Therapy for Advanced Thymic Tumors In this chapter, we present data from case reports and clinical trials that have explored the role of biologic therapy in thymoma and thymic carcinoma.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf

ERBITUX (cetuximab) - accessdata.fda.gov The most common adverse reactions in ERBITUX clinical trials (incidence ≥25%) include cutaneous adverse reactions. (including rash, pruritus, and nail changes), ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6852841/

Treatment of Advanced Thymoma and Thymic Carcinoma Based on these data, a few case reports have documented clinical responses to treatment with biologic agents like cetuximab [28, 29]. In 2005, Kurup et al. had ...

8. go.drugbank.com go.drugbank.com/drugs/DB00002

Cetuximab: Uses, Interactions, Mechanism of Action Cetuximab is an anticancer agent that works by inhibiting the growth and survival of epidermal growth factor receptor (EGFR)-expressing tumour cells.

9. cancercareontario.ca cancercareontario.ca/en/drugformulary/drugs/monograph/44161

cetuximab However, there does not appear to be any relationship between the appearance of antibodies to cetuximab and the safety or antitumour activity of cetuximab.

10. sciencedirect.com sciencedirect.com/science/article/pii/S3050461925000231

Thymic epithelial tumors: what's new and what's next? Safety was consistent with RELEVENT, with 50% experiencing grade 3 adverse events (AEs) and 1 thromboembolic event, suggesting the possibility of an increased ...