Chemotherapy + Cetuximab for Thymic Cancer

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

18 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 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.

What data supports the effectiveness of the drug Cetuximab for treating thymic cancer?

A study showed that Cetuximab, which targets the Epidermal Growth Factor Receptor (EGFR), led to a partial response in two patients with advanced thymic tumors, suggesting it may be a useful treatment option for this condition. ^{1 2 3 4 5}

What is the safety profile of Cetuximab in humans?

Cetuximab is generally considered safe, but it can cause some side effects. The most common side effects include skin rashes that look like acne and mild nail problems. Severe allergic reactions during infusion are rare but can be serious, so patients are monitored closely during treatment. ^{6 7 8 9 10}

How does the drug combination of Chemotherapy + Cetuximab for Thymic Cancer differ from other treatments?

This treatment combines chemotherapy drugs with Cetuximab, a targeted therapy that specifically attacks cancer cells by blocking a protein called EGFR (epidermal growth factor receptor), which is not commonly used in standard thymic cancer treatments. This combination aims to enhance the effectiveness of chemotherapy by adding a targeted approach, potentially offering a novel option for patients with thymic cancer. ^{11 12 13 14 15}

What is the purpose of this trial?

The main purpose of this study is to find out the good and the bad effects that the combination of cetuximab with the traditional chemotherapy regimen of cisplatin, doxorubicin, and cyclophosphamide has when given to patients with later stage thymoma or thymic carcinoma before surgery. The physicians will also look at changes in genes in the tumor that may relate to the effectiveness of cetuximab

Research Team

James Huang, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

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

Epidermal growth factor receptor, C-kit, and Her2/neu immunostaining in advanced or recurrent thymic epithelial neoplasms staged according to the 2004 World Health Organization in patients treated with octreotide and prednisone: an Eastern Cooperative Oncology Group study. [2021]

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

Cetuximab is an active treatment of metastatic and chemorefractory thymoma. [2019]

3. Canada pubmed.ncbi.nlm.nih.gov

Successful Use of Erlotinib in Treating Recurrent Thymic Carcinoma: A Case Report. [2020]

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

[ADOC regimen for unresectable advanced thymic cancer]. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma. [2022]

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

Phase II trial of cetuximab and carboplatin in relapsed platinum-sensitive ovarian cancer and evaluation of epidermal growth factor receptor expression: a Gynecologic Oncology Group study. [2022]

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

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

8. United States 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. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Cetuximab. [2020]

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

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

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

A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy. [2019]

12. England pubmed.ncbi.nlm.nih.gov

R-CHOP versus dose-adjusted R-EPOCH in frontline management of primary mediastinal B-cell lymphoma: a multi-centre analysis. [2019]

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

Prognostic significance of rituximab and radiotherapy for patients with primary mediastinal large B-cell lymphoma receiving doxorubicin-containing chemotherapy. [2019]

14. United States 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. [2022]

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

Antitumor activity of rituximab plus thalidomide in patients with relapsed/refractory mantle cell lymphoma. [2021]