Chemotherapy + Surgery for Colorectal Cancer

Recruiting at 9 trial locations

Overseen By Mara B. Antonoff, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Regorafenib, Trifluridine/tipiracil

Disqualifiers: Untreated metastases, Intact primary tumor, DPD deficiency, 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 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well chemotherapy and/or metastasectomy work in treating patients with colorectal adenocarcinoma that has spread to the lungs (metastases). Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metastasectomy is a surgical procedure that removes tumors formed from cells that have spread from other places in the body. It is not yet known if chemotherapy and metastasectomy together works better in treating patients with metastatic colorectal adenocarcinoma with lung metastases.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Chemotherapy + Surgery for Colorectal Cancer?

Research shows that new chemotherapy drugs have improved survival rates for patients with metastatic colon cancer. Additionally, combining chemotherapy with surgery has been shown to increase average survival in advanced colorectal cancer. ^{1 2 3 4 5}

Is chemotherapy combined with surgery for colorectal cancer generally safe for humans?

Chemotherapy for colorectal cancer can cause side effects like nausea, vomiting, and skin problems, and may increase risks of heart issues. However, with proper management, these side effects can often be controlled, allowing patients to continue treatment. ^{6 7 8 9 10}

How does the chemotherapy treatment for colorectal cancer differ from other treatments?

This chemotherapy treatment for colorectal cancer is unique because it combines chemotherapy with surgery, which is the standard for patients with metastatic colorectal cancer that can be surgically removed. This approach increases survival rates by using chemotherapy to shrink tumors, making them operable, and then following up with surgery to remove them. ^{11 12 13 14 15}

Research Team

Mara B. Antonoff, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with colorectal adenocarcinoma that has spread to the lungs. Candidates must have good lung function, no severe heart disease, and be able to undergo surgery and chemotherapy. They should not have other untreated cancer sites or a history of certain cancers within 5 years, except some skin or in situ cancers.

Inclusion Criteria

My surgeon agrees I can have surgery to remove lung metastases.

I am using effective birth control during this study.

Ability to provide informed consent for participation

Exclusion Criteria

I cannot tolerate standard treatments for metastatic colorectal cancer.

I have taken regorafenib or TAS-102 for advanced colorectal cancer.

I have not had cancer other than non-dangerous skin cancer or very early stage cancer in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Patients receive standard of care chemotherapy for 3 months

3 months

Metastasectomy

Patients undergo metastasectomy surgery

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Chemotherapy
• Metastasectomy

Trial Overview The study is examining the effectiveness of combining chemotherapy with a surgical procedure called metastasectomy to remove lung tumors in patients whose colorectal cancer has spread there. It's unclear if using both treatments offers better outcomes than one alone.

Participant Groups

Group I: Group 2B (chemotherapy) Experimental Treatment 1 Intervention

High risk patients continue standard of care chemotherapy for 6 months in the absence of disease progression or unacceptable toxicity. Patients with stable disease or radiographic response after 6 months may then cross over to Group 2A.

Group II: Group 2A (metastasectomy) Experimental Treatment 1 Intervention

High risk patients undergo metastasectomy.

Group III: Group 1B (metastasectomy) Experimental Treatment 1 Intervention

Low risk patients undergo metastasectomy.

Group IV: Group 1A (chemotherapy, metastasectomy) Experimental Treatment 2 Interventions

Low risk patients receive standard of care chemotherapy for 3 months prior to and 3 months after undergoing metastasectomy in the absence of disease progression or unacceptable toxicity.

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Recent advancements in colon cancer treatment have significantly improved patient outcomes, primarily due to new chemotherapy agents like irinotecan, oxaliplatin, and capecitabine, as well as biologic agents such as bevacizumab and cetuximab.

Clinical trials have established oxaliplatin/5-FU-based chemotherapy as a new standard for adjuvant therapy in earlier stage colon cancer, with ongoing research exploring the combination of biologic agents and chemotherapy to enhance cure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents, combinations, and opportunities in the treatment of advanced and early-stage colon cancer. Natarajan, N., Shuster, TD.[2006]

Chemotherapy does not extend survival for rectal cancer patients, but it significantly reduces the risk of local recurrence when combined with radiotherapy.

Achieving a complete pathological response (sterilization of the tumor) through chemotherapy is a positive prognostic factor, and new trials are exploring effective drug combinations to enhance these response rates before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy and rectal cancer]. Michel, P., Di Fiore, F.[2018]

5-fluorouracil (5-FU) is the most effective single agent for treating colorectal cancer, but while combination chemotherapy can improve response rates, it generally does not enhance overall survival.

Direct hepatic infusion of chemotherapy shows promise in increasing response rates, but it is still uncertain whether this method improves survival outcomes, highlighting the need for more rigorous trial reporting and evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of chemotherapy in the treatment of colorectal carcinoma. Kemeny, N.[2019]

In patients with KRAS wild-type tumors, combining irinotecan-based chemotherapy with bevacizumab or cetuximab resulted in the longest median overall survival (OS) of 38 and 41 months, respectively, while KRAS-mutated patients had a median OS of 34 months with oxaliplatin-based treatments.

Patients receiving chemotherapy doses below 80% experienced lower overall survival compared to those maintaining doses above 80%, highlighting the importance of dose management in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival and Metastasis Resections in Patients with Metastatic Colorectal Cancer Using Electronic Medical Records. Heervä, E., Lavonius, M., Jaakkola, P., et al.[2018]

The combination of 5-fluorouracil-based regimens with molecularly targeted agents has significantly expanded treatment options for patients with metastatic colorectal cancer, which is crucial given its status as a leading cause of cancer-related death.

Proactive management of adverse events associated with these treatments can lead to uninterrupted therapy and improved quality of life for patients, as the efficacy of the treatment helps prolong wellness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecularly targeted therapy: toxicity and quality of life considerations in advanced colorectal cancer. Ribecco, AS., Pino, MS., Cipriani, G., et al.[2013]

In a study of 46,692 elderly colorectal cancer patients, those receiving intravenous chemotherapy experienced significantly higher rates of adverse events, particularly with oxaliplatin-based regimens, which caused more nausea, neutropenia, and neuropathy compared to fluorouracil alone.

Patients aged 70 and older were more likely to suffer from adverse effects such as infection, anemia, delirium, and heart disease, highlighting the need for careful patient selection and support when administering chemotherapy to older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of toxicity profiles of fluorouracil versus oxaliplatin regimens in a large population-based cohort of elderly patients with colorectal cancer. Cen, P., Liu, C., Du, XL.[2020]

In patients with unresectable RAS wild-type metastatic colorectal cancer, first-line bevacizumab-based chemotherapy significantly reduces the risk of dermatological and renal adverse events, but increases the risk of cardiovascular issues like hypertension and arrhythmia.

Conversely, cetuximab-based chemotherapy is associated with a higher incidence of dermatological and renal adverse events, particularly rashes and electrolyte disorders, highlighting the need for careful selection of targeted therapies based on safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability on Serious Adverse Events of First-Line Bevacizumab and Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Han, YN., Choi, YJ., Rhie, SJ.[2022]

The study assessed the effects of doxorubicin and common chemotherapy drugs on the expression of BCL2 family genes in colorectal cancer cell lines, revealing significant changes in gene expression related to programmed cell death.

Results suggest that BCL2L12 may play a proapoptotic role during chemotherapy treatment, as its expression increases alongside other proapoptotic genes, indicating that these drugs activate the intrinsic apoptotic pathway in colorectal cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Effects of Treatment of Human Colorectal Cancer Cells with Natural and Classical Chemotherapeutic Drugs: Alterations in the Expression of Apoptosis-related BCL2 Family Members, Including BCL2L12. Kontos, CK., Avgeris, M., Vassilacopoulou, D., et al.[2019]

Recent advancements in treatment options for advanced colorectal cancer have significantly improved strategies, moving beyond traditional chemotherapy with 5-fluorouracil to include new cytotoxic drugs like oral fluoropyrimidines, irinotecan, and oxaliplatin.

These new therapies, along with targeted agents, are being integrated into combination protocols, enhancing the potential for long-term survival in patients with metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New chemotherapy approaches in colorectal cancer. Grothey, A., Schmoll, HJ.[2019]

Recent advancements in chemotherapy and biologics have significantly improved treatment outcomes for colorectal cancer (CRC), which remains a leading cause of cancer death, particularly in stage III colon cancer where combination therapy with oxaliplatin is now standard.

The introduction of KRAS mutational status as a predictive marker allows for more personalized treatment approaches in CRC, enhancing the potential for effective management of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Colorectal cancer - personalized, stage-adjusted tumour therapy]. Pohl, M., Schmiegel, W.[2015]

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Role of chemotherapy in the treatment of colorectal carcinoma. [2019]

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Overall Survival and Metastasis Resections in Patients with Metastatic Colorectal Cancer Using Electronic Medical Records. [2018]

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Molecularly targeted therapy: toxicity and quality of life considerations in advanced colorectal cancer. [2013]

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Comparison of toxicity profiles of fluorouracil versus oxaliplatin regimens in a large population-based cohort of elderly patients with colorectal cancer. [2020]

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Tolerability on Serious Adverse Events of First-Line Bevacizumab and Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. [2022]

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Molecular Effects of Treatment of Human Colorectal Cancer Cells with Natural and Classical Chemotherapeutic Drugs: Alterations in the Expression of Apoptosis-related BCL2 Family Members, Including BCL2L12. [2019]

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