Chemotherapy + Surgery for Colorectal Cancer

Not currently recruiting at 10 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of chemotherapy and surgery in treating colorectal cancer that has spread to the lungs. Chemotherapy uses drugs to stop cancer cells from growing or spreading, while surgery, known as metastasectomy, removes tumors that have spread. The trial compares different combinations of these treatments to determine which works best. It seeks participants with colorectal cancer that has spread to the lungs and who are medically eligible for surgery and chemotherapy. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

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.

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

Research has shown that chemotherapy can cause side effects in patients with colorectal cancer. One study found that 45.7% of patients experienced moderate-to-severe side effects, such as stomach and nerve problems. However, some chemotherapy combinations, like FOLFOX with bevacizumab, are considered safer options.

Metastasectomy, a surgery to remove cancer that has spread to the lungs, is generally well-tolerated. Although studies have not focused extensively on the side effects of this surgery, it is a recognized treatment. This procedure may help improve survival rates in patients with lung metastases from colorectal cancer.

Both chemotherapy and metastasectomy have been used previously and have safety data available. While chemotherapy carries some risks, its safety has been well-studied. Metastasectomy is seen as a safe surgical option aimed at improving long-term outcomes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial because they explore combining chemotherapy with metastasectomy for colorectal cancer in a more tailored way based on patient risk. For low-risk patients, the approach includes standard chemotherapy before and after surgery to remove metastases, which could enhance the effectiveness of surgery by shrinking tumors beforehand and reducing recurrence risk. Meanwhile, high-risk patients may continue chemotherapy alone initially, with the option to undergo surgery later if their disease remains stable, offering a strategic step-up in treatment intensity. This personalized strategy could offer more precise and effective management compared to standard chemotherapy alone, potentially improving outcomes by tailoring treatment intensity to patient risk profiles.

What evidence suggests that chemotherapy and metastasectomy could be effective for metastatic colorectal cancer with lung metastases?

Research has shown that chemotherapy, one of the treatments in this trial, can help treat colorectal cancer. Some studies report that about 34% of patients experience tumor shrinkage or halted growth, with this benefit lasting about 10 months on average. Metastasectomy, another treatment option in this trial, involves surgery to remove tumors that have spread and can significantly improve survival chances. Studies indicate that after surgery to remove lung tumors, survival rates can range from 40% to over 70% over five years. This trial will evaluate the effects of combining chemotherapy with metastasectomy, which might further enhance these outcomes, offering hope for better survival in patients with lung tumors from colorectal cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Mara B. Antonoff, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

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Comparative effectiveness of immunotherapy and ... The treatment of metastatic colorectal cancer poses a significant difficulty in clinical practice, with an overall 5-year survival rate of just 14%[4].

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The efficacy of chemotherapy for colorectal cancer with ... For all patients, the median PFS and OS were 10.4 months and 43.0 months, respectively. The ORR and DCR were 34.4% and 75.0%, respectively. When ...

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Fighting Colorectal Cancer with Immunotherapy: What You ... A novel CAR-T therapy, GCC19CART, recently demonstrated an 80% response rate in a small group of patients with refractory metastatic CRC. As ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2468294224000194

Transforming the landscape of colorectal cancer treatment ... Unfortunately, the 5-year survival rate is approximately only 14 % (13 % for colon and 17 % for rectal cancer). Chemotherapy with or without targeted therapy ...

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Chemotoxicity and Associated Risk Factors in Colorectal Cancer The study found that 45.7% of patients experienced overall moderate-to-severe toxicities, with gastrointestinal toxicity (22.9%) and neuropathy or neutropenia ...

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Safety of first-line systemic therapy in patients with metastatic ... The top three treatment regimens for safety, based on SUCRA values, were FOLFOX + bevacizumab (73.69%), CAPOX + bevacizumab (66.91%), and ...

8. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2022-1284

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Preoperative Chemotherapy for Operable Colon Cancer Six weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy for operable colon cancer can be delivered safely, without increasing perioperative ...

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Therapeutic Characteristics, Chemotherapy-Related ... The 3-year overall survival rate of patients with colorectal cancer was 71%. Median follow-up was 14 months (14–34) with a range of 0– 108 months. Figure 1.