Ablative Therapy + Systemic Therapy for Colorectal Cancer

Recruiting at 203 trial locations

Overseen By Aleksandar Jankov

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Disqualifiers: Liver-only metastases, Unresectable primary tumors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Duration: Up to 5 years

364 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding focused treatments, such as intense radiotherapy or heat-based tumor removal (microwave ablation), is more effective than chemotherapy alone for colorectal cancer that has spread to a few locations. The goal is to assess whether these additional treatments can better shrink, remove, or prevent tumors from returning. Ideal participants have colorectal cancer with up to four spread sites and have not shown disease progression during recent systemic therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have been on first-line systemic therapy for at least 16 weeks before joining the trial.

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

Research has shown that the treatments in this trial are safe based on previous studies. Microwave ablation, which uses heat to destroy cancer cells, has proven very successful with few problems. One study found it effective in 94.7% of cases, with only a 3.3% chance of cancer recurrence.

Stereotactic ablative radiotherapy (SABR), a precise type of radiation therapy, is well-tolerated. It has been shown to be safe and practical when combined with medications that travel through the bloodstream to treat colorectal cancer. Previous studies have not reported any major delays or issues with this treatment.

Surgical resection, which involves removing cancerous tissue, has become safer over the years, with fewer deaths occurring in the hospital. Studies confirm that both minimally invasive and open surgeries are safe options.

These findings suggest that using these treatments together with medications is generally safe for patients. However, individual experiences can differ, so discussing any concerns with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a combination of ablative therapy with standard chemotherapy, which could offer a new approach for treating colorectal cancer. Unlike traditional treatments that rely solely on chemotherapy, this trial incorporates techniques like SABR (Stereotactic Ablative Radiotherapy), surgical resection, and microwave ablation. These methods aim to precisely target and destroy cancer cells, potentially enhancing the effectiveness of the treatment. By combining these innovative therapies with standard chemotherapy, researchers hope to improve outcomes and offer more personalized treatment strategies for patients with colorectal cancer.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

In this trial, participants in Arm 1 will receive stereotactic ablative radiotherapy (SABR), with or without surgical resection and/or microwave ablation, alongside standard-of-care (SOC) chemotherapy. Previous studies have shown that microwave ablation effectively controls tumors that have spread to the liver from the colon without causing major complications. Research indicates that SABR can help patients with oligometastatic colorectal cancer live longer. Surgery to remove tumors has demonstrated excellent results in eliminating tumors and improving survival rates. These treatments aim to shrink or eliminate tumors effectively, potentially preventing their return. Participants in Arm 2 will receive SOC chemotherapy alone. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with colorectal cancer spread to up to 4 sites, excluding the brain and peritoneum. Must have had or be eligible for primary tumor resection, no more than 6 months of systemic therapy without disease progression, and meet specific health criteria like adequate blood counts and liver function.

Inclusion Criteria

My cancer did not worsen while on my last treatment.

My primary tumor has been removed or can be surgically removed.

My cancer does not have the BRAF V600E mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive total ablative therapy (TAT) consisting of SABR with or without surgical resection and/or microwave ablation, along with standard of care (SOC) chemotherapy. Imaging scans (CT, MRI, or PET/CT) are conducted throughout the trial.

Up to 5 years

Follow-up

Participants are monitored for safety, effectiveness, and recurrence after treatment. This includes assessments of overall survival, event-free survival, and time to local recurrence.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Microwave Ablation
• Resection
• Stereotactic Ablative Radiotherapy

Trial Overview The trial is comparing usual systemic therapy (like IV chemotherapy) alone versus adding total ablative therapy (intense radiotherapy called SABR, possibly combined with surgery or microwave ablation) to see if it better controls cancer that has spread in a limited way.

How Is the Trial Designed?

Group I: Arm 1 (TAT, SOC chemotherapy Experimental Treatment 7 Interventions

Patients undergo TAT on study, consisting of SABR with or without surgical resection and/or microwave ablation. Patients also receive SOC chemotherapy on study. Patients also undergo CT or MRI or PET/CT scans throughout the trial.

Group II: Arm 2 (SOC chemotherapy) Active Control 4 Interventions

Patients receive SOC chemotherapy on study. Patients also undergo Patients also undergo CT or MRI or PET/CT scans throughout the trial.

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?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The average annual cost of treating newly diagnosed colorectal cancer (CRC) patients was $97,400, with significant expenses attributed to chemotherapy, biologics, and various treatment settings, indicating a high financial burden on the healthcare system.

Healthcare costs for CRC treatment have increased by 73% from 2005 to 2009, primarily due to the adoption of new treatment regimens, the prevalence of metastasis, and the presence of comorbidities, highlighting the complexity and evolving nature of CRC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical costs associated with use of systemic therapy in adults with colorectal cancer. Seal, BS., Sullivan, SD., Ramsey, S., et al.[2023]

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 management of metastatic colorectal cancer (mCRC) requires a collaborative approach involving various specialists and is primarily based on chemotherapy combined with monoclonal antibodies targeting EGFR and VEGF.

Biomarkers such as RAS mutation and tumor sidedness are crucial for guiding EGFR-directed therapies, and additional molecular markers like BRAF mutations and MSI-status can expand treatment options for pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systemic Therapy of Metastatic Colorectal Cancer]. Modest, DP., von Bergwelt-Baildon, M.[2019]

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]

Recent advancements in chemotherapy and biologics have significantly improved treatment outcomes for colorectal cancer (CRC), particularly with the use of oxaliplatin in stage III colon cancer as the standard of care.

The introduction of KRAS mutational status as a predictive marker allows for more personalized treatment strategies in CRC, enhancing the potential for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy of colorectal cancer]. Reinacher-Schick, A., Pohl, M., Schmiegel, W.[2021]

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 a clinical trial involving 31 patients with liver metastasis from colorectal carcinoma, the combination of hepatic arterial chemoembolization and systemic 5-fluorouracil chemotherapy resulted in an overall response rate of 29%, with one complete response and eight partial responses observed.

Despite the treatment, the response rate and median time to disease progression (8 months) were similar to those achieved with standard systemic chemotherapy, leading researchers to conclude that this combined approach did not offer significant advantages and they do not plan to pursue it further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic chemoembolization combined with systemic infusion of 5-fluorouracil and bolus leucovorin for patients with metastatic colorectal carcinoma: A Southwest Oncology Group pilot trial. Leichman, CG., Jacobson, JR., Modiano, M., et al.[2013]

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]

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]

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]

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]

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 colorectal cancer treatment over the past 5 years have led to the introduction of new cytotoxic agents and targeted therapies that significantly prolong survival in patients with advanced disease.

The application of these novel therapies not only benefits advanced cases but has also been successfully used in the adjuvant setting, indicating a broader potential for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of colorectal carcinoma: standard chemotherapy and beyond. Eng, C., Abbruzzese, JL.[2018]

Recent advancements in cytotoxic and biologic agents have significantly improved survival rates for patients with metastatic colorectal cancer (mCRC).

Surgical intervention for liver and/or lung metastases has been shown to enhance long-term survival, highlighting the importance of integrating systemic chemotherapy with potentially curative surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for metastatic colorectal cancer: current questions. Zuckerman, DS., Clark, JW.[2018]

Citations

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Multi-institutional analysis of outcomes for thermosphere ... Thermosphere™-Microwave ablation is a safe and effective treatment for colorectal liver metastases with no registered biliary complications in ...

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Full article: Long-term outcomes following percutaneous ... Satisfactory overall survival and local tumor progression free survival can be achieved in patients with colorectal cancer liver metastases ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X18308359

A comparison of microwave thermosphere versus ... The results of the current study showed that for colorectal liver metastases treated with MTA versus RFA, local tumor control rate was better, despite shorter ...

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the SMAC study Thermosphere™-Microwave ablation is a safe and effective treatment for colorectal liver metastases with no registered biliary complications ...

5. ejcancer.com ejcancer.com/article/S0959-8049(23)00175-2/fulltext

A prospective multicentre trial on survival after Microwave ... Results from this prospective cohort trial show that treatment of small, resectable CRLM with SMWA results in similar patient OS as observed ...

6. hbsn.amegroups.org hbsn.amegroups.org/article/view/126362/html

long-term results of a retrospective cohort surgical experience Microwave ablation (MWA) outperformed radiofrequency ablation (RFA) in control of colorectal liver metastasis (CRLM), overall and when accounting for known ...

7. mdpi.com mdpi.com/2072-6694/13/6/1295

Comparing the Safety and Efficacy of Microwave Ablation ... Microwave ablation led to a high rate of curative ablation (94.7%) and a low rate of local recurrence (3.3%), with an overall survival rate of ...