Ablative Therapy for Gastrointestinal Cancer

(LIVELONG Trial)

Overseen By Selina Laqui, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Davis

Must be taking: Systemic therapy

Disqualifiers: Intracranial lesions, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 3 months

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for individuals with certain gastrointestinal cancers, such as those affecting the stomach, bowel, or liver. The goal is to determine if adding focused treatments, like precise radiation or small burn techniques, can help when cancer starts to grow again but hasn't spread extensively. Researchers aim to discover if combining these treatments with ongoing cancer medication can delay the need to switch treatments. Individuals benefiting from their current cancer treatment but with up to five new or growing cancer spots might be suitable candidates. As an unphased trial, this study offers patients a unique opportunity to explore innovative treatment combinations that could enhance their current therapy.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications. You can continue your current systemic therapy, with a possible break of up to 30 days for the local ablative therapy.

What prior data suggests that locally ablative therapy is safe for treating gastrointestinal cancer?

Research has shown that stereotactic ablative radiotherapy (SABR) is generally safe and well-tolerated for treating certain types of cancer. In one study, patients with oligometastatic cancer experienced few serious side effects from SABR. Fatigue was the most common moderate side effect, affecting about 2% of patients. Only a few patients experienced serious effects, such as increased liver enzymes.

Another study found that SABR was a safe and effective treatment for individuals with pancreatic cancer that could not be surgically removed. This indicates that the treatment worked well without causing many problems for the patients.

Overall, these findings suggest that SABR is a promising treatment option with manageable side effects. However, discussing potential risks and benefits with a healthcare professional before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for gastrointestinal cancer, which often involve surgery, chemotherapy, or conventional radiation therapy, ablative local therapy uses highly focused techniques like Stereotactic Ablative Radiotherapy (SABR) or interventional radiology ablation. These methods precisely target cancerous tissues, minimizing damage to surrounding healthy tissue. Researchers are excited about these treatments because they offer a less invasive option with the potential for fewer side effects and quicker recovery times compared to standard treatments. Additionally, these therapies could be particularly beneficial for patients who aren't candidates for surgery, providing them with new hope for effective cancer management.

What evidence suggests that locally ablative therapy is effective for gastrointestinal cancer?

Research has shown that treatments targeting specific areas, such as stereotactic ablative radiotherapy (SABR), effectively treat some gastrointestinal cancers. For example, SABR has shown promising results in colorectal and pancreatic cancers. It can improve survival rates and is generally well-tolerated by patients. Some studies found that combining SABR with other treatments enhances its effectiveness against advanced cancers. These findings suggest that this type of therapy, which participants in this trial may receive, can be a powerful tool in managing cancer progression. ^{1 2 6 7 8}

Who Is on the Research Team?

Edward J. Kim

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

The LIVELONG trial is for adults over 18 with certain gastrointestinal cancers, like colorectal or stomach cancer, who have seen benefits from their current systemic therapy. They should have no more than five new or worsening metastatic lesions and be able to continue their present treatment after a short break for local therapy.

Inclusion Criteria

You have provided a signed and dated permission document.

I have liver cancer.

You agree to abide by the study protocols and remain involved until completion.

Exclusion Criteria

I have side effects from past treatments that prevent me from getting certain local therapies.

My brain tumor is getting worse.

I cannot undergo treatments that target specific areas due to my health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive systemic therapy with the addition of locally ablative therapies such as stereotactic ablative radiotherapy (SABR) or interventional radiology (IR) ablation therapy

3 months

Regular visits as per standard practices

Follow-up

Participants are monitored for disease control and adverse events, with a focus on safety and effectiveness after treatment

5 years

Periodic visits up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Locally ablative therapy

Trial Overview This phase 2 study tests if adding local ablative therapies (targeted treatments to destroy tumors) to ongoing systemic therapy can extend the time before treatment fails in patients with limited progression of gastrointestinal cancers.

How Is the Trial Designed?

Group I: Ablative local therapy Experimental Treatment 1 Intervention

Stereotactic ablative radiotherapy (SABR) or interventional radiology (IR) ablation therapy

Locally ablative therapy is already approved in European Union, United States for the following indications:

Approved in European Union as SAbR/SBRT for:

• Oligometastatic pulmonary disease from gastrointestinal malignancies
• Solid tumors

Approved in United States as SAbR/SBRT for:

• Oligometastatic pulmonary disease from gastrointestinal malignancies
• Solid tumors

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Stereotactic ablative radiotherapy (SABR) is a highly effective and low-toxicity treatment for metastatic tumors, achieving local control rates of about 80%.

SABR shows promise in treating oligometastatic patients, with pilot studies suggesting it may be 'curative' in 20-25% of cases, especially when combined with systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. Ricardi, U., Filippi, AR., Franco, P.[2013]

Stereotactic Ablative Radiotherapy (SABR) demonstrated a high local control rate of 90% at one year for treating oligometastatic colorectal cancer patients, with better outcomes for lesions treated with higher doses (≥ 60 Gy).

The treatment was found to be safe, with no cases of radiation-induced liver disease or severe toxicity, making SABR a viable option for patients with inoperable liver or lung metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach. Comito, T., Cozzi, L., Clerici, E., et al.[2022]

The introduction of stereotactic ablative body radiotherapy (SABR) for stage I non-small-cell lung cancer (NSCLC) at a Scottish cancer center has led to improved median survival rates, increasing from 32.5 months before SABR was available to 48.8 months after its establishment.

SABR has not only improved survival outcomes but also increased the proportion of patients receiving radical therapy, particularly among younger and healthier patients, indicating its effectiveness as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre. Stares, M., Lewis, G., Vallet, M., et al.[2023]

In a study of 163 colorectal cancer patients treated with stereotactic ablative radiotherapy (SBRT), the one-year local control rate was 83.8%, indicating that SBRT is an effective treatment option for oligometastatic disease.

Patients with nodal metastases had significantly better progression-free survival (9 vs 19 months) and overall survival (32 months vs not reached) compared to those with visceral metastases, highlighting the importance of the metastasis site in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior outcomes of nodal metastases compared to visceral sites in oligometastatic colorectal cancer treated with stereotactic ablative radiotherapy. O'Cathail, SM., Smith, T., Owens, R., et al.[2022]

In a study of 74 patients with locally advanced pancreatic cancer (LAPC) treated with chemotherapy followed by stereotactic ablative radiation therapy (SABR), the median overall survival was 19.6 months from diagnosis and 12.1 months from the start of SABR, indicating promising efficacy of this treatment approach.

SABR was found to be well-tolerated, with only a 2.7% rate of severe fatigue and late gastrointestinal toxicity, and better outcomes were associated with patients who had a Karnofsky Performance Status (KPS) score of ≥90, were younger than 70 years, and had no pain prior to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing patient selection for stereotactic ablative radiotherapy in patients with locally advanced pancreatic cancer after initial chemotherapy - a single center prospective cohort. Doppenberg, D., Lagerwaard, FJ., van Dieren, S., et al.[2023]

Stereotactic body radiotherapy (SBRT) is effective for treating early-stage non-small cell lung cancer (NSCLC) in patients who cannot undergo surgery, showing good outcomes and low toxicity for tumors located in the periphery.

However, the risk of severe toxicity increases for tumors near critical structures like the bronchial tree or mediastinum, highlighting the importance of careful dose-fractionation planning in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An optimal dose-fractionation for stereotactic body radiotherapy in peripherally, centrally and ultracentrally located early-stage non-small lung cancer. Zarębska, I., Harat, M.[2023]

Stereotactic Ablative Radiation Therapy (SABR) shows promising local control rates for patients with liver metastases from colorectal carcinoma, with 1, 2, and 3-year local control rates of 92.7%, 80.0%, and 61.2%, respectively, based on a study of 48 patients over a median follow-up of 26.6 months.

The study identified that larger tumor volumes negatively impact local control and overall survival, indicating that achieving higher biological effective doses is crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiation Therapy for Colorectal Liver Metastases. McDermott, RL., Dunne, EM., Zhao, Y., et al.[2023]

Stereotactic body radiotherapy (SBRT) demonstrated high local control rates in patients with oligometastatic pancreatic cancer, with 1-year and 2-year local control rates of 88.9% and 73.9%, respectively.

Patients treated with SBRT showed promising overall survival rates, with a median overall survival of 23 months and 1-year survival rate of 79.9%, suggesting that SBRT may be an effective local treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there an oligometastatic state in pancreatic cancer? Practical clinical considerations raise the question. Scorsetti, M., Comito, T., Franceschini, D., et al.[2022]

In a study of 383 patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR), higher doses of radiation (biologically effective dose) were associated with better local control, which significantly impacted survival rates for operable patients.

While overall survival was better in the Osaka group compared to Groningen, when adjusted for tumor size and patient performance status, there was no significant difference in survival between the two institutions, highlighting the importance of adequate dosing for effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-volume-response analysis in stereotactic radiotherapy for early lung cancer. Suzuki, O., Mitsuyoshi, T., Miyazaki, M., et al.[2018]

In a study of 47 patients with oligometastatic colorectal cancer treated with stereotactic body radiotherapy (SBRT), the 1-year local control rate was only 54%, indicating a need for improved treatment strategies.

Local recurrences were more common in metastases located in moving organs like the liver and lung, which had a significantly lower control rate (53%) compared to lymph nodes (79%), highlighting the importance of tailored treatment approaches that include respiratory motion management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of inadequate respiratory motion management in SBRT for oligometastatic colorectal cancer. Van den Begin, R., Engels, B., Gevaert, T., et al.[2022]

In a study of 202 patients with abdominopelvic cancers treated with stereotactic ablative radiotherapy (SABR), the volume of intestine receiving 25 Gy (V(25)) was identified as a strong predictor of severe intestinal toxicity, with a significant reduction in toxicity when V(25) was ≤ 20 ml.

The timing of SABR treatments also influenced toxicity, as patients receiving treatment over 4-8 days experienced significantly lower rates of severe intestinal toxicity compared to those treated on three consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe intestinal toxicity after stereotactic ablative radiotherapy for abdominopelvic malignancies. Bae, SH., Kim, MS., Kim, SY., et al.[2022]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

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