Ablative Therapy for Gastrointestinal Cancer

(LIVELONG Trial)

Overseen by Edward J. Kim

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of California, Davis

Must be taking: Systemic therapy

Disqualifiers: Intracranial lesions, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a phase 2 pragmatic study that evaluates the clinical benefit of continuing systemic therapy with the addition of locally ablative therapies for oligo-progressive solid tumors as the primary objective. The primary outcome measure is the time to treatment failure (defined as time to change in systemic failure or permanent discontinuation of therapy) following locally ablative 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 data supports the effectiveness of the treatment for gastrointestinal cancer?

Research shows that stereotactic ablative radiotherapy (SABR) has been effective in treating certain types of cancer, such as colorectal and pancreatic cancer, by targeting and controlling tumors in specific areas. This suggests that similar approaches might be beneficial for gastrointestinal cancers as well. ^{1 2 3 4 5}

Is ablative therapy for gastrointestinal cancer generally safe for humans?

Ablative therapy, like Stereotactic Ablative Radiotherapy (SABR), has been used for various cancers and can be safe, but there are risks of serious complications, especially when tumors are near sensitive areas like the intestines or bronchial tree. Strategies to reduce these risks are important to ensure safety. ^{3 6 7 8 9}

How is the treatment Locally Ablative Therapy (SAbR/SBRT/LAT) different from other treatments for gastrointestinal cancer?

Locally Ablative Therapy, also known as Stereotactic Ablative Radiotherapy (SAbR) or Stereotactic Body Radiotherapy (SBRT), is unique because it delivers very precise, high doses of radiation directly to tumors while minimizing damage to nearby healthy organs. This approach is particularly beneficial for patients with limited metastatic disease, as it can achieve high local control rates and potentially improve prognosis in some cases. ^{2 3 10 11 12}

Research Team

Edward J. Kim

Principal Investigator

University of California, Davis

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Locally ablative therapy (Procedure)

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.

Participant Groups

Group I: Ablative local therapy Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Rakesh Dixit

University of California, Davis

Chief Executive Officer since 2024

PhD in Biochemistry and Molecular Biology from the University of California, Davis

Suresh Mahabhashyam

University of California, Davis

Chief Medical Officer since 2020

MD from Bangalore Medical College

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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 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]

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]

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 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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Is there an oligometastatic state in pancreatic cancer? Practical clinical considerations raise the question. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Superior outcomes of nodal metastases compared to visceral sites in oligometastatic colorectal cancer treated with stereotactic ablative radiotherapy. [2022]

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

Stereotactic Ablative Radiation Therapy for Colorectal Liver Metastases. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

Dose-volume-response analysis in stereotactic radiotherapy for early lung cancer. [2018]

5. Switzerland 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. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Severe intestinal toxicity after stereotactic ablative radiotherapy for abdominopelvic malignancies. [2022]

7. Singapore 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. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Impact of SABR on Stage I Non-Small-Cell Lung Cancer Outcomes at a Scottish Cancer Centre. [2023]

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

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

10. England pubmed.ncbi.nlm.nih.gov

New concepts and insights into the role of radiation therapy in extracranial metastatic disease. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach. [2022]

12. Ireland pubmed.ncbi.nlm.nih.gov

Impact of inadequate respiratory motion management in SBRT for oligometastatic colorectal cancer. [2022]