Local and Systemic Therapy for Cancer

Overseen By Ethan Ludmir, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Metastatic effusion, Leptomeningeal disease, Peritoneal carcinomatosis, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on treatment response

300 Participants Needed

Trial Summary

What is the purpose of this trial?

To find out if local consolidation therapy (such as radiation therapy with or without other local therapies such as surgery, ablation \[the removal or destruction of a body part or tissue or its function\], or embolization \[a procedure that uses particles, such as tiny gelatin sponges or beads, to block a blood vessel\]) to all progressive sites of disease can help to control the disease compared with next-line systemic therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It's best to discuss your specific medications with the trial team to understand any potential requirements or adjustments.

What data supports the effectiveness of the treatment Local Consolidation Therapy, Next-line Systemic Therapy, Chemotherapy, Targeted Therapy, Immunotherapy, Hormone Therapy for cancer?

Research shows that combining different treatments, like chemotherapy and radiation, can improve survival rates in patients with advanced breast cancer. For example, patients with inflammatory breast cancer, once considered untreatable, now have a 5-year survival rate of 35-60% with combined therapies. Additionally, local consolidative therapy has been associated with improved survival in patients with certain types of lung cancer. ^{1 2 3 4 5}

What safety data exists for Local and Systemic Therapy for Cancer?

Research shows that cancer treatments like chemotherapy, immunotherapy, and targeted therapies can have significant side effects that affect quality of life. Studies have developed methods to identify severe toxicities from these treatments, and new therapies are approved each year with side effects that are not fully understood. It's important to monitor and manage these side effects to ensure patient safety. ^{6 7 8 9 10}

How is Local Consolidation Therapy different from other treatments for cancer?

Local Consolidation Therapy (LCT) is unique because it targets all sites of disease in patients with limited metastatic cancer, aiming to improve overall survival by optimizing disease control. Unlike standard systemic treatments that address widespread cancer, LCT focuses on treating specific tumor sites, which can be particularly beneficial for patients with oligometastatic non-small cell lung cancer. ^{3 11 12 13 14}

Research Team

Ethan Ludmir

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for individuals with cancer that has spread (metastatic) but only to a limited number of sites and is progressing despite treatment. Participants should be responding well to current systemic therapy except in a few areas.

Inclusion Criteria

My recent scans show limited cancer progression.

My organ functions are within the required range.

I am a candidate for radiation therapy for my disease.

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.

I have fluid buildup due to cancer spread.

My cancer has spread to the lining of my abdomen.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive local consolidation therapy (LCT) or next-line systemic therapy (NLST) based on their assigned group

Varies based on treatment response

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Extension

Participants may cross over to receive LCT if progression occurs in the NLST arm

Treatment Details

Interventions

• Local Consolidation Therapy
• Next-line Systemic Therapy

Trial Overview The study aims to compare the effectiveness of local consolidation therapy, like radiation or surgery, on all progressing cancer sites versus starting a new systemic treatment regimen.

Participant Groups

Group I: NLST Arm Experimental Treatment 1 Intervention

Participants are assigned to Group 1, participants will be treated with next-line systemic therapy. The specific next-line systemic therapy will be determined by your doctor. - If progression occurs (the disease gets worse), participants may cross over to Group 2 and receive LCT.

Group II: LCT Arm Experimental Treatment 1 Intervention

Participants are assigned to Group 2, participants will be treated with LCT and then continue on same systemic therapy participants have been receiving followed by the next line systemic of therapy (if applicable). The specific treatments will be determined by your doctor.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Combined modality therapy, which includes primary chemotherapy followed by surgery or radiation, is the preferred treatment for locally advanced breast cancer, leading to significant tumor size reduction in over 50% of cases and down-staging in about 70% of patients.

This approach has dramatically improved outcomes for patients with inflammatory breast cancer, transforming it from a fatal condition to one with 5-year survival rates of 35-60%, and potentially one-third of patients surviving beyond 10 years without recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidisciplinary management of advanced primary and metastatic breast cancer. Hortobagyi, GN.[2022]

Patients with operable locally advanced breast cancer show improved survival rates when treated with a combination of surgery or radiation followed by systemic chemotherapy, compared to those receiving only local treatments.

Induction chemotherapy has led to high response rates, particularly in patients with inflammatory breast cancer, with 30% to 50% achieving disease-free status 5 years post-diagnosis, highlighting the effectiveness of combined modality therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive management of locally advanced breast cancer. Hortobagyi, GN.[2022]

In a study of 194 patients with synchronous oligometastatic non-small-cell lung cancer (NSCLC), comprehensive local consolidative therapy (LCT) was linked to improved overall survival, with a hazard ratio of 0.67, indicating a significant benefit for patients receiving treatment to all sites of disease.

The greatest survival benefits from comprehensive LCT were observed in patients without thoracic nodal disease or bone metastases, suggesting that the effectiveness of LCT may vary based on the extent and location of metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Overall Survival With Comprehensive Local Consolidative Therapy in Synchronous Oligometastatic Non-Small-Cell Lung Cancer. Mitchell, KG., Farooqi, A., Ludmir, EB., et al.[2021]

In a study of 12 patients with oligometastatic breast cancer, consolidative radiation therapy combined with high-dose chemotherapy resulted in a 10-year progression-free survival (PFS) rate of 33% and an overall survival (OS) rate of 55%, indicating potential long-term benefits from aggressive local treatment.

The study demonstrated a high rate of durable local control (87.5%) of treated lesions, suggesting that targeted radiation therapy can effectively manage oligometastatic sites, even as modern systemic therapies evolve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligometastatic Breast Cancer Patients Treated with High-Dose Chemotherapy and Targeted Radiation: Long-Term Follow-Up of a Phase II Trial. Ladbury, C., Hao, C., Ruel, C., et al.[2022]

In a study of 128 patients with locally advanced breast carcinoma, a combined treatment approach using preoperative and postoperative FEC chemotherapy, surgery, and radiotherapy resulted in a 60% clinical response rate, with 5% achieving complete responses and 55% partial responses.

The median overall survival was 54 months, with a 5-year overall survival rate of 49%, indicating that this multimodal strategy can improve outcomes compared to single treatment modalities in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodality treatment of 128 patients with locally advanced breast carcinoma in the era of mammography screening using standard polychemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide: prognostic and therapeutic implications. Karlsson, YA., Malmström, PO., Hatschek, T., et al.[2013]

In a meta-analysis of 13 real-world studies involving 1885 patients with stage III non-small cell lung cancer, consolidation therapy with durvalumab after chemoradiation showed a 12-month overall survival rate of 90% and a progression-free survival rate of 62%, indicating its efficacy aligns with results from the PACIFIC trial.

The study found that while the incidence of all-grade pneumonitis was 35%, it was higher in older patients and those from Asian regions, suggesting that age and geographic factors may influence the safety profile of durvalumab in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Safety and Efficacy of Consolidation Durvalumab After Chemoradiation Therapy for Stage III Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis. Wang, Y., Zhang, T., Huang, Y., et al.[2022]

A toolkit called the Chemotherapy Audit Toolkit (CAT) was developed to improve the safety and effectiveness of systemic anti-cancer therapy (SACT) prescribing in Victorian public health services, following incidents of off-protocol prescribing.

Post-implementation surveys revealed that while 20% of health services were actively using the toolkit and 35% were in the process of implementing it, 45% had not utilized it, indicating a need for increased adoption and support, especially in light of challenges posed by the COVID-19 pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VicTAG chemotherapy audit toolkit: Improving chemotherapy quality and safety. O'Connor, S., Matthews, H., Hornby, C.[2023]

In a study of 203 patients with locally advanced non-small-cell lung cancer, those who received consolidation chemotherapy (CCT) after concurrent chemoradiotherapy had a significantly better overall survival (27 months vs. 16 months) and a 5-year survival rate of 30.4% compared to 22.5% for those who did not receive CCT.

CCT did not increase treatment-related toxicities compared to those who only received chemoradiotherapy, suggesting it is a safe option that can enhance survival, particularly for specific patient groups such as younger males and those with non-squamous histology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy--retrospective analysis of 203 cases. Liu, L., Bi, N., Ji, Z., et al.[2018]

A new coding framework was developed and validated to identify severe acute toxicities in colon cancer patients treated with systemic anti-cancer therapy (SACT), showing a 26.4% toxicity rate in adjuvant therapy and 53.4% in metastatic cases.

The framework revealed that specific SACT regimens, such as those including bevacizumab, were associated with higher rates of severe toxicities like bleeding and gastrointestinal issues, highlighting the importance of monitoring these effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of a coding framework to identify severe acute toxicity from systemic anti-cancer therapy using hospital administrative data. Boyle, JM., Cowling, TE., Kuryba, A., et al.[2022]

Modern multimodal tumor therapies, which include radiotherapy, chemotherapy, immunotherapy, and targeted therapies, can lead to significant acute and long-lasting side effects that negatively impact patients' quality of life and survival.

The paper highlights the need for better characterization of side effects from newly approved therapies and provides recommendations for monitoring and managing these effects in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. Rassaf, T., Totzeck, M., Backs, J., et al.[2021]

In a study of 436 patients with oligometastatic non-small cell lung cancer, local consolidative treatment (LCT) significantly improved overall survival (OS) in most risk groups, highlighting its potential efficacy in this patient population.

However, smokers with advanced T3/4 disease did not show a survival benefit from LCT, suggesting that the effectiveness of this treatment may vary based on specific patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recursive partitioning analysis of patients with oligometastatic non-small cell lung cancer: a retrospective study. Zhang, JT., Liu, SY., Yan, HH., et al.[2020]

A review of 67 studies on consolidation systemic therapy (ST) after concurrent radiotherapy (RT) for locally advanced nonsmall cell lung cancer (NSCLC) revealed that only 54% evaluated patient responses after the initial treatment phase, and only 21% provided specific response data.

There is a significant gap in understanding how different treatment responses impact patient outcomes, as no studies reported survival rates or failure patterns based on responses achieved before the consolidation phase, which could hinder effective treatment decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation Systemic Therapy in Locally Advanced, Inoperable Nonsmall Cell Lung Cancer-How to Identify Patients Which Can Benefit from It? Jeremić, B., Mariamidze, E., Shoshiashvili, I., et al.[2023]

Radical local treatment (LT) for patients with oligometastatic disease has been shown to significantly improve overall survival (OS) compared to systemic treatment alone, with a median OS increase of about two years in those with synchronous metastases and stable primary tumors.

While local treatment can enhance survival, it also raises the risk of grade III side effects by approximately 10%, indicating that careful patient selection and interdisciplinary evaluation are essential for its implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Local Treatment in Oligometastatic and Oligoprogressive Cancer. Haussmann, J., Matuschek, C., Bölke, E., et al.[2020]

Ablative therapies are most effective for solid tumors smaller than 3 cm, achieving complete response, but their effectiveness decreases as tumor size increases.

Combining different treatment modalities may improve local control rates for larger tumors, but the overall prognosis for patients with advanced disease may not benefit if the cancer is progressing in other areas, highlighting the need for further randomized trials to assess the effectiveness of combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing ablation: synergies with regional and systemic therapies. Kadivar, F., Soulen, MC.[2013]

References

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

Multidisciplinary management of advanced primary and metastatic breast cancer. [2022]

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

Comprehensive management of locally advanced breast cancer. [2022]

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

Improved Overall Survival With Comprehensive Local Consolidative Therapy in Synchronous Oligometastatic Non-Small-Cell Lung Cancer. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Oligometastatic Breast Cancer Patients Treated with High-Dose Chemotherapy and Targeted Radiation: Long-Term Follow-Up of a Phase II Trial. [2022]

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

Multimodality treatment of 128 patients with locally advanced breast carcinoma in the era of mammography screening using standard polychemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide: prognostic and therapeutic implications. [2013]

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

Real-World Safety and Efficacy of Consolidation Durvalumab After Chemoradiation Therapy for Stage III Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

VicTAG chemotherapy audit toolkit: Improving chemotherapy quality and safety. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy--retrospective analysis of 203 cases. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Development and validation of a coding framework to identify severe acute toxicity from systemic anti-cancer therapy using hospital administrative data. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. [2021]

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

Recursive partitioning analysis of patients with oligometastatic non-small cell lung cancer: a retrospective study. [2020]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Consolidation Systemic Therapy in Locally Advanced, Inoperable Nonsmall Cell Lung Cancer-How to Identify Patients Which Can Benefit from It? [2023]

13. Germany pubmed.ncbi.nlm.nih.gov

The Role of Local Treatment in Oligometastatic and Oligoprogressive Cancer. [2020]

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

Enhancing ablation: synergies with regional and systemic therapies. [2013]