Adaptive Radiotherapy for Brain Tumor

Recruiting at 1 trial location

Overseen By Radiation Oncology Research Department

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Disqualifiers: Metastatic disease, Prior malignancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether extra MRI scans can enhance the effectiveness of radiation treatment for brain tumors, specifically targeting high-grade gliomas, an aggressive type of brain tumor. Participants will undergo standard radiation therapy (adaptive radiotherapy) and receive weekly brain MRIs to determine if adjustments improve outcomes. Suitable candidates include those diagnosed with certain brain tumors, such as glioblastoma, who are preparing to begin radiation treatment. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could improve future treatment strategies.

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.

What prior data suggests that this adaptive radiotherapy is safe for brain tumor treatment?

Research has shown that adaptive radiotherapy is generally well-tolerated. This treatment uses advanced imaging, such as MRI scans, to adjust radiation therapy more precisely for brain tumors. Although specific safety data on adaptive radiotherapy is not detailed, this method builds on standard radiotherapy techniques, which are widely used in cancer treatment.

The innovative use of MRI scans in adaptive radiotherapy aims to improve precision, potentially reducing side effects by targeting the tumor more accurately and protecting healthy tissue. The trial's "Not Applicable" phase label indicates that the treatment is not new or experimental like a drug might be. Instead, it focuses on refining technique rather than introducing a new, untested treatment.

Overall, adaptive radiotherapy is expected to have a safety profile similar to standard radiotherapy, which is generally accepted in medical practice. However, like any medical treatment, some risk of side effects exists, such as fatigue or skin irritation, but these are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about adaptive radiotherapy for brain tumors because it uses advanced imaging techniques, like weekly brain MRIs, to tailor treatment precisely to the tumor's size and shape as it changes during therapy. Unlike the standard radiotherapy that typically follows a fixed plan, this approach adapts to the patient's needs in real-time, potentially improving effectiveness and reducing damage to healthy brain tissue. This personalized method aims to enhance treatment outcomes and minimize side effects, making it a promising advancement in brain tumor care.

What evidence suggests that adaptive radiotherapy is effective for brain tumors?

Research has shown that adaptive radiotherapy, which participants in this trial will receive, might improve treatment for high-grade glioma, a type of brain tumor. This method uses MRI scans to adjust radiation doses more accurately. By adapting the treatment as the tumor changes, it could better target cancer cells and protect more healthy tissue. Early results suggest that adaptive radiotherapy can enhance the precision of radiation therapy. Although specific data on its effectiveness for high-grade glioma remains limited, this technique appears promising for improving outcomes by adjusting treatment in real-time. ^{2 3 4 6 7}

Who Is on the Research Team?

Tony J. Wang, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade gliomas like glioblastoma, who haven't had previous tumor treatments except biopsy or resection. They must have a Karnofsky performance status of 70+ and plan to receive standard radiotherapy. Pregnant women can't participate.

Inclusion Criteria

Females of childbearing potential must provide a negative pregnancy test prior to their first research MRI, as per institutional regulations.

I am scheduled for a specific radiotherapy plan, not a shortened course.

I had a physical exam within the last 28 days.

Exclusion Criteria

I have been cancer-free for at least 2 years, except for non-melanoma skin cancer.

Current or planned treatment with any other investigational agents for high grade glioma

I have only had a biopsy or surgery for my tumor, no other treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive radiotherapy per standard of care over 30-33 once-daily fractions with 7 brain MRIs each week, or 15 once-daily fractions with 4 brain MRIs each week for those receiving hypofractionated radiotherapy

6-7 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Adaptive Radiotherapy

Trial Overview The study tests if extra MRI scans during the weekly radiation treatment can improve outcomes for patients with aggressive brain tumors. It aims to adapt radiotherapy more precisely to the changes in the tumor's size and shape.

How Is the Trial Designed?

Group I: Adaptive Radiotherapy Experimental Treatment 1 Intervention

Subjects will receive radiotherapy per standard of care over 30-33 once-daily fractions in addition to 7 brain MRIs each in every week of treatment. Subjects receiving hypofractionated radiotherapy will receive radiotherapy per standard of care over 15 once-daily fractions in addition to 4 brain MRIs each in every week of treatment.

Adaptive Radiotherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer
• Metastatic urothelial cancer (approval being withdrawn)

Approved in European Union as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial cancer

Approved in Canada as Trodelvy for:

• Metastatic triple-negative breast cancer (mTNBC)
• Metastatic urothelial cancer

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

In a study of 50 patients with metastatic small cell lung cancer (mSCLC) who had been heavily pretreated, sacituzumab govitecan demonstrated a 14% objective response rate, with 60% of patients showing tumor shrinkage, indicating its potential efficacy as a treatment option.

The treatment was found to be generally safe, with manageable side effects; however, significant adverse events included neutropenia (34%) and fatigue (13%). This suggests that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Gray, JE., Heist, RS., Starodub, AN., et al.[2022]

Adaptive radiotherapy (ART) can significantly reduce the gross tumor volume (GTV) in patients with stage III non-small cell lung cancer (NSCLC), with an average reduction of 42.1%, particularly benefiting those undergoing concurrent chemoradiotherapy (cCRT).

The most effective time to implement ART is around the 15th treatment fraction, as this timing provides the best dosimetric advantages, especially for patients with larger tumors, while also allowing for better management of lung dose constraints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive radiotherapy for locally advanced non-small cell lung cancer, can we predict when and for whom? Berkovic, P., Paelinck, L., Lievens, Y., et al.[2018]

A total of 1,884 adverse event reports related to sacituzumab govitecan were analyzed, identifying 114 adverse event signals, with most occurring within 30 days of treatment initiation, highlighting the importance of monitoring for early reactions.

Risk factors for hospitalization due to adverse events included being male and experiencing conditions like colitis, febrile neutropenia, and sepsis, indicating specific patient profiles that may require closer observation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). Li, X., Zhang, L., Hu, S., et al.[2023]

Adaptive radiotherapy (ART) for glioblastoma significantly improved target coverage, with a median V95 of 98.3% for adaptive plans compared to 95.6% for fixed plans, indicating better delivery of radiation to the tumor.

ART also allows for a reduction in radiation exposure to normal brain tissue, particularly benefiting patients who have undergone gross total resection (GTR), while enhancing coverage for those with partial resection or biopsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective comparison of adaptive and fixed boost plans in radiotherapy for glioblastoma. Matsuyama, T., Fukugawa, Y., Kuroda, J., et al.[2022]

Adaptive radiotherapy (ART) for high-grade gliomas can enhance the precision of radiation targeting, leading to improved tumor control probability (TCP) while reducing the radiation dose to critical organs at risk (OARs).

The study suggests that implementing ART after 10 fractions of radiation therapy is optimal, as it results in better conformity to the planning target volume (PTV) and lower doses to sensitive areas like the pituitary and optic chiasm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study on the Appropriate Timing of Postoperative Adaptive Radiotherapy for High-Grade Glioma. Cao, Y., Tang, D., Xiang, Y., et al.[2022]

Stereotactic MR-guided adaptive radiotherapy (SMART) for pancreatic tumors showed no patients experiencing severe acute toxicities, with the most common side effects being mild (grade 1-2) symptoms like asthenia and nausea.

The study demonstrated promising outcomes with a median overall survival of 14.1 months and high local control rates (97% at 6 months), indicating that SMART is effective and safe for treating pancreatic tumors, with a notable secondary surgical resection rate in patients initially diagnosed with locally advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic MR-Guided Radiotherapy for Pancreatic Tumors: Dosimetric Benefit of Adaptation and First Clinical Results in a Prospective Registry Study. Michalet, M., Bordeau, K., Cantaloube, M., et al.[2022]

The introduction of tumor match and adaptive radiotherapy for non-small cell lung cancer patients led to a significant reduction in radiation pneumonitis, with symptomatic cases dropping from 50% to 20% and severe cases from 21% to 7%.

Patients receiving adaptive radiotherapy also experienced improved survival outcomes, with two-year progression-free survival increasing from 22% to 30% and overall survival rising from 43% to 56%, indicating enhanced treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefits for non-small cell lung cancer patients treated with adaptive radiotherapy. Møller, DS., Lutz, CM., Khalil, AA., et al.[2022]

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

Sacituzumab govitecan (SG) is an FDA-approved antibody-drug conjugate that has shown significant efficacy in treating metastatic triple-negative breast cancer, improving health-related quality of life and prolonging progression-free and overall survival in patients who have undergone multiple prior therapies.

Ongoing clinical trials are exploring the potential of SG for broader applications, including neoadjuvant and adjuvant therapies, combinations with immunotherapy, and treatment of various solid tumors, indicating its promise as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of sacituzumab govitecan in solid tumors. Veeraballi, S., Khawar, Z., Aslam, HM., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-anaplastic-astrocytoma-aa-10-2023-c4137

Adaptive Radiotherapy for Brain Tumor Sacituzumab govitecan has been studied in various cancers and generally shows a safe profile, but it can cause side effects like neutropenia (low white blood ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11306739/

Sacituzumab Govitecan in patients with breast cancer brain ... Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers.

3. askgileadmedical.com askgileadmedical.com/docs/trodelvy/trodelvy-use-with-radiation-therapy

For HCP's | Trodelvy® (sacituzumab govitecan-hziy) Use ... This document is in response to your request for information regarding the use of radiation therapy (RT) with Trodelvy® (sacituzumab govitecan-hziy [SG]).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01631552

Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults ... In Phase II, the primary objective is to evaluate the safety and efficacy of sacituzumab govitecan-hziy administered in 21-day treatment cycles at a dose ...

5. onclive.com onclive.com/view/sacituzumab-govitecan-upholds-efficacy-and-safety-in-real-world-mtnbc-population

Sacituzumab Govitecan Upholds Efficacy and Safety in ... Treatment with sacituzumab govitecan was effective and tolerable in real-world patients with mTNBC who received the agent in later-line settings.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11083716/

The Safety and Efficacy of the Combination of Sacituzumab ... We conducted a multi-center retrospective cohort study to assess the efficacy and safety of Sacituzumab govitecan and palliative radiotherapy.

7. nature.com nature.com/articles/s41467-024-50558-9

Sacituzumab Govitecan in patients with breast cancer ... Approximately 50% of all women with advanced TNBC will be diagnosed with brain metastases. The outcome of these patients is quite poor, with a ...