BMX-001 + Radiation for Rectal Cancer

Recruiting at 2 trial locations

Overseen By Samuel P Anderson, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Chi Lin, MD, PhD

Must not be taking: Corticosteroids, Coumarin anticoagulants

Disqualifiers: Pregnancy, Infection, Hypertension, others

Stay on Your Current Meds You can continue your current medications while participating

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: 3

118 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BMX-001, combined with radiation therapy for rectal cancer. Researchers aim to determine the effectiveness and safety of this combination for individuals with newly diagnosed rectal cancer that hasn't spread extensively. Participants will receive either short-course radiotherapy (SCRT) or long-course chemoradiotherapy (LCCRT), with or without the new drug. Those diagnosed with locally advanced rectal cancer and planning to undergo radiation therapy may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in rectal cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on corticosteroids, you must be on a stable or decreasing dose. If you are taking oral coumarin-derivative anticoagulants, you can continue but will need frequent monitoring to adjust the dose.

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

Research shows that BMX-001, when combined with short-course radiotherapy (SCRT), is generally safe. In earlier studies, BMX-001 reduced serious side effects to 14%, lower than the typical 21% to 36% seen with similar treatments. Short-course radiotherapy itself is known for its safety, with low rates of side effects, mostly mild stomach issues like inflammation of the small intestine.

For the combination of BMX-001 with long-course chemoradiotherapy (LCCRT), early results from other trials also indicate fewer serious side effects. Extensive studies in animals such as rats, mice, and dogs support BMX-001's use in humans. These findings suggest that BMX-001 is generally well-tolerated in people, but ongoing studies continue to assess its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BMX-001 in combination with radiation therapy for rectal cancer because it introduces a novel antioxidant approach. Unlike standard treatments that focus primarily on killing cancer cells, BMX-001 works by protecting healthy cells from the damaging effects of radiation, potentially reducing side effects. Additionally, BMX-001 is being tested with both short-course and long-course chemoradiotherapy, offering flexibility and possibly improved patient outcomes. This dual approach may lead to faster recovery and better quality of life for patients.

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

Studies have shown that BMX-001, when combined with radiation, can help reduce severe side effects in cancer treatment. Early research from other cancer trials indicates that BMX-001 decreases severe side effects from 21%-36% to 14%. In this trial, participants will receive either short-course radiotherapy (SCRT) or long-course chemoradiotherapy (LCCRT), with or without BMX-001. SCRT is already known to be effective for rectal cancer, providing good results with few side effects. Conversely, LCCRT has been shown to lower the chances of cancer recurrence and improve survival rates. BMX-001, when used with these treatments, aims to enhance these benefits by potentially improving tumor response and reducing side effects. ^{1 3 4 5 6}

Who Is on the Research Team?

Chi Lin, MD, PhD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

Adults over 18 (19 in Nebraska) with locally advanced rectal cancer who are fit for total neoadjuvant therapy can join. They must have certain blood counts, organ function tests, and imaging done recently. Pregnant or breastfeeding individuals, those with significant heart disease, uncontrolled hypertension, recent serious cardiovascular events, or a history of other cancers needing active treatment are excluded.

Inclusion Criteria

Serum SGOT and bilirubin ≤ 1.5 times upper limit of normal

I have advanced rectal cancer and will undergo intensive treatment before surgery to try to cure it.

I agree to use two effective birth control methods during and up to 12 months after the study.

Exclusion Criteria

I have had rectal cancer before.

Breast-feeding or pregnant

I have not needed IV antibiotics for an infection in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Safety Lead-in

Safety lead-in for patients receiving capecitabine prior to beginning the randomized trial for the Long Course Chemo-radiation (LCCRT) cohort

3 weeks

Multiple visits (in-person)

Randomized Treatment

Randomized trial involving Short Course Radiation Therapy (SCRT) or Long Course Chemo-radiation Therapy (LCCRT) with or without BMX-001

6-8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• BMX-001
• Long-course chemoradiotherapy (LCCRT)
• Short-course radiotherapy (SCRT)

Trial Overview The trial is testing the safety and effectiveness of BMX-001 when used with either short-course radiotherapy or long-course chemoradiotherapy in patients with newly diagnosed rectal adenocarcinoma as part of their pre-surgery treatment plan.

How Is the Trial Designed?

Group I: Arm C Experimental Treatment 1 Intervention

Long Course Chemo-Radiation Therapy (LCCRT) + BMX-001

Group II: Arm A Experimental Treatment 1 Intervention

Short Chemo-Radiation Therapy (SCRT) + BMX-001

Group III: Arm D Active Control 1 Intervention

Long Course Chemo-Radiation Therapy (LCCRT)

Group IV: Arm B Active Control 1 Intervention

Short Chemo-Radiation Therapy (SCRT)

Who Is Running the Clinical Trial?

Chi Lin, MD, PhD

Lead Sponsor

Trials

3

Recruited

190+

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

BioMimetix JV, LLC

Industry Sponsor

Trials

11

Recruited

700+

Published Research Related to This Trial

In a study of 44 patients with locally advanced rectal cancer (LARC) and metastatic disease treated with short-course radiotherapy (SCRT), 18.2% achieved a clinical complete response (cCR), allowing some to avoid surgery and adopt a watch-and-wait approach.

SCRT demonstrated low toxicity rates, but patients who received consolidation chemotherapy after SCRT experienced more adverse events compared to those who had induction chemotherapy first, highlighting the need for careful treatment planning by a multidisciplinary team.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course radiotherapy for rectal cancer: real-world evidence in Argentina. Tissera, NS., Freile, B., Waisberg, F., et al.[2023]

This study will evaluate the effectiveness of a combination treatment involving capecitabine, oxaliplatin, tislelizumab, and short-course hypofractionated radiotherapy in 50 patients with locally advanced rectal cancer, aiming for a primary endpoint of pathological complete response after treatment.

The trial will also assess important secondary outcomes such as 3-year disease-free survival and overall survival, which will help determine the long-term efficacy and safety of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining chemotherapy and tislelizumab with preoperative split-course hypofraction radiotherapy for locally advanced rectal cancer: study protocol of a prospective, single-arm, phase II trial. Zheng, R., Wang, BS., Li, Z., et al.[2023]

A meta-analysis of 11 studies involving 1984 patients found that preoperative short-course radiotherapy (SCRT) is as effective as long-course radiochemotherapy (LCRT) for long-term survival in locally advanced rectal cancer, with no significant differences in overall survival, disease-free survival, or local recurrence rates.

SCRT may be a preferable option in situations with long waiting lists or limited medical resources, as it provides similar efficacy to LCRT while potentially reducing treatment time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data. Wang, X., Zheng, B., Lu, X., et al.[2019]

A survey of 182 US radiation oncologists revealed that 96% prefer long-course chemoradiotherapy (LC-CRT) over short-course radiotherapy (SC-RT) for treating locally advanced rectal cancer, with many citing concerns about SC-RT's effectiveness in downstaging tumors for surgical options.

Despite evidence from randomized controlled trials showing no significant outcome differences between SC-RT and LC-CRT, SC-RT is rarely used, primarily due to concerns about insufficient tumor downstaging and the desire for longer follow-up, indicating a need for further research to assess the potential benefits of SC-RT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States. Mowery, YM., Salama, JK., Zafar, SY., et al.[2022]

The study analyzed the 100 most-cited articles on preoperative radiotherapy for rectal cancer, revealing that randomized and funded studies received significantly more citations, indicating a trend towards valuing rigorous research designs in this field.

There was no significant difference in citation rates between studies focusing on short-course radiotherapy (SC-RT) and long-course radio-chemotherapy (LC-RCHT), suggesting that both treatment approaches are equally recognized in the academic community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative radiotherapy for rectal cancer: A bibliometric analysis of the 100 most-cited research articles. Turkkan, G., Alkan, A.[2022]

Neoadjuvant short course radiotherapy (SCRT) followed by consolidation chemotherapy (CCT) resulted in a higher pathologic complete response (pCR) rate compared to conventional chemoradiotherapy (CRT), indicating better tumor response in locally advanced rectal cancer (LARC) patients, based on a review of 7507 patients from 14 cohorts.

SCRT + CCT also led to more sphincter-preservation surgeries without increasing toxicity or negatively impacting overall survival (OS) and disease-free survival (DFS), suggesting it is a safe and effective alternative treatment for LARC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy before Surgery for Treating Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis. Liao, CK., Kuo, YT., Lin, YC., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-2-rectal-carcinoma-5-2022-a2043

BMX-001 + Radiation for Rectal Cancer Research shows that preoperative short-course radiotherapy (SCRT) followed by chemotherapy can improve tumor response in rectal cancer, and combining different ...

2. trial.medpath.com trial.medpath.com/news/0be8902e00c7e714/drug-being-tested-to-address-side-effects-of-cancer-treatment-nebraska-medicine

BMX-001 Shows Promise in Reducing Side Effects of Cancer ... Early data from the anal cancer trial indicates a reduction in severe (Grade 3 or above) toxicity to 14%, compared to 21%–36% in historical data. The rectal ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40369294/

long-term results of a randomized controlled trial Short-course versus long-course neoadjuvant chemoradiotherapy in patients with rectal cancer: long-term results of a randomized controlled trial.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4587524/

Neoadjuvant Long-Course Chemoradiotherapy for Rectal ... The Swedish Rectal Cancer Trial showed statistically significant reduction in the local recurrence rates and increase in the overall survival rates at a median ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/68/NCT02990468/Prot_SAP_000.pdf

BMX-HN-001 A Phase 1/2 Trial of Concurrent Radiation ... Because there is a 50-85% five year survival rate for patients treated for head and neck cancers, due in part to a rapidly increasing segment of ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05254327/trial-of-the-efficacy-and-safety-of-short-and-long-course-radiation-therapy-with-without-bmx-001

Trial of the Efficacy and Safety of Short and Long Course ... In this Phase 2 study, we will conduct an efficacy and safety study of the combination of investigational drug BMX-001, with short-course ...