BMX-001 + Radiation for Rectal Cancer

Overseen By Erin E Rogers, 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

Trial Summary

What is the purpose of this trial?

In this Phase 2 study, we will conduct an efficacy and safety study of the combination of investigational drug BMX-001, with short-course radiotherapy (SCRT) or long-course chemoradiotherapy (LCCRT) as part of total neoadjuvant therapy in newly diagnosed rectal adenocarcinoma (RAC) patients.

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.

What data supports the effectiveness of the treatment 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 therapies like chemotherapy and radiotherapy is a common approach to enhance treatment outcomes. ^{1 2 3 4 5}

How is the treatment BMX-001 + Radiation for rectal cancer different from other treatments?

The treatment BMX-001 combined with radiation for rectal cancer is unique because it integrates BMX-001, a novel component, with established radiation therapies like long-course chemoradiotherapy (LCCRT) and short-course radiotherapy (SCRT), potentially enhancing the effectiveness of preoperative treatment for rectal cancer. ^{1 2 4 5 6}

Research Team

Chi Lin, MD, PhD

Principal Investigator

University of Nebraska

Eligibility Criteria

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

Breast-feeding or pregnant

I have had rectal cancer before.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2019]

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

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States. [2022]

3. Switzerland 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. [2023]

4. England 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. [2023]

5. India pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Short-course radiotherapy for rectal cancer: real-world evidence in Argentina. [2023]