NG-350A + Chemoradiotherapy for Rectal Cancer

(FORTRESS Trial)

Recruiting at 2 trial locations

Overseen By Vice President Head of Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Akamis Bio

Must not be taking: Immunosuppressants, Anti-CD40 antibody

Disqualifiers: Recurrent cancer, Metastatic disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The FORTRESS trial (NG-350A-03) is an open-label, single-arm, and multicentre trial of NG-350A in combination with chemoradiotherapy (CRT) in adult patients with locally advanced rectal cancer (LARC) and at least one risk factor for local or distant recurrence.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on systemic immunosuppressive therapy or have had other anti-cancer treatments in the past 12 months, you may not be eligible to participate.

What data supports the effectiveness of the treatment NG-350A + Chemoradiotherapy for Rectal Cancer?

Research shows that using capecitabine (a chemotherapy drug) with radiation can effectively shrink rectal tumors before surgery, similar to another drug called 5-FU. This combination is considered a good option for treating advanced rectal cancer. ^{1 2 3 4 5}

What safety data exists for NG-350A + Chemoradiotherapy for Rectal Cancer?

The research articles reviewed do not provide specific safety data for NG-350A combined with chemoradiotherapy for rectal cancer. However, chemoradiotherapy, a common treatment for various cancers, is known to have substantial side effects, including toxicity, as seen in treatments for anal and prostate cancers. ^{6 7 8 9 10}

How does the drug NG-350A differ from other treatments for rectal cancer?

NG-350A is unique because it is being tested in combination with chemoradiotherapy, which is a treatment that uses both chemotherapy and radiation therapy together. This approach is different from the standard treatments that typically involve surgery followed by chemotherapy and radiation separately. The combination aims to enhance the effectiveness of the treatment by potentially increasing the complete response rates before surgery. ^{1 3 11 12 13}

Eligibility Criteria

This trial is for adults with advanced rectal cancer who are not pregnant or breastfeeding, can perform daily activities (ECOG 0-1), agree to use contraception, and have stable vital organ functions. It's specifically for those with a certain type of genetic status in their cancer cells (MSS/pMMR) and who are chosen for neoadjuvant chemoradiotherapy.

Inclusion Criteria

I have signed a consent form to participate.

I am not pregnant or breastfeeding.

I agree to follow the study's birth control requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NG-350A in combination with chemoradiotherapy for locally advanced rectal cancer

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Capecitabine
• NG-350A
• Radiotherapy

Trial Overview The FORTRESS trial tests NG-350A given through IV along with standard chemoradiotherapy, which includes radiation therapy and oral Capecitabine. The goal is to see how well this combination works in treating locally advanced rectal cancer.

Participant Groups

Group I: NG-350A plus CRT during a 12-week active study treatment period Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Akamis Bio

Lead Sponsor

Trials

13

Recruited

820+

Findings from Research

Neoadjuvant chemoradiation, particularly with fluorouracil (5-FU) plus radiation, is now the preferred treatment for stage II/III rectal cancer, showing lower local relapse rates and better safety compared to postoperative treatments.

Capecitabine (Xeloda) plus radiation has been found to be as effective as 5-FU plus radiation, making it a viable alternative, while combinations with oxaliplatin or irinotecan show promise for improved outcomes and warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemoradiation for rectal cancer: is more better? Patel, A., Puthillath, A., Yang, G., et al.[2018]

In a study of 100 patients undergoing chemoradiotherapy for localized anal cancer, patient-reported outcomes (PROs) indicated a higher incidence of acute toxicity compared to physician-assessed toxicity (CTCAE), highlighting the importance of incorporating PROs in evaluating treatment effects.

Proton therapy demonstrated superior dosimetric planning compared to IMRT and VMAT, suggesting it may reduce radiation exposure to surrounding healthy tissues, potentially leading to lower toxicity in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization. Kronborg, C., Serup-Hansen, E., Lefevre, A., et al.[2019]

In a review of 21 randomized controlled trials involving 9040 patients with nonmetastatic prostate cancer, it was found that acute adverse events (AEs) were primarily reported by clinicians, while patient-reported outcomes (PROs) were underutilized, especially for late AEs.

The study highlights a gap in incorporating patient perspectives in reporting AEs related to radical radiation therapy, suggesting a need for standardized PRO assessments to better capture patient experiences and improve treatment evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and Late Adverse Events Associated With Radical Radiation Therapy Prostate Cancer Treatment: A Systematic Review of Clinician and Patient Toxicity Reporting in Randomized Controlled Trials. Holch, P., Henry, AM., Davidson, S., et al.[2022]

For clinically resectable rectal cancer, two main treatment approaches exist: surgery followed by postoperative therapy for certain tumor stages, or preoperative therapy followed by surgery and additional postoperative therapy for more advanced tumors.

New chemotherapeutic agents are being tested in combination with pelvic radiation, particularly in preoperative settings, showing promising early results with higher complete response rates compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality therapy of resectable rectal cancer: current approaches. Minsky, BD.[2005]

References

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

A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Comparison of two preoperative chemoradiotherapy regimens for locally advanced rectal cancer: capecitabine alone versus capecitabine plus irinotecan. [2021]

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

Neoadjuvant chemoradiation for rectal cancer: is more better? [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Current status of locally advanced rectal cancer therapy and future prospects. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

Oxaliplatin plus raltitrexed in the treatment of patients with advanced colorectal cancer: a phase II study. [2018]

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

Evaluation of Depression, Anxiety, and Sexual Function in Rectal Cancer Patients Before and After Neoadjuvant Chemoradiotherapy. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization. [2019]

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

Acute and Late Adverse Events Associated With Radical Radiation Therapy Prostate Cancer Treatment: A Systematic Review of Clinician and Patient Toxicity Reporting in Randomized Controlled Trials. [2022]

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

Development of a set of nomograms to predict acute lower gastrointestinal toxicity for prostate cancer 3D-CRT. [2019]

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

Grading-system-dependent volume effects for late radiation-induced rectal toxicity after curative radiotherapy for prostate cancer. [2008]

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

Combined-modality therapy of rectal cancer with oxaliplatin-based regimens. [2019]

12. Italy pubmed.ncbi.nlm.nih.gov

Combined modality therapy of resectable rectal cancer: current approaches. [2005]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Oxaliplatin-5-fluorouracil and ionizing radiation. Importance of the sequence and influence of p53 status. [2018]