Immunotherapy + Chemoradiation for Rectal Cancer

Not currently recruiting at 4 trial locations

Overseen By Brendan Paulman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Immunosuppressants, Antineoplastics

Disqualifiers: Metastatic disease, Autoimmune disease, 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: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for rectal cancer to determine their effectiveness in eliminating cancer cells. Participants will receive either a mix of chemotherapy and radiation or the same combination with an additional experimental drug, APX005M, an immunotherapy. The researchers aim to see if this approach can improve the pathologic complete response rate, meaning the cancer cells are completely gone after treatment. Individuals with rectal adenocarcinoma who haven't had prior treatment and possess certain high-risk features may be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study drug. It's best to discuss your specific medications with the trial team.

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

Research has shown that APX005M, combined with mFOLFOX chemotherapy and radiation therapy, is under study to determine if it can enhance the effectiveness of rectal cancer treatments. Previous patients have generally tolerated this combination well, experiencing side effects similar to those from standard chemotherapy and radiation. Some patients may encounter mild to moderate side effects like tiredness or nausea, which are common with these treatments.

mFOLFOX is a standard chemotherapy for rectal cancer and is usually well-tolerated. Common side effects can include tiredness, nausea, and a temporary drop in blood cell counts, which can increase the risk of infection.

Overall, the treatments tested in this trial appear to have a safety profile similar to other treatments in their categories. Since this trial is in Phase 2, the treatments have already passed initial safety tests in earlier studies. However, ongoing research remains important to further confirm their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rectal cancer because they combine immunotherapy with chemoradiation in novel ways. The investigational treatment, APX005M, works alongside the mFOLFOX regimen, potentially boosting the body's immune response to cancer cells, which is different from traditional chemotherapy alone that primarily targets cancer cells directly. Additionally, this approach integrates immunotherapy with radiation therapy, which could enhance the effectiveness of both treatments. This combination could offer a more powerful attack on cancer cells, potentially improving outcomes for patients compared to standard treatments like surgery or chemotherapy alone.

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

Research has shown that APX005M, a drug that activates the immune system, may help the body fight cancer cells. In this trial, one group of participants will receive APX005M combined with mFOLFOX and radiation therapy. This combination makes cancer cells more sensitive to chemoradiation, which mixes chemotherapy and radiation therapy. Previous studies have found that combining immune-boosting treatments with traditional methods can lower the chances of cancer recurrence and improve survival rates. Specifically, patients who received similar treatments had a 27% lower chance of cancer returning compared to those who received standard treatments. This suggests that using APX005M with mFOLFOX and radiation could effectively treat rectal cancer. Meanwhile, another group in this trial will receive radiation therapy and mFOLFOX without APX005M as a comparator. ^{1 6 7 8 9}

Who Is on the Research Team?

Todd Aguilera, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

Adults diagnosed with locally advanced rectal adenocarcinoma who haven't had previous treatments for it. They must be in good physical condition (ECOG 0-1) and have certain high-risk features or stage II/III cancer. Participants need proper organ and marrow function, not be pregnant or nursing, agree to use contraception, and can't have HIV/AIDS, hepatitis B/C, other cancers within the last 3 years (with exceptions), serious illnesses that could affect study participation, known autoimmune diseases (with exceptions), recent live vaccines, lung disease history, or prior specific immunotherapies.

Inclusion Criteria

FOCBP must agree to use highly-effective method(s) of contraception (Appendix A) during the study and for 90 days after the last dose of study drugs.

I am fully active or can carry out light work.

I have been diagnosed with rectal cancer.

Exclusion Criteria

I haven't had cancer treatment in the last 3 years, except for easily treatable types.

I have not received a live vaccine in the last 6 weeks.

I have had radiation therapy to my pelvic area before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive short-course radiotherapy consisting of 5Gy x 5 to the pelvis

1 week

5 visits (in-person)

Chemotherapy

Participants receive mFOLFOX chemotherapy with or without APX005M for six cycles

12 weeks

6 visits (in-person)

Surgery

Participants undergo trans abdominal resection (TME) after chemotherapy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• APX005M
• mFOLFOX
• Radiation Therapy

Trial Overview The trial is testing if adding APX005M to standard chemotherapy (mFOLFOX) plus radiation therapy improves complete response rates in rectal cancer patients compared to just mFOLFOX with radiation. The goal is to see which treatment better eliminates all signs of cancer before surgery.

How Is the Trial Designed?

Group I: APX005M on day 3 of RT & day 3 of cycles 1-5 of mFOLFOX Experimental Treatment 1 Intervention

On Day 3 of Cycles 1-5 of each mFOLFOX treatment, participants will receive another dose of APX005M. The sequence of administration of APX005M in combination with mFOLFOX. In Cycle 6, participants will receive only mFOLFOX. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study.

Group II: Radiation Therapy 5Gy x 5 days, mFOLFOX Active Control 1 Intervention

Participants randomized to Arm 2 will receive short-course RT and mFOLFOX regimen, except that participants will not receive any of the study drug. After completing the last planned dose of mFOLFOX, participants will be considered off-protocol directed therapy and undergo planned TME, per institutional standards, and proceed to the follow-up portion of this study.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Apexigen America, Inc.

Industry Sponsor

Trials

12

Recruited

630+

Apexigen, Inc.

Industry Sponsor

Trials

12

Recruited

630+

Published Research Related to This Trial

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 nonrandomized phase II trial involving 259 patients with stage II or III rectal cancer, adding modified FOLFOX6 chemotherapy after chemoradiotherapy improved disease-free survival rates, indicating a potential benefit in treatment outcomes.

The study found that the number of chemotherapy cycles received was linked to better survival outcomes, suggesting that neoadjuvant consolidation chemotherapy not only enhances the likelihood of a complete pathological response but also improves overall treatment compliance and long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial. Marco, MR., Zhou, L., Patil, S., et al.[2019]

In a phase 2 trial involving 80 patients with rectal adenocarcinoma, short-course radiation therapy followed by mFOLFOX6 chemotherapy resulted in stable quality of life (QOL) outcomes one year after treatment, indicating that the regimen is well-tolerated by patients.

Patients with an ostomy reported significantly lower functional well-being and colorectal cancer-specific quality of life compared to those without an ostomy, highlighting the impact of surgical outcomes on patient experiences post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life Outcomes From a Phase 2 Trial of Short-Course Radiation Therapy Followed by FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer. Khwaja, SS., Roy, A., Markovina, S., et al.[2022]

Intensity-modulated radiotherapy (IMRT) for prostate cancer patients showed a greater tumor control probability (TCP) compared to conventional three-dimensional conformal radiotherapy (3DCRT), with IMRT allowing for a higher mean dose to the prostate while using fewer treatment fractions (35 vs. 37).

Normal tissue complication probability (NTCP) was generally lower for IMRT than for 3DCRT, indicating that IMRT can reduce the risk of complications in sensitive organs while effectively targeting the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate. Luxton, G., Hancock, SL., Boyer, AL.[2022]

Moderately hypofractionated radiotherapy (RT) for localized prostate cancer shows a slight increase in acute gastrointestinal (GI) adverse events compared to conventional RT, with a 9.8% higher risk of GI events greater than grade 2.

The analysis of 13 studies indicates that moderately hypofractionated RT is generally equivalent to conventional RT in terms of genitourinary (GU) adverse events, suggesting it is a safe alternative for treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity after moderately hypofractionated versus conventionally fractionated prostate radiotherapy: A systematic review and meta-analysis of the current literature. Francolini, G., Detti, B., Becherini, C., et al.[2021]

In a study of 421 patients undergoing salvage radiotherapy (SRT) after prostate surgery, the use of advanced techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) significantly reduced the incidence of late gastrointestinal (GI) toxicities to 4.8%.

However, increasing the radiation dose to 68 Gy or more was linked to a higher risk of genitourinary (GU) toxicities, indicating that while advanced techniques can help minimize some side effects, higher doses may still pose risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. Tomita, N., Uchiyama, K., Mizuno, T., et al.[2021]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

In a study of 32 patients with locally advanced rectal cancer and liver-only metastases, the combination of mFOLFOX6 chemotherapy followed by short-course radiotherapy (SCRT) was effective, achieving a complete surgical resection (R0) in 63% of patients.

The treatment regimen was safe, with only one patient discontinuing due to toxicity and no treatment-related deaths, while the median overall survival was 38 months and progression-free survival was 9 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of preoperative mFOLFOX6 with short-course radiotherapy in patients with locally advanced rectal cancer and liver-only metastasis. Kim, KH., Shin, SJ., Cho, MS., et al.[2022]

The FORCE study is a phase II trial involving 130 patients with stage IV non-squamous non-small cell lung cancer, investigating the effects of nivolumab combined with hypofractionated palliative radiotherapy, aiming to assess its safety and efficacy in improving response rates and survival outcomes.

Preliminary data suggest that combining nivolumab with radiation therapy may enhance immune responses against tumors, potentially leading to better treatment outcomes compared to nivolumab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. Bozorgmehr, F., Hommertgen, A., Krisam, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04130854

INNATE: Immunotherapy During Neoadjuvant Therapy for ... INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer, a Phase II Randomized Multi-center Trial With and Without APX005M, an Anti-CD40 Agonist.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8003099/

Emerging Trends for Radio-Immunotherapy in Rectal Cancer In these trials, five-year recurrence rates for neo-adjuvant RT and CRT were 27% and 30% respectively, whereas OS rates were 74% and 70% [55].

3. pyxisoncology.com pyxisoncology.com/wp-content/uploads/publications/2021-11_sitc_poster-apx005m-011_innate_in-rectal_aguilera.pdf

Innate INNATE: Immunotherapy during neoadjuvant therapy for rectal cancer to elucidate ... • APX005M: Agonistic αCD40 Ab with FC mutation to enhance its agonistic.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03214250

Study Details | NCT03214250 | Safety and Efficacy of ... The main purposes of this study are to learn how effective the study drug combinations are in treating patients with metastatic pancreatic adenocarcinoma.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10767304/

A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab ... The 6.5-year survival rate for ipilimumab plus nivolumab approaches 50%, with a median overall survival (OS) of 72.1 months (1). The mechanisms responsible for ...

6. pyxisoncology.com pyxisoncology.com/wp-content/uploads/publications/2022-03_keystone_poster-apx005m-011_innate_in_rectal_aguilera.pdf

Elucidating factors of therapeutic response to ... Summary: • Rectal neoadjuvant approach: Excellent platform to test new RT immunotherapy combinations. • Combination of Sotigalimab with radiation and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11481156/

First-in-human clinical outcomes with NG-350A, an anti- ... This phase 1a study provided initial proof-of-mechanism for NG-350A, with strong evidence of tumor delivery, viral replication and transgene expression.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-05715

APX005M, mFOLFOX Chemotherapy, and Radiation ... The addition of APX005M to mFOLFOX (standard of care chemotherapy for rectal cancer) and radiation therapy may help improve response rates and long-term ...

9. aacrjournals.org aacrjournals.org/clincancerres/article/30/1/74/732080/A-Phase-II-Trial-of-the-CD40-Agonistic-Antibody

A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab ... The 6.5-year survival rate for ipilimumab plus nivolumab approaches 50%, with a median overall survival (OS) of 72.1 months (1). The mechanisms responsible for ...