Immunotherapy + Chemoradiation for Rectal Cancer

Recruiting at 4 trial locations

Overseen By Brendan Paulman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

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

58 Participants Needed

Trial Summary

What is the purpose of this trial?

Determine the complete pathologic complete response (pCR) rate in patients with locally advanced rectal adenocarcinoma.

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.

What data supports the effectiveness of the treatment Immunotherapy + Chemoradiation for Rectal Cancer?

Research shows that using mFOLFOX6 (a combination of chemotherapy drugs) with radiation therapy can lead to better responses in rectal cancer patients, including higher rates of complete tumor disappearance. Additionally, combining chemotherapy with radiation before surgery is considered a standard approach for improving outcomes in advanced rectal cancer. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemoradiation generally safe for humans?

The safety of advanced radiotherapy techniques like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) has been studied in prostate cancer, showing some risk of late gastrointestinal (GI) and genitourinary (GU) toxicities, with 4.8% and 24% of patients experiencing these effects, respectively. These findings suggest that while these techniques are generally safe, there are potential risks of side effects. ^{6 7 8 9 10}

How is the treatment of Immunotherapy + Chemoradiation for Rectal Cancer different from other treatments?

This treatment combines immunotherapy with chemoradiation, using mFOLFOX chemotherapy and advanced radiation techniques like IMRT (intensity-modulated radiotherapy) to potentially enhance the immune response against cancer, which is a novel approach compared to traditional treatments that do not typically integrate immunotherapy. ^{11 12 13 14 15}

Research Team

Todd Aguilera, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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 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]

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]

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]

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]

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]

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]

References

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

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

2. Ireland 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. [2022]

3. United States 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. [2019]

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

Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. [2020]

5. United States 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. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity after moderately hypofractionated versus conventionally fractionated prostate radiotherapy: A systematic review and meta-analysis of the current literature. [2021]

7. Canada pubmed.ncbi.nlm.nih.gov

Early Experiences of Image Guided Prostate and Pelvic Nodal Irradiation With Intensity Modulated Radiation Treatment in Localized Prostate Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy. [2021]

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

Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate. [2022]

10. Japan 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. [2018]

11. Australia pubmed.ncbi.nlm.nih.gov

Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Intensity-modulated Radiotherapy for Anal Cancer: Dose-Volume Relationship of Acute Gastrointestinal Toxicity and Disease Outcomes. [2019]

13. England 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. [2020]

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

High-dose per Fraction Radiotherapy Induces Both Antitumor Immunity and Immunosuppressive Responses in Prostate Tumors. [2022]

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

Intensity-modulated radiation therapy for anal malignancies: a preliminary toxicity and disease outcomes analysis. [2022]