Clinical Trial Finder

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For RECTAL cancer, just diagnosed (no prior treatment allowed), Stage III, Stage II with high risk features or Stage IV with liver-limited disease (up to 3 lesions)
Possibility of receiving an immunotherapy (a CD40 Agonist) along with standard of care chemo-radiation)
Randomized.
-Arm 1: APX005M (immunotherapy) + Folfox + radiation, before surgery
-Arm 21: Folfox + radiation, before surgery
“APX005M: agonistic monoclonal antibody binds to CD40 on a variety of immune cell types. This triggers the cellular proliferation and activation of antigen-presenting cells (APCs), and activates B-cells, and effector and memory T-cells. This results in an enhanced immune response against tumor cells. APX005M also binds to and activates CD40 present on the surfaces of some solid tumor cells, leading to apoptosis and decreased tumor growth. CD40, a cell surface receptor and member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on various immune cells and certain cancer cells; it mediates both indirect tumor cell killing through the activation of the immune system and direct tumor cell apoptosis.”
APX005M is evaluated in several trials, one of them in combination with chemotherapy in pancreatic cancer, with encouraging early results (NCT03214250 )

Inclusion Criteria

Inclusion Criteria:

1. At least 18 years of age. Both men and women and members of all races and ethnic groups will be included.
2. Willing and able to provide written informed consent
3. Pathologic diagnosis of rectal adenocarcinoma
4. Stage III or Stage II with at least 1 of the following high-risk features:

* Distal ( 45 mL/min per Cockcroft-Gault equation.
8. Female participants of childbearing potential (FOCBP) must have a negative serum or urine pregnancy test (per institutional standards) within 72 hours prior to the start of study drug.

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.

FOCBP are those who have not been surgically sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or have not been free from menses for >1 year without an alternative medical cause.
9. Male participants must agree to use an adequate method of contraception (Appendix A) starting with the first dose of study therapy through 90 days after the last dose of study drugs.

Exclusion Criteria

Exclusion Criteria:

1. Distant nodal disease (retroperitoneal nodes) including inguinal nodes, or any metastatic disease by CT or PET
2. Prior RT to the pelvis.
3. Uncontrolled comorbid illness or condition including an active infection, congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness that would limit compliance with the study requirements.
4. Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
5. Any positive history for HIV/AIDS, HTLV, hepatitis B or hepatitis C virus indicating acute or chronic infection.
6. Any active known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
7. Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
8. Malignancy in the past 3 years that required active treatment except locally curable cancers or cancers deemed by the treating physicians to not impact the subject's survival duration.
9. Participants receiving any other investigational agent, standard antineoplastic agents, or immunosuppressive agents.
10. Known history of interstitial lung disease.
11. Received live vaccine within 6 weeks prior to randomization.
12. Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
13. Participants who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
14. Patient is not a candidate for the full treatment regimen.