We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04130854
Recruitment Status : Active, not recruiting
First Posted : October 18, 2019
Last Update Posted : July 18, 2022
Sponsor:
Collaborator:
Apexigen, Inc.
Information provided by (Responsible Party):
Todd Aguilera, University of Texas Southwestern Medical Center

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

Condition or disease Intervention/treatment Phase
Locally Advanced Rectal Adenocarcinoma Drug: APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days Drug: mFOLFOX and Radiation Therapy 5Gy x 5 days Phase 2

Detailed Description:
A phase II randomized trial 3:2 with short course radiotherapy followed by mFOLFOX chemotherapy prior to trans abdominal resection with or without an antiCD40 agonist antibody (APX005M). There will be continuous safety assessment for at least 6 patients. Planned accrual of 58 patients. An interim analysis after 30 patients have completed treatment and there will be early stopping criteria for futility or efficacy. Short course radiotherapy will consist of 5Gy x 5 to the pelvis and patients on APX005M arm will receive one infusion during radiotherapy course, have a two week break, then start FOLFOX with APX005M in conjunction with five out of six cycles of chemotherapy. Patients will be restaged and then undergo definitive surgery.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer, a Phase II Randomized Multi-center Trial With and Without APX005M, an Anti-CD40 Agonist
Actual Study Start Date : April 24, 2020
Estimated Primary Completion Date : November 1, 2023
Estimated Study Completion Date : November 1, 2023

Arm Intervention/treatment
Experimental: APX005M on day 3 of RT & day 3 of cycles 1-5 of mFOLFOX
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.
Drug: APX005M, mFOLFOX, and Radiation Therapy 5Gy x 5 days
  1. APX005M 0.3mg/kg intravenously on day 3 of radiation and on day 3 of cycles 1-5 of mFOLFOX
  2. Short course radiation therapy 5 Gy x 5 days
  3. Oxaliplatin 85mg/m2 intravenous day 1 of each cycle
  4. Leucovorin 400mg/m2 IV Day 1 of each cycle
  5. 5-FU 2400 mg/m2 continuous infusion over 46 hours of each cycle

Active Comparator: Radiation Therapy 5Gy x 5 days, mFOLFOX
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.
Drug: mFOLFOX and Radiation Therapy 5Gy x 5 days
  1. Short course radiation therapy 5 Gy x 5 days
  2. Oxaliplatin 85mg/m2 intravenous day 1 of each cycle
  3. Leucovorin 400mg/m2 IV Day 1 of each cycle
  4. 5-FU 2400 mg/m2 continuous infusion over 46 hours of each cycle




Primary Outcome Measures :
  1. Pathological Complete Response Rate [ Time Frame: At time of surgery ]
    The primary objective of this study is to determine the pathologic complete response (pCR) rate of the combined treatment modality.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 3 years ]
    To evaluate overall survival (OS), defined as the time between date of randomization and the date of death due to any cause.

  2. Toxicity analysis [ Time Frame: 3 years ]
    To evaluate toxicity analysis comparing the experimental from the standard arm measured according to CTCAE v5.0.

  3. Disease free survival [ Time Frame: 3 years ]
    To evaluate the disease free survival (DFS) and patterns of failure at three years. DFS is defined as the time between the date of definitive surgery and the first date of documented disease progression or death.


Other Outcome Measures:
  1. Exploratory Immunological Response [ Time Frame: 3 years ]
    To evaluate the immunologic response surrogates for patients tissue is obtained.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (<1cm from anal ring)
    • cT4 or within 3mm of MR fascia
    • Not candidate for sphincter preservation
    • Extramural venous invasion
  5. No prior treatment for rectal adenocarcinoma
  6. Eastern Cooperative Group (ECOG) performance status of 0-1.
  7. Laboratory values supporting acceptable organ and marrow function within 21 days of eligibility confirmation. Defined as follows:

    • WBC ≥ 3,000/mL;
    • ANC WBC ≥ 1,500/mL;
    • PLT ≥ 100,000/mL;
    • T Bili ≤ 1.5 x upper limit of normal (ULN);
    • AST/ALT ≤ 2.5 x ULN;
    • Creatinine ≤ 1.5 times upper limit of normal or calculated creatinine clearance > 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:

  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04130854


Locations
Layout table for location information
United States, Arizona
The University of Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, North Carolina
Wake Forest Baptist Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Apexigen, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Todd Aguilera, MD UT Southwestern Medical Center
Layout table for additonal information
Responsible Party: Todd Aguilera, Assistant Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04130854    
Other Study ID Numbers: STU 2019-1492
First Posted: October 18, 2019    Key Record Dates
Last Update Posted: July 18, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases