Clinical Trials /

INNATE: Immunotherapy During Neoadjuvant Therapy for Rectal Cancer

NCT04130854

Description:

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

Related Conditions:
  • Rectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Randomized Multi-center Trial of Total Neoadjuvant Therapy With and Without CD40 Agonist, APX005M, for Locally Advanced Rectal Adenocarcinoma
  • Official Title: Phase II Randomized Multi-center Trial of Total Neoadjuvant Therapy With and Without CD40 Agonist, APX005M, for Locally Advanced Rectal Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: STU 2019-1492
  • NCT ID: NCT04130854

Conditions

  • Locally Advanced Rectal Adenocarcinoma

Interventions

DrugSynonymsArms
Radiation Therapy 5Gy x 5 daysAPX005MRadiation Therapy 5Gy x 5 days - APX005M 0.3ug/m^2 IV on day 3

Purpose

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

Detailed Description

      A phase II randomized trial 3:2 with continuous safety assessment for at least 6 patients.
      Interim analysis after 30 patients for early stopping criteria for futility or efficacy. The
      null hypothesis is that pCR is 16% and to reject the null hypothesis we aim to show a 48% pCR
      rate using a 5% one sided type 1 error boundary with 80% power. At interim analysis if the
      test statistic is less than or equal to 2.488 then the trial will be stopped with rejection
      of the null hypothesis. If the test statistic is less than or equal to 0.442 then we accept
      the null hypothesis and stop the trial early.
    

Trial Arms

NameTypeDescriptionInterventions
Radiation Therapy 5Gy x 5 days - APX005M 0.3ug/m^2 IV on day 3ExperimentalOn Day 1 of Cycles 1 and 2 of each mFOLFOX treatment, participants will receive another dose of APX005M. The sequence of administration of APX005M in combination with mFOLFOX. In Cycle 3, 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.
  • Radiation Therapy 5Gy x 5 days
Radiation Therapy 5Gy x 5 daysExperimentalParticipants 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.
  • Radiation Therapy 5Gy x 5 days

Eligibility 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)

               -  Bulky cT4 or within 3mm of MR fascia

               -  Not candidate for sphincter preservation

               -  Extramural venous invasion

          5. Stage IV liver-limited disease with ≤ 3 lesions Note: up to 6 participants with
             liver-limited disease are eligible to participate

          6. No prior treatment for rectal adenocarcinoma

          7. Eastern Cooperative Group (ECOG) performance status of 0-1.

          8. Laboratory values supporting acceptable organ and marrow function within 30 days of
             eligibility confirmation. Defined as follows:

               -  WBC ≥ 3,000/mL;

               -  ANC WBC ≥ 1,500/mL;

               -  PLT ≥ 50,000/mL;

               -  T Bili ≤ 1.5 x upper limit of normal (ULN);

               -  AST/ALT ≤ 2.5 x ULN;

               -  Creatinine not above ULN, or creatinine clearance ≥60 mL/min/1.73 m2 for
                  participants with creatinine levels above institutional normal.

          9. 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 6 months after the last dose of study drugs.

             FOCBP are those who have not been surgically sterilized or have not been free from
             menses for >1 year without an alternative medical cause.

         10. Male participants must agree to use an adequate method of contraception (Appendix A)
             starting with the first dose of study therapy through 3 months after the last dose of
             study drugs.

        Exclusion Criteria:

          1. Distant nodal disease (retroperitoneal nodes), or any metastatic disease by CT or PET
             (except liver limited disease as allowed in 4.1.5).

          2. Prior RT to the pelvis.

          3. Uncontrolled comorbid illness or condition including an 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. Participants receiving any other investigational or standard antineoplastic agents.

          9. Psychiatric illness/social situations that would limit consenting and compliance with
             study requirements.

         10. Participants who are pregnant or nursing due to the potential for congenital
             abnormalities and the potential of this regimen to harm nursing infants.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathological Complete Response Rate
Time Frame:3 years
Safety Issue:
Description:The primary objective of is to determine the pathologic complete response (pCR) rate of the combined treatment modality.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:3 years
Safety Issue:
Description:To evaluate overall survival (OS), defined as the time between date of randomization and the date of death due to any cause.
Measure:Disease-free Survival
Time Frame:3 years
Safety Issue:
Description:To evaluate disease-free survival (DFS), defined as the time between date of definitive surgery and the first date of documented disease progression, or death
Measure:Rate of resection
Time Frame:3 years
Safety Issue:
Description:To evaluate the rate of R0 resection, defined as a negative surgical margin at time of total mesorectal excision
Measure:Safety
Time Frame:3 years
Safety Issue:
Description:To evaluate the safety and tolerability of the study regimen, including acute and late toxicity as measured according to CTCAE v5.0.
Measure:Disease Recurrence
Time Frame:3 years
Safety Issue:
Description:To evaluate the rate of local failure, defined as recurrence of disease in the pelvis
Measure:Development of Disease
Time Frame:3 years
Safety Issue:
Description:To evaluate the rate of distant failure, defined as development of disease outside of the pelvis.
Measure:Clinical Imaging response
Time Frame:3 years
Safety Issue:
Description:To describe imaging response and clinical response from initial clinical stage to the clinical restaging evaluation prior to surgery which includes a noncontrast pelvic MRI.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

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