AMP-224, a PD-1 Inhibitor, With Stereotactic Body Radiation Therapy in Metastatic Colorectal Cancer
Condition: Colorectal Cancer; Colorectal Neoplasms; Colorectal Carcinoma
MeSH terms: Colorectal Neoplasms
Intervention: AMP-224; Stereotactic Body Radiation Therapy(SBRT); Cyclophosphamide
Intervention description: 10mg/kg on day 1 then every 14 days for a total of 6 doses.; Dose Level 1: 8Gy x 1 day. Dose Level 2: 8Gy x 3 days; 200mg/m(2) IV on day 0.
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Anti-PD1 Therapy; Anti-Tumor Immunity; Liver Metastatic; B7-DC Fc Fusion Protein

Summary:

      Background:

      - T-cells are white blood cells that can find and kill germs and tumors. Cancer can keep
      T-cells from working. Researchers think a new drug called AMP-224 might help the T-cells in
      people with cancer. They think the drug might work even better when combined with a certain
      type of radiation therapy.

      Objective:

      - To study the safety and effectiveness of AMP-224 together with 1 or 3 days of stereotactic
      body radiation therapy (SBRT) directed to the liver.

      Eligibility:

      - People age 18 and older with metastatic colorectal cancer. Their cancer must have spread to
      the liver and not be responding to treatment.

      Design:

        -  Participants will be screened with a medical history, physical exam, and blood and urine
           tests. Their tumors will be measured with computerized tomography (CT) scans or magnetic
           resonance imaging (MRI) of the chest, stomach, and pelvis. They will have an
           electrocardiogram (ECG) heart test.

        -  Participants will have a small part of their tumor removed by needle (biopsy).

        -  Participants will have 8 study visits over about 10 weeks.

        -  At 1 visit, they will have another tumor biopsy.

        -  At 1 visit, they will get a chemotherapy drug through a vein (intravenous (IV)).

        -  At 6 visits, they will receive AMP-224 through an IV.

        -  At 1 or 3 visits, they will have SBRT. Computed tomography (CT) scans will map the
           position of their tumor. Radiation beams of different intensities at different angles
           will be directed to the tumor.

        -  At all visits, some screening procedures may be repeated.

        -  After treatment ends, participants will have 7 follow-up visits over about 5 months.
           Blood will be drawn. Some screening procedures may be repeated.
    

Eligibility criteria:

        -Inclusion Criteria

          1. Patients must have histopathological confirmation of Colorectal Carcinoma (CRC) by the
             Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this
             study.

          2. Patients must have progressed on or been intolerant of prior oxaliplatin and
             irinotecan containing chemotherapeutic regimen and have disease that is not amenable
             to potentially curative resection. Patients who have a known KRAS wild type tumor must
             have progressed or been intolerant to cetuximab or panitumumab-based chemotherapy.

          3. Patients must have one focus of metastatic disease in the liver that is amenable to
             stereotactic body radiation therapy (SBRT) in the opinion of radiation oncology.

          4. All patients enrolled will be required to have measurable disease by Response
             Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria outside the radiation field.

          5. Study patients must have disease that is amenable to pre and post treatment biopsy and
             be willing to undergo this.

          6. Age greater than or equal 18 years

          7. Life expectancy of greater than 3 months

          8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          9. Patients must have acceptable organ and marrow function as defined below:

               -  leukocytes less than or equal to 3,000/mcL

               -  absolute neutrophil count less than or equal 1,500/mcL

               -  platelets less than or equal 100,000/mcL

               -  total bilirubin greater than or equal 1.5X institution upper limit of normal

               -  Patients are eligible with alanine aminotransferase (ALT) or aspartate
                  aminotransferase (AST) measuring up to 5 x ULN given the presence of liver
                  metastasis.

               -  creatinine greater than 1.5X institution upper limit of normal

             Or

             -creatinine clearance less than or equal 45 mL/min/1.73 m(2), as calculated below, for
             patients with creatinine levels above institutional normal

         10. Patients must have recovered from any acute toxicity related to prior therapy,
             including surgery. Toxicity should be less than or equal to grade 1 or returned to
             baseline.

         11. Patients must not have other invasive malignancies within the past 3 years (with the
             exception of non-melanoma skin cancers, localized prostate cancer, carcinoma in situ
             of the cervix and non-invasive bladder cancer that has had successful curative
             treatment).

         12. Patient must be able to understand and willing to sign a written informed consent
             document.

        Exclusion Criteria

          1. Prior immune checkpoint inhibition with anti-programmed cell death-1 (PD1)/programmed
             death ligand-1(PD-L1) or anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) therapy or
             other specific T cell targeting agents.

          2. Patients who have had chemotherapy (or so-called targeted systemic therapy), large
             field radiotherapy, or major surgery must wait 4 weeks after completing treatment
             prior to entering the study.

          3. Patients with known brain metastases will be excluded from this clinical trial because
             of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          4. Uncontrolled intercurrent illness including, but not limited to, hypertension
             (systolic blood pressure (BP) greater than 160, diastolic BP greater than 100),
             ongoing or active systemic infection, symptomatic congestive heart failure, unstable
             angina pectoris, cardiac arrhythmia, uncontrolled diabetes or psychiatric
             illness/social situations that would limit compliance with study requirements.

          5. Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy
             are excluded from this study due to the possibility of pharmacokinetic interactions
             between antiretroviral medications and the investigational agent.

          6. History of chronic autoimmune disease (e.g., systemic lupus erythematosus or Wegener's
             granulomatosis, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's
             thyroiditis, hypophysitis, etc.) with symptomatic disease within the 3 years before
             randomization. Note: Active vitiligo or a history of vitiligo will not be a basis for
             exclusion. In addition, a past history of certain autoimmunity eg rheumatoid arthritis
             or thyroiditis may be allowed per principal investigator (PI) discretion provided it
             has been quiescent for a minimum of three years.

          7. Active or history of inflammatory bowel disease (colitis, Crohn's), irritable bowel
             disease, celiac disease, or other serious, chronic, gastrointestinal conditions
             associated with diarrhea.

          8. Dementia or significantly altered mental status that would prohibit the understanding
             or rendering of Information and Consent and compliance with the requirements of the
             protocol.

          9. Currently receiving immunosuppressive doses of steroids or other immunosuppressive
             medications (inhaled and topical steroids are permitted)

         10. History of sarcoidosis syndrome

         11. History of hypersensitivity reaction to human or mouse antibody products.

         12. Pregnancy and breast feeding are exclusion factors. The effects of AMP-224 on the
             developing human fetus are unknown. Enrolled patients must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry, the duration of study participation and 3 months after the end of the
             treatment. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately.

         13. Patients with unhealed surgical wounds for more than 30 days.

         14. Patients with known sensitivity or allergy to any components of AMP-224.