Clinical Trials /

Study of CRX100 in Patients With Advanced Solid Tumors

NCT04282044

Description:

This clinical study is an open-label, phase 1, dose-escalation study to determine the safety, tolerability, and pharmacokinetic (PK) properties of CRX100 in adult subjects with advanced solid tumors. Patients will be screened and evaluated to determine whether or not they meet stated inclusion criteria. Enrolled subjects will undergo leukapheresis to enable the ex vivo generation of autologous cytokine induced killer (CIK) cells. Patients with triple-negative breast cancer, colorectal cancer, hepatocellular carcinoma, osteosarcoma, epithelial ovarian cancer, and gastric cancer will be considered.

Related Conditions:
  • Breast Adenocarcinoma
  • Colorectal Adenocarcinoma
  • Gastric Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Ovarian Epithelial Tumor
  • Osteosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of CRX100 in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1, Open-Label, Dose-Escalation Study of CRX100 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CRX100-001
  • NCT ID: NCT04282044

Conditions

  • Solid Tumor, Adult
  • Triple Negative Breast Cancer
  • Colorectal Cancer
  • Hepatocellular Carcinoma
  • Osteosarcoma
  • Epithelial Ovarian Cancer
  • Gastric Cancer

Interventions

DrugSynonymsArms
CRX100 suspension for infusionDose Escalation

Purpose

This clinical study is an open-label, phase 1, dose-escalation study to determine the safety, tolerability, and pharmacokinetic (PK) properties of CRX100 in adult subjects with advanced solid tumors. Patients will be screened and evaluated to determine whether or not they meet stated inclusion criteria. Enrolled subjects will undergo leukapheresis to enable the ex vivo generation of autologous cytokine induced killer (CIK) cells. Patients with triple-negative breast cancer, colorectal cancer, hepatocellular carcinoma, osteosarcoma, epithelial ovarian cancer, and gastric cancer will be considered.

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalDose escalation cohort for treatment of solid tumors that are relapsed, refractory or intolerant to standard care, or refusing standard therapies.
  • CRX100 suspension for infusion

Eligibility Criteria

        Inclusion Criteria:

        Subjects must meet all of the following criteria to be enrolled in this study:

          1. Age ≥18 years at the time of consent.

          2. Written informed consent in accordance with national, local, and institutional
             guidelines obtained prior to any study procedures.

          3. Subjects must have histologically-confirmed diagnosis of one of the following tumors:
             triple negative adenocarcinoma of the breast (human epidermal growth factor receptor
             2- estrogen receptor- and progesterone receptor- negative [HER2-/ER-/PR-]),
             adenocarcinoma of the colon or rectum (CRC), hepatocellular carcinoma (HCC),
             osteosarcoma, epithelial ovarian cancer, or gastric cancer. Documentation of the
             diagnosis with the original pathology report, or a recent biopsy, is required.

          4. Subjects must have relapsed disease or be refractory or intolerant to standard care,
             or refusing standard therapies.

          5. Subjects must have iRECIST evaluable disease using computed tomography (CT) or
             magnetic resonance imaging (MRI) with IV contrast , with at least one measurable
             target lesion.

          6. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0-2.

          7. Subjects must have recovered from the effects of recent surgery, radiation therapy, or
             chemotherapy.

          8. Subjects must be free of active infections requiring treatment doses of antibiotics,
             antifungals, or antiviral medications.

          9. No cellular therapy to be administered for at least 12 weeks prior to apheresis.

         10. Adequate hematologic function at the time of screening, defined as: absolute
             lymphocyte count (ALC) >500 cells/mm3, absolute neutrophil count (ANC) >750 cells/mm3,
             hemoglobin >8 g/dL, and platelet count >50,000 cells/mm3. Hemoglobin and platelet
             count thresholds must be achievable without transfusion of red blood cells or
             platelets.

         11. Adequate organ function, defined as:

               1. Renal function: serum creatinine <1.5x institutional upper limit of normal (ULN)
                  or calculated creatinine clearance >50 mL/min

               2. Adequate hepatic function: total bilirubin ≤1.5x institutional upper limit of
                  normal; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x
                  institutional upper limit of normal, unless liver metastases are present, in
                  which case it must be ≤5x ULN; International Normalized Ratio (INR) ≤1.5. For
                  subjects with HCC, adequate hepatic function is defined as: total bilirubin ≤3x
                  institutional upper limit of normal, AST/ALT ≤5x institutional upper limit of
                  normal, INR ≤1.7, Child-Turcotte-Pugh score <8.

         12. Women of childbearing potential (defined as all women physiologically capable of
             becoming pregnant) must have negative serum ß-human chorionic gonadotropin (ß-HCG) or
             urine pregnancy test.

         13. Women of childbearing potential must agree to use highly effective methods of
             contraception throughout the study and for 6 months after the last dose of CRX100.

         14. Males who have partners of childbearing potential must agree to use an effective
             barrier contraceptive method throughout the study and for 6 months after the last dose
             of CRX100.

         15. Subjects must be willing to comply with all study procedures, requirements and
             follow-up examinations.

        Exclusion Criteria:

        Subjects who meet any of the following criteria will be excluded from participation in this
        study:

          1. Subjects with new or progressive brain metastasis. Subjects with treated brain
             metastases are eligible if there is no evidence of progression for at least 4 weeks
             after central nervous system-directed treatment, as ascertained by clinical
             examination and brain imaging (MRI or CT) during the screening period.

          2. Active or history of autoimmune disease (known or suspected). Exceptions are permitted
             for vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             condition requiring only hormone replacement, psoriasis not requiring systemic
             treatment, or conditions not expected to recur in the absence of an external trigger.

          3. Have a condition requiring systemic treatment with either corticosteroids (>10 mg
             daily prednisone or equivalent) or other immunosuppressive medications within 14 days
             prior to apheresis, and within 14 days prior to infusion. Inhaled or topical steroids
             and adrenal replacement doses (≤10 mg daily prednisone equivalents) are permitted in
             the absence of active autoimmune disease. Short-term (<48 hr) steroid pretreatment for
             contrast allergy for imaging is permitted.

          4. Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C,
             life-threatening illnesses unrelated to cancer, or any serious medical or psychiatric
             illness that could, in the Investigator's opinion, interfere with participation in
             this study.

          5. Pregnant or nursing an infant (subject or household contacts).

          6. Clinically significant immunodeficiency (e.g., due to underlying illness and/or
             medication) in a subject or household contacts.

          7. Have any underlying medical condition (including, but not limited to, ongoing or
             active infection requiring treatment, symptomatic congestive heart failure, unstable
             angina pectoris, or cardiac arrhythmia), psychiatric condition, or social situation
             that, in the opinion of the Investigator, would compromise study administration as per
             protocol or compromise the assessment of AEs.

          8. Have a history of another invasive malignancy, except for the following circumstance:
             individuals with a history of invasive malignancy are eligible if they have been
             disease free and off treatment for at least 2 years or are deemed by the Investigator
             to be at low risk for recurrence of that malignancy; individuals with the following
             cancers are eligible if diagnosed and treated: carcinoma in situ of the breast, oral
             cavity, or cervix, localized prostate cancer, or basal cell or squamous cell carcinoma
             of the skin. When enrolling a subject with another malignancy, the Investigator should
             consider discussing the subject with the Medical Monitor.

          9. Treatment with any investigational drug study, oncolytic viral therapy or
             immunotherapy within three (3) weeks of enrollment.

         10. Chemotherapy three (3) weeks prior to infusion.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency of treatment-emergent Adverse Events and Dose Limiting Toxicities
Time Frame:28 days following dose administration for each dosed subject.
Safety Issue:
Description:The Primary Outcome Measure will be based on the frequency of treatment-emergent Adverse Events and Dose Limiting Toxicities during and after the administration of a single dose of the investigational drug.

Secondary Outcome Measures

Measure:Biodistribution of CRX100 based on subject's viral load as assessed through a viral shedding assay.
Time Frame:28 days following dose administration for each dosed subject.
Safety Issue:
Description:To characterize the biodistribution of CRX100 based on each subject's viral load as assessed through a viral shedding assay, following a single dose of investigational product.
Measure:Immune response to investigational drug based on subject's levels of neutralizing antibodies.
Time Frame:28 days following dose administration for each dosed subject.
Safety Issue:
Description:Levels of neutralizing vvDD antibodies will be summarized by dose level and time point following a single dose of investigational product.
Measure:Early anti-tumor activity of investigational drug based on iRECIST criteria
Time Frame:6 months after dose administration for each dosed subject.
Safety Issue:
Description:Summarized based on best response observed using RECIST classification of response. Overall response and frequencies of each level of response.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BioEclipse Therapeutics

Last Updated

April 2, 2021