Clinical Trials /

A Study of DSP-0337 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile

NCT03416816

Description:

This is a Phase 1, open label, multi-center study of orally administered DSP-0337 in adult subjects with advance solid tumors that are refractory to standard treatment, or for whom no effective therapy exists.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of DSP-0337 in Patients With Advanced Solid Tumors to Determine the Safety and the Pharmacokinetic Profile
  • Official Title: A First-in-Human Phase I Trial to Determine the Safety and the Pharmacokinetic Profile of DSP-0337 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: BBI-DSP0337-101
  • NCT ID: NCT03416816

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
DSP-0337DSP-0337

Purpose

This is a Phase 1, open label, multi-center study of orally administered DSP-0337 in adult subjects with advance solid tumors that are refractory to standard treatment, or for whom no effective therapy exists.

Detailed Description

      The study is comprised of two parts: an initial dose escalation phase utilizing a 3 + 3
      design to determine maximum tolerated dose followed by a dose expansion cohort in
      approximately 40 additional subjects. Study participants will initially receive DSP-0337
      orally for 28 days (one cycle of treatment). If clinical benefit is seen, treatment can
      continue until disease progression.
    

Trial Arms

NameTypeDescriptionInterventions
DSP-0337ExperimentalIn Part 1 - Up to six dose levels will be investigated in dose-escalating cohorts to identify a maximum tolerated dose (MTD). An additional subset of patients will be treated to assess the effect of food intake on the PK of DSP-0337 administration at the MTD level. Once the recommended Phase 2 dose (RP2D) has been established, patients will be treated with the RP2D to explore preliminary antitumor activity and safety profile.
  • DSP-0337

Eligibility Criteria

        Inclusion Criteria

          1. Histologically or cytologically confirmed diagnosis of advanced cancer in patients
             with solid tumors that are refractory to standard treatment, or for whom no effective
             therapy exists.

          2. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
             0 to 1.

          3. Patients must be at least 18 years of age.

          4. Organ function must be adequate as follows:

               -  Bone Marrow Reserve: absolute neutrophil count ≥ 1.5 x 10^9/L; platelet count ≥
                  100 x 10^9/L; hemoglobin ≥ 9.0 g/dL. Must not have required blood transfusion
                  within 1 week of baseline blood count assessment.

               -  Hepatic: bilirubin < 1.5 times the upper limit of normal (ULN); alkaline
                  phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT) <
                  3.0 x ULN (AP, AST, and ALT < 5 x ULN is acceptable if the liver has tumor
                  involvement).

               -  Renal: serum creatinine within normal limits; for patients with levels above the
                  institutional normal value, the calculated corrected creatinine clearance must be
                  ≥ 60 mL/min/1.73 m^2 using the Cockcroft-Gault formula corrected for the body
                  surface area.

          5. Toxicities incurred as a result of previous anti cancer therapy (radiation therapy
             [RT], chemotherapy, or surgery) must be resolved to ≤ Grade 1 except for alopecia and
             anorexia.

          6. Patients must provide written informed consent.

          7. Female patients are eligible for the study if they meet the following criteria:

               -  Are not pregnant or nursing;

               -  Of non-childbearing potential defined as women who have had a hysterectomy,
                  bilateral oophorectomy, medically documented ovarian failure, or are documented
                  postmenopausal (follicle stimulating hormone > 40 mIU/mL); OR,

             Of childbearing potential defined as including women < 55 years of age, even those who
             have experienced 2 years of amenorrhea; all women should also meet both of the
             following criteria:

               -  A negative serum or urine pregnancy test during Screening,

               -  Sexually abstinent or correct and consistent use of one of the following methods
                  of birth control in addition to a male partner using a condom from Screening to 3
                  months after the last dose of study drug:

               -  hormone-containing contraceptive intrauterine device with a failure rate of < 1%
                  per year,

               -  cervical cap or diaphragm with a spermicidal agent,

               -  tubal sterilization, or

               -  vasectomy in male partner. Male patients must agree to sexual abstinence or to
                  consistently and correctly use a condom in combination with one of the above
                  methods of birth control from Screening to 3 months after the last dose of study
                  drug.

          8. Life expectancy must be ≥ 3 months.

        Exclusion Criteria

          1. Has received systemic anti-cancer therapy within the 3 weeks prior to starting the
             trial.

          2. Has received radiotherapy within the 28 days prior to first dose or within 12 weeks
             for patients with glioblastoma, with the exception of palliative radiotherapy to focal
             lesions for pain or other symptom control.

          3. Has received major surgery within the 4 weeks prior to starting the trial.

          4. Has significant inter-current illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             the study requirements.

          5. Clinically active known brain metastasis unless the brain metastases have been
             previously treated and are considered stable. Stable brain metastases are defined as
             no change on computed tomography (CT) scan or magnetic resonance imaging (MRI) for a
             minimum of 2 months and no change in steroid dose for a minimum of 4 weeks prior to
             starting the trial.

          6. Is pregnant or lactating.

          7. Had prior malignancy other than carcinoma in situ of the cervix or non-melanoma skin
             cancer, unless that prior malignancy was diagnosed and definitively treated at least 3
             years previously with no subsequent evidence of recurrence. If the patient has a
             medical history of a previous tumor that is not included in this criteria and that the
             Investigator feels is irrelevant for the objectives of the study, it should be
             evaluated with the Sponsor or Medical Monitor.

          8. Has a corrected QT interval (QTc) > 470 ms or has an electrocardiogram (ECG) with a
             new abnormal finding that is clinically significant.

          9. Has a known clinically significant GI disorder(s) including, but not limited to,
             inflammatory bowel disease or a history of extensive gastric resection and/or small
             intestinal resection.

         10. Has inability to take oral medications and/or has clinical or radiological diagnosis
             of bowel obstruction.

         11. Had prior treatment with napabucasin.

         12. Is not able to avoid the concomitant use of proton pump inhibitors (PPIs) or histamine
             H2-receptors antagonists, which have long-lasting pH-elevating effects, during
             DSP-0337 dosing, or avoid the use of antacids until at least 2 hours after dosing.

         13. Has a known history of human immunodeficiency virus (HIV) infection, active hepatitis
             B, or untreated hepatitis C; patients who have completed a course of antiviral
             treatment for hepatitis C are eligible.

         14. Has inability to comply with the protocol or study procedures.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose by assessing dose-limiting toxicities (DLTs)
Time Frame:4 weeks
Safety Issue:
Description:Dose escalating cohort

Secondary Outcome Measures

Measure:Number of Patients with Adverse Events
Time Frame:12 months
Safety Issue:
Description:Tolerability will be evaluated based on the adverse events (AEs) recorded at each contact with the patient, physical examinations, and the results of laboratory tests. Toxicity will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
Measure:Pharmacokinetics by assessing drug concentration in blood
Time Frame:4 weeks
Safety Issue:
Description:For food effect, dose escalating cohort
Measure:Urine excretion of napabucasin after DSP-0337 administration
Time Frame:24 hours
Safety Issue:
Description:Twenty four-hour urine will be collected and excretion of napabucasin will be evaluated.
Measure:Objective response rate (ORR)
Time Frame:6 months
Safety Issue:
Description:Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.
Measure:Time to progression (TTP)
Time Frame:6 months
Safety Issue:
Description:Defined as the time from first dose to the earlier date of assessment of progression by RECIST v1.1.
Measure:Progression free survival (PFS)
Time Frame:12 months
Safety Issue:
Description:Defined as the time from first dose to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v1.1.
Measure:Overall survival
Time Frame:12 months
Safety Issue:
Description:Measured from the date of first dose to the date of death by any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boston Biomedical, Inc

Trial Keywords

  • DSP-0337

Last Updated