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

NCT03416816 | Terminated Phase 1 FDA Drug

• 1 other identifier: BBI-DSP0337-101
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Neoplasms

Keywords

DSP-0337

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose by assessing dose-limiting toxicities (DLTs)

  Dose escalating cohort

  4 weeks

• Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs)

  Dose escalating cohort

  4 weeks

Secondary Outcomes (6)

• Number of Patients with Adverse Events

  12 months

• Pharmacokinetics by assessing drug concentration in blood

  4 weeks

• Urine excretion of napabucasin after DSP-0337 administration

  24 hours

• Objective response rate (ORR)

  6 months

• Time to progression (TTP)

  6 months

Other Outcomes (1)

• Exploratory pharmacodynamic evaluation, including phosphorylated STAT3 (pSTAT3) expression level in patient-derived tumor tissue, as potential biomarkers

  12 months

Study Arms (1)

DSP-0337

EXPERIMENTAL

In 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.

Drug: DSP-0337

Interventions

DSP-0337 DRUG

DSP-0337 will be administered at the following doses in dose-escalation cohorts, maximum tolerated dose (MTD) for food effect, and recommended phase 2 dose (RP2D) for dose-expansion cohort. Dose 1: 200 mg once daily, Dose 2: 200 mg twice daily, Dose 3: 400 mg twice daily, Dose 4: 600 mg twice daily, Dose 5: 800 mg twice daily, Dose 6: 1000 mg twice daily.

DSP-0337

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Patients must be at least 18 years of age.
• 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.
• 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.
• Patients must provide written informed consent.
• 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:

You may not qualify if:

• Has received systemic anti-cancer therapy within the 3 weeks prior to starting the trial.
• 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.
• Has received major surgery within the 4 weeks prior to starting the trial.
• 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.
• 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.
• Is pregnant or lactating.
• 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.
• Has a corrected QT interval (QTc) \> 470 ms or has an electrocardiogram (ECG) with a new abnormal finding that is clinically significant.
• 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.
• Has inability to take oral medications and/or has clinical or radiological diagnosis of bowel obstruction.
• Had prior treatment with napabucasin (BBI-608).
• 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.
• 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.
• Has inability to comply with the protocol or study procedures.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead
• Syneos Health: collaborator

Study Sites (4)

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Karmos Cancer Center

Detroit, Michigan, 48201, United States

Location

UT Heatlh San Antonio

San Antonio, Texas, 78229, United States

Location

Utah Cancer Specialist

West Jordan, Utah, 84088, United States

Location

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: January 31, 2018
• Study Start: May 15, 2018
• Primary Completion: June 15, 2020
• Study Completion: June 15, 2020
• Last Updated: November 14, 2023

Record last verified: 2023-11

Locations

US (4)