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

Neoplasms Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03416816
• Other study ID #: BBI-DSP0337-101
• Status: Terminated
• Phase: Phase 1
• Start date: May 15, 2018
• Est. completion date: June 15, 2020

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 30 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: June 15, 2020
• Est. primary completion date: June 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (BBI-608).

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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• DSP-0337
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.

Locations

Country	Name	City	State
United States	Karmos Cancer Center	Detroit	Michigan
United States	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	UT Heatlh San Antonio	San Antonio	Texas
United States	Utah Cancer Specialist	West Jordan	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.	Syneos Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory pharmacodynamic evaluation, including phosphorylated STAT3 (pSTAT3) expression level in patient-derived tumor tissue, as potential biomarkers		12 months
Primary	Maximum tolerated dose by assessing dose-limiting toxicities (DLTs)	Dose escalating cohort	4 weeks
Primary	Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs)	Dose escalating cohort	4 weeks
Secondary	Number of Patients with Adverse Events	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.	12 months
Secondary	Pharmacokinetics by assessing drug concentration in blood	For food effect, dose escalating cohort	4 weeks
Secondary	Urine excretion of napabucasin after DSP-0337 administration	Twenty four-hour urine will be collected and excretion of napabucasin will be evaluated.	24 hours
Secondary	Objective response rate (ORR)	Defined as the proportion of patients with a documented complete response or partial response (CR + PR) based on RECIST 1.1.	6 months
Secondary	Time to progression (TTP)	Defined as the time from first dose to the earlier date of assessment of progression by RECIST v1.1.	6 months
Secondary	Progression free survival (PFS)	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.	12 months