Phase I Study of Oral DFP-11207 in Solid Tumors

NCT02171221 | Completed Phase 1

• 1 other identifier: D13-11038
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human, open label, single arm, sequential dose escalation and expansion study of oral DFP-11207 in patients with advanced solid tumors.

Conditions

Solid Tumors; Cancer

Keywords

Refractory or relapsed tumors; Antimetabolites, Antineoplastic; Fluorouracil

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of daily oral dosing of DFP-11207 in patients with solid tumors

  The MTD and tolerability will be based on the incidence of adverse events and dose-limiting toxicities in patients. CTCAE 4.0 will be used to grade the severity of adverse events.

  Continuous starting on day of first dose (Day 1) up to 30 days after last dose

• For food effect study: To assess PK profiles of DFP-11207 under fed and fasted conditions

  Plasma concentration and time data of DFP-11207 metabolites for the food effect study will be determined.

  Cycle 1, Day 1: pre dose, 4, 10, 24, and 48 hrs post-dose; Day 14: 2, 10 and 24 hrs post-dose; Day 16: pre-dose, 4, 10, and 24 hrs post-dose; Day 18: pre-dose; Day 23: 2 hrs post-dose; Day 29: 2 and 24 hrs post-dose. Cycle 2, Day 1: pre-dose

Secondary Outcomes (2)

• Pharmacokinetics (PK): To measure plasma and urine concentrations of DFP-11207 and its metabolites

  Cycle 1, Day 1: 1, 2, 4, 8, 12, 24 and 48 hours post-dose; and on Days 15 and 29

• To determine preliminary efficacy (overall response rate) in solid tumor patients receiving oral DFP-11207

  Every 8 weeks (2 months)

Study Arms (1)

Oral DFP-11207

EXPERIMENTAL

DFP-11207: daily oral dosing, 28 day treatment cycle

Drug: Oral DFP-11207

Interventions

Oral DFP-11207 DRUG

Oral DFP-11207

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically-confirmed solid tumors, refractory after standard therapy for the disease or for which conventional systemic chemotherapy is not reliably effective or no effective therapy is available.
• Aged ≥ 18 years.
• ECOG Performance Status of 0 or 1.
• Adequate clinical laboratory values defined as:
• absolute neutrophil count ≥ 1.5 x 10\^9/L
• platelets ≥ 100 x 10\^9/L
• plasma creatinine ≤ 1.5 x upper limit of normal (ULN) for the institution
• bilirubin ≤ 1.5 x ULN
• alanine transaminase (ALT) and aspartate transaminase (AST) \< 2.5 x ULN (\< 5 x ULN if documented hepatic metastases)
• Absence of uncontrolled intercurrent illnesses, including uncontrolled infections, cardiac conditions, or other organ dysfunctions.
• Patients may have measurable or non-measurable disease as defined by RECIST 1.1.
• Signed informed consent prior to the start of any study specific procedures.
• Women of child-bearing potential must have a negative serum or urine pregnancy test. Male and female patients must agree to use acceptable contraceptive methods for the duration of the study and for at least one month after the last drug administration.

You may not qualify if:

• Known allergy to fluoropyrimidines or known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Patients will be excluded if they have received previous chemotherapy, immunotherapy, radiotherapy or any other investigational therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or 5 half-lives for non-cytotoxic agents prior to this study entry.
• Extensive prior radiotherapy, more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation.
• Any concomitant condition that in the opinion of the Investigator could compromise the objectives of this study and the patient's compliance.
• Pregnant or lactating individuals.
• Current malignancies of another type, with the exception of adequately treated in situ cervical cancer, squamous cell and basal cell skin cancer or other malignancies with no evidence of disease for 2 years or more.
• Known history of HIV, HBV or HCV infection.
• Documented or known bleeding disorder.
• Requirement for anticoagulation treatment that increases international normalized ratio (INR) or activated partial thromboplastin time (aPTT) above the normal range (low dose deep vein thrombosis (DVT) or line prophylaxis is allowed).
• Clinically evident central nervous system metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment.
• Cardiac dysfunction defined as myocardial infarction within 6 months of study entry, New York Heart Association Class III or IV heart failure, uncontrolled dysrhythmias or poorly controlled angina.
• History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row), QTc ≥ 450 msec for men and 470 msec for women, or LVEF ≤ 40% by MUGA or ECHO.

Sponsors & Collaborators

• Delta-Fly Pharma, Inc.: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Ajani JA, Javle M, Eng C, Fogelman D, Smith J, Anderson B, Zhang C, Iizuka K. Phase I study of DFP-11207, a novel oral fluoropyrimidine with reasonable AUC and low Cmax and improved tolerability, in patients with solid tumors. Invest New Drugs. 2020 Dec;38(6):1763-1773. doi: 10.1007/s10637-020-00939-w. Epub 2020 May 6.

  PMID: 32377978 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

DFP-11207

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: June 19, 2014
• First Posted: June 24, 2014
• Study Start: June 1, 2014
• Primary Completion: September 13, 2018
• Study Completion: September 13, 2018
• Last Updated: January 29, 2019

Record last verified: 2019-01

Locations

US (1)