Trial to Evaluate Safety and Tolerability of GP-2250 in Combination With Gemcitabine

NCT03854110 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GP-2250-1001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

Brief Summary

This is a phase 1 first in human, dose escalation trial of GP-2250 administered in combination with gemcitabine in subjects with advanced pancreatic cancer previously treated with 5-fluorouracil-based chemotherapy. Prior radiosensitization with gemcitabine, the use of 5-fluorouracil, FOLFIRINOX or Nab-paclitaxel/gemcitabine in the neoadjuvant setting, and prior pancreaticoduodenectomy (Whipple procedure) is allowed. If prior treatment with gemcitabine was at therapeutic doses, a minimum of 3 months must have elapsed since the end of such treatment. As a precursor to 5-FU use of capecitabine-based chemotherapy is also permitted.

Conditions

Pancreatic Cancer, Adult

Keywords

Advanced disease; 5-fluorouracil

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  Dose Limiting Toxicity - dose at which toxicity causes cessation of dose escalations.

  12-24 months

Secondary Outcomes (2)

• Carbohydrate Antigen 19-9 (CA-19-9)

  12-24 months

• Effect on disease

  6-12 months

Study Arms (1)

GP-2250 Monotherapy

EXPERIMENTAL

GP-2250 in doses of 250 mg up to 30 grams intravenously on Days -7, 1, 8, 15 (Cycle 1) and Cycle 2 and all subsequent cycles on Days 7, 8, 15 of a 28-day cycle with gemcitabine 1000 mg/m2 on Days 1, 8, 15 days of the cycle.

Drug: GP-2250

Interventions

GP-2250 DRUG

GP-2250 monotherapy for pharmacokinetics and safety; GP-2250 plus gemcitabine for safety, tolerability, pharmacokinetics, and biomarker assessments

Also known as: gemcitabine

GP-2250 Monotherapy

Eligibility Criteria

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

You may qualify if:

• Informed Consent:
• Capable of giving signed informed consent as described in Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Male and female subjects age \> 18 years at the time of trial entry. Type of Subject and Disease Characteristics
• Histologically or cytologically confirmed advanced unresectable or metastatic pancreatic adenocarcinoma
• Subjects should be eligible to receive gemcitabine monotherapy for the treatment of their pancreatic cancer per the judgment of the Investigator
• Subjects must have documented disease progression while receiving or within 3 months of completing prior treatment with 5-fluorouracil-based chemotherapy.
• Subjects must have at least one RECIST Version 1.1 defined measurable tumor lesion
• Subjects must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
• Subjects with known central nervous system metastasis must have undergone brain targeted treatment and must be asymptomatic or radiographically and clinically stable (including not requiring steroids or anti-seizure medications) for at least 4 weeks prior to enrollment.
• All subjects must consent to provide archived tumor specimens for biomarker studies.
• Subjects must have adequate organ function as indicated by the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1,500 /mL
• Platelets ≥ 100,000 / mL
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN)

You may not qualify if:

• Diagnosis of any active malignancy other than pancreatic cancer within the past 2 years (not including non-melanoma skin carcinoma, ductal carcinoma in situ of the breast, or carcinoma in situ of uterine cervix treated with curative intent).
• Subjects has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonia or multiple allergies, clinically significant cardiovascular disease such as unstable angina, myocardial infarction, or acute coronary syndrome with \<=6 months prior to the start of study treatment, symptomatic or uncontrolled arrhythmia, congestive heart failure, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or ascites requiring paracentesis in the 4 weeks prior to Screening.
• Any other medical, psychiatric, or social condition deemed by the Investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate and participate in the trial, or which would interfere with the interpretation of the results.
• Subject has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
• Prior history or current signs of hyphema or glaucoma.
• History of sickle cell disease or hereditary non-spherocytic hemolytic anemia.
• Baseline QTc interval \>480 msec for female subjects or \>450 msec for male subjects.
• Subject is unwilling or unable to comply with study procedures or is planning to take a vacation for 7 or more consecutive days during the source of the study.
• First degree relative of the investigator, study staff or the sponsor.
• Positive test for SARS-CoV2 (COVID-19) by polymerase chain reaction (PCR) testing within one week prior to Screening.
• Any chemotherapy administered within 3 weeks or 5 half-lives (whichever is shorter) before first dose of GP-2250; other anti-cancer therapy (including surgery, radiotherapy, immunotherapy, hormone therapy, or targeted therapy) administered within 4 weeks or 5 half-lives (whichever is shorter) before the first dose of GP-2250; or within 6 weeks in the case of certain therapies (mitomycin C and nitrosoureas).
• Prior/Concurrent Clinical Trial Experience:
• Investigational therapy administered within 4 weeks or 5-half lives (whichever is shorter) before the first dose of GP-2250.

Sponsors & Collaborators

• Geistlich Pharma AG: lead
• Translational Drug Development: collaborator

Study Sites (5)

Hoag Family Cancer Institute

Newport Beach, California, 92663, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27292, United States

Location

Abramson Cancer Center at the University of Pennsylvania

Phildelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• Buchholz M, Majchrzak-Stiller B, Hahn S, Vangala D, Pfirrmann RW, Uhl W, Braumann C, Chromik AM. Innovative substance 2250 as a highly promising anti-neoplastic agent in malignant pancreatic carcinoma - in vitro and in vivo. BMC Cancer. 2017 Mar 24;17(1):216. doi: 10.1186/s12885-017-3204-x.

  PMID: 28340556 BACKGROUND

• Majchrzak-Stiller B, Buchholz M, Peters I, Waschestjuk D, Strotmann J, Hohn P, Hahn S, Braumann C, Uhl W, Muller T, Mohler H. GP-2250, a novel anticancer agent, inhibits the energy metabolism, activates AMP-Kinase and impairs the NF-kB pathway in pancreatic cancer cells. J Cell Mol Med. 2023 Jul;27(14):2082-2092. doi: 10.1111/jcmm.17825. Epub 2023 Jun 30.

  PMID: 37390227 BACKGROUND

• Kim MS, Glassman D, Handley KF, Lankenau Ahumada A, Jennings NB, Bayraktar E, Foster K, Joseph R, Lee S, Coleman RL, Sood AK. Mechanism and rational combinations with GP-2250, a novel oxathiazine derivative, in ovarian cancer. Cancer Med. 2024 Aug;13(15):e70031. doi: 10.1002/cam4.70031.

  PMID: 39114948 BACKGROUND

MeSH Terms

Conditions

Pancreatic cancer, adult

Interventions

Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Anup Kasi, MD

  University of Kansas

  STUDY CHAIR

Study Design

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

Model Details: 3+3 dose escalation

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: February 26, 2019
• Study Start: January 14, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)