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

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This trial will consist of 2 parts. Phase 1 will use a Bayesian Optimal Interval (BOIN) dose escalation design of GP-2250 as intravenous single-dose monotherapy, followed by combination therapy with gemcitabine in subjects with advanced pancreatic cancer. A Simon Two-Stage Design (Phase 2) will follow this to assess preliminary clinical activity of GP-2250 in combination with gemcitabine at the recommended Phase 2 dose (RP2D) in subjects with advanced pancreatic cancer previously treated with FOLFIRINOX but never exposed to therapeutic gemcitabine

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Geistlich Pharma AG
• Collaborator: Translational Drug Development
• Treatments: Gemcitabine

Criteria

Inclusion Criteria:

Informed Consent:

1. 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.

Age:

2. Male and female subjects age > 18 years at the time of trial entry. Type of Subject and Disease Characteristics

3. Histologically or cytologically confirmed advanced unresectable or metastatic pancreatic adenocarcinoma

4. Subjects should be eligible to receive gemcitabine monotherapy for the treatment of their pancreatic cancer per the judgment of the Investigator

5. Subjects must have documented disease progression while receiving or within 3 months of completing prior treatment with FOLFIRINOX.

6. Subjects must have at least one RECIST Version 1.1 defined measurable tumor lesion

7. Subjects must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.

8. 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.

9. All subjects must consent to provide archived tumor specimens for biomarker studies.

10. Subjects must have adequate organ function as indicated by the following laboratory values:

1. Absolute neutrophil count (ANC) ≥ 1,500 /mL

2. Platelets ≥ 100,000 / mL

3. Hemoglobin ≥ 9 g/dL

4. Serum creatinine ≤ 1.5 X upper limit of normal (ULN)

5. Serum total bilirubin ≤ 1.5 × ULN

6. Aspartate aminotransferase (AST), (Serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT), and (Serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × ULN OR ≤ 5 × ULN for subjects with liver metastasis

7. International Normalized Ratio (INR) and/or Prothrombin Time (PT) ≤ 1.5 × ULN

8. Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 × ULN

9. Serum Albumin ≥ 3 gm/dL

11. Female subjects of childbearing potential (woman of childbearing potential [WOCBP]) must have a negative serum pregnancy test.

12. Subjects must use adequate contraception for the duration of the trial:

1. Male subjects must agree to use a highly effective contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 3 months after the last dose of trial intervention and refrain from donating sperm during this period

2. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

Not a WOCBP:

OR A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of trial intervention.

Exclusion Criteria:

Medical Conditions:

1. For Phase 2, 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).

2. 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.

Prior/Concomitant Therapy:

3. Prior exposure to gemcitabine (except when used as a radiosensitizer at least 6 months prior to enrollment).

4. 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:

5. Investigational therapy administered within 4 weeks before the first dose of GP-2250.