A Randomized, Double-Blind, Phase III Study of the Efficacy and Safety of Gemcitabine in Combination With TH-302 Compared With Gemcitabine in Combination With Placebo in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

Phase 3

Completed

• Conditions: adenocarcinoom van de pancreas; Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma

• Registration Number: NL-OMON40361
• Lead Sponsor: Merck

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

1. At least 18 years of age.
2. Ability to understand the purposes and risks of the trial and has signed a written informed consent form approved by the investigator*s Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
3. Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven by histology or cytology and previously untreated with chemotherapy or systemic therapy other than: radiosensitizing doses of 5-fluorouracil, radiosensitizing doses of gemcitabine if relapse occurred at least 6 months after completion of gemcitabine, neoadjuvant chemotherapy if relapse occurred at least 6 months after surgical resection or adjuvant chemotherapy if relapse occurred at least 6 months after completion of adjuvant chemotherapy.
4. Measurable disease (at least one target lesion outside of previous radiation fields) or non-measurable disease by RECIST 1.1 criteria.
5. Documentation of disease progression since any prior therapy.
6. ECOG performance status of 0 or 1. Two observers must assess performance status <=5 days prior to randomization. If discrepant, the poorer performance status is used.
7. Life expectancy of at least 3 months.
8. Acceptable liver function: bilirubin <=1.5 times upper limit of normal (ULN) (not applicable to subjects with Gilbert*s syndrome) and aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) <=3 times ULN (if liver metastases are present, then <=5 times ULN is allowed).
9. Acceptable renal function: serum creatinine <=1.5 times ULN or calculated creatinine clearance >=60 mL/min (Cockcroft-Gault formula).
10. Acceptable hematologic status (without growth factor support or transfusion dependency): absolute neutrophil count (ANC) >=1500 cells/µL, platelet count >=100,000/µL, hemoglobin >=9.0 g/dL.

Exclusion Criteria

1. New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction within 6 months prior to the date of randomization, unstable arrhythmia or symptomatic peripheral arterial vascular disease.
2. Symptomatic ischemic heart disease.
3. Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months).
4. Previous malignancy other than pancreatic cancer in the last 5 years, except for adequately treated non-melanoma skin cancer or pre-invasive cancer of the cervix.
5. Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia, or oxygen saturation <90% by pulse oximetry after a 2-minute walk) or in the opinion of the investigator any physiological state likely to cause systemic or regional hypoxemia.
6. Major surgery, other than diagnostic surgery, <=28 days prior to the date of randomization. Subject must have completely recovered from surgery.
7. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
8. Treatment of pancreatic cancer with radiation therapy or surgery <=28 days prior to the date of randomization.
9. Prior therapy with a hypoxic cytotoxin.
10. Subjects who participated in an investigational drug or device trial <=28 days prior to Day 1 of the first cycle.
11. Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
12. Subjects who have exhibited allergic reactions to a structural compound similar to TH-302 or the drug product excipients or to gemcitabine or its excipients.
13. Subjects who are taking medications that prolong QT interval and have a risk of Torsades de Pointes.
14. Subjects with a QTc interval calculated according to Bazett*s formula (QTc=QT/RR0.5; RR=RR interval) of >450 msec based on a screening electrocardiogram (ECG).
15. Subjects with a history of long QT syndrome.
16. Subjects taking a medication that is a moderate or strong inhibitor or inducer of CYP3A4.
17. Subjects taking a medication that is a sensitive substrate or substrates with a narrow
therapeutic index of CYP3A4, CYP2D6, or CYP2C9.
18. Subject is pregnant (positive serum beta human chorionic gonadotropin [β-HCG] test at screening) or is currently breast-feeding, anticipates becoming pregnant/impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessary, condoms, or diaphragm in conjunction with spermicidal gel, or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
19. Other significant concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this trial.
20. Unwillingness or inability to comply with the study protocol for any reason.
21. Legal incapacity or limited legal capacity.
22. Subjects with metastatic pancreatic cancer who are, according to Investigator*s assessment, suitable for FOLFIRINOX should be excluded from the trial (in countries in which FOLFIRINOX is considered as an acceptable therapeutic option). A subject who refuses - after being informed about all therapeutic alternatives - t

Study & Design

• Study Type: Interventional
• Study Design: Not specified