Pancreatic Adenocarcinoma
Conditions
Keywords
Locally Advanced Unresectable Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma
Brief summary
The purpose of this study is to determine whether Gemcitabine versus Gemcitabine and TH-302 are effective in the treatment of subjects with first-line metastatic pancreatic adenocarcinoma.
Detailed description
A hypoxic microenvironment is a characteristic of many solid tumors including pancreatic cancer. The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to selectively physiologically target the hypoxic microenvironment. There is an absence of therapeutic options for subjects with metastatic pancreatic cancer. Gemcitabine provides clinical benefit as a single agent, but median survival is about 6 months. Combining gemcitabine with TH-302 may enable the targeting of both the normoxic and hypoxic regions of pancreatic cancer.
Interventions
1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.
DRUGTH-302
240 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.
Sponsors
PRA Health Sciences
ImmunoGenesis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. At least 18 years of age 2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee 3. Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven either by histology or cytology 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; * Adjuvant chemotherapy if relapse occurred at least 6 months after completion of adjuvant chemotherapy. 4. Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields) 5. Documentation of disease progression since any prior therapy 6. ECOG performance status of 0 or 1 7. Life expectancy of at least 3 months 8. Acceptable liver function: 1. Bilirubin less than or equal to 1.5 times upper limit of normal 2. AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times upper limit of normal (ULN); if liver metastases are present, then less than or equal to 5 times ULN is allowed 9. Acceptable renal function: a. Serum creatinine less than or equal to ULN 10. Acceptable hematologic status (without hematologic support): 1. ANC greater than or equal to 1500 cells/μL 2. Platelet count greater than or equal to 100,000/μL 3. Hemoglobin greater than or equal to 9.0 g/dL 11. All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose
Exclusion criteria
1. New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease 2. Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months) 3. Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years 4. 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 5. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery 6. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy 7. Treatment of pancreatic cancer with radiation therapy or surgery within 4 weeks prior to study entry 8. Prior therapy with an hypoxic cytotoxin 9. Subjects who participated in an investigational drug or device study within 28 days prior to study entry 10. Known active infection with HIV, hepatitis B, or hepatitis 11. Subjects who have exhibited allergic reactions to a structural compound, biological agent, or formulation (containing solutol and/or propylene glycol) similar to TH- 302 12. Females who are pregnant or breast-feeding 13. 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 study 14. Unwillingness or inability to comply with the study protocol for any reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle
Gemzar (Gemcitabine): 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle. | 69 |
| 240 mg/m2 TH-302 + Gemcitabine TH-302: 240 mg/m2 administered IV over 30 minutes Day 1, 8, and 15 of each 28-day cycle
Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle
Gemzar (Gemcitabine): 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.
TH-302: 240 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle. | 71 |
| 340 mg/m2 TH-302 + Gemcitabine TH-302: 340 mg/m2 of TH-302 be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle.
Gemcitabine: 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle
Gemzar (Gemcitabine): 1,000 mg/m2 administered IV over 30 minutes on Days 1, 8 and 15 of a 28-day cycle.
TH-302: 340 mg/m2 of TH-302 will be administered IV over 30 minutes on Days 1, 8 and 15 of every 28-day cycle. | 74 |
| Total | 214 |
Baseline characteristics
| Characteristic | Gemcitabine | 240 mg/m2 TH-302 + Gemcitabine | 340 mg/m2 TH-302 + Gemcitabine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 41 Participants | 28 Participants | 38 Participants | 107 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 43 Participants | 36 Participants | 107 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 62 Participants | 64 Participants | 67 Participants | 193 Participants |
| Sex: Female, Male Female | 29 Participants | 27 Participants | 32 Participants | 88 Participants |
| Sex: Female, Male Male | 40 Participants | 44 Participants | 42 Participants | 126 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 69 / 69 | 71 / 71 | 74 / 74 |
| serious Total, serious adverse events | 37 / 69 | 35 / 71 | 43 / 74 |
Outcome results
Primary
Progression-free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine | Progression-free Survival (PFS) | 111 days |
| 240 mg/m2 TH-302 + Gemcitabine | Progression-free Survival (PFS) | 169 days |
| 340 mg/m2 TH-302 + Gemcitabine | Progression-free Survival (PFS) | 183 days |