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A Randomized Cross-over Phase 2 Study of the Safety and Efficacy of Two Dose Levels of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma

Phase 2
18 Years
Open (Enrolling)
Pancreatic Adenocarcinoma

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Trial Information

A Randomized Cross-over Phase 2 Study of the Safety and Efficacy of Two Dose Levels of TH-302 in Combination With Gemcitabine Compared With Gemcitabine Alone in Previously Untreated Patients With Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma

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.

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

- 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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Safety Issue:


Principal Investigator

Mitesh Borad, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

June 2010

Completion Date:

January 2012

Related Keywords:

  • Pancreatic Adenocarcinoma
  • Locally Advanced Unresectable Pancreatic Adenocarcinoma
  • Metastatic Pancreatic Adenocarcinoma
  • Locally Advanced Unresectable or Metastatic Pancreatic Adenocarcinoma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous



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