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PR-104 and Docetaxel or Gemcitabine in Treating Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00459836
Recruitment Status : Completed
First Posted : April 13, 2007
Last Update Posted : March 2, 2011
Information provided by:
Proacta, Incorporated

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as PR-104, docetaxel, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of PR-104 when given together with docetaxel or gemcitabine in treating patients with solid tumors.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: PR-104 Drug: docetaxel Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis Other: pharmacological study Phase 1

Detailed Description:



  • Determine the maximum tolerated dose of PR-104 in combination with docetaxel or gemcitabine hydrochloride in patients with solid tumors.


  • Determine the safety of PR-104 in combination with docetaxel or gemcitabine hydrochloride in these patients.
  • Determine the antitumor activity of these regimens using disease-specific parameters, such as exams, scans, and tumor markers, in these patients.
  • Determine the pharmacokinetics of PR-104 and its alcohol metabolite in these patients.
  • Determine the pharmacokinetics of docetaxel and gemcitabine hydrochloride when administered with PR-104.
  • Collect plasma samples for assessment of potential biomarkers of tumor hypoxia from these patients.
  • Examine metabolic changes in tumors using fludeoxyglucose F 18 positron emission tomography (PET) and PET imaging with fluoromisonidazole F 18 (a hypoxia-targeted radiopharmaceutical) in these patients.

OUTLINE: This is a nonrandomized, open-label, uncontrolled, multicenter, dose-escalation study of PR-104. Patients are assigned to 1 of 2 treatment groups according to patient's malignancy and prior treatment history.

  • Group 1: Patients receive docetaxel IV over 60 minutes and PR-104 IV over 60 minutes on day 1.
  • Group 2: Patients receive gemcitabine hydrochloride IV over 30 minutes and PR-104 IV over 60 minutes on days 1 and 8.

In both groups, treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients in each group receive escalating doses of PR-104 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Blood is collected at baseline and periodically during course 1 for pharmacokinetic analysis. Plasma samples are analyzed for biomarkers of tumor hypoxia at baseline and on days 2 and 8.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Multi-Center, Open-Label, Dose Escalation Trial of Intravenous PR-104 Given in Combination With Docetaxel or Gemcitabine in Subjects With Solid Tumors
Study Start Date : February 2007
Primary Completion Date : October 2009

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Maximum tolerated dose of PR-104

Secondary Outcome Measures :
  1. Safety of PR-104 as measured by CTCAE v3.0 criteria
  2. Dose-limiting toxicity of PR-104
  3. Pharmacokinetics of PR-104 and its alcohol metabolite in the blood
  4. Pharmacokinetics of gemcitabine and docetaxel in the presence of PR-104
  5. Antitumor activity

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed solid tumor malignancy
  • Treatment with either docetaxel or gemcitabine hydrochloride in combination with an investigational agent is reasonable
  • Measurable or evaluable disease


  • ECOG performance status of 0-1
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9.0 g/dL (red blood cell transfusion allowed)
  • Bilirubin normal
  • ALT and AST ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • PT/INR or aPTT ≤ 1.1 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 30 days after completion of study therapy
  • No evidence of any other significant medical disorder, including uncontrolled infection or infection requiring a concurrent parenteral antibiotic, or laboratory finding that, in the opinion of the investigator, would preclude study compliance
  • No known HIV positivity
  • No hepatitis B surface antigen positivity
  • No hepatitis C positivity with abnormal liver function test


  • No prior radiotherapy to > 25% of bone marrow
  • No prior high-dose chemotherapy (including conditioning for either myeloablative or nonmyeloablative transplantation)
  • No more than 3 prior chemotherapy regimens
  • More than 4 weeks since prior major surgery
  • More than 4 weeks since prior investigational or traditional anticancer therapy (including radiotherapy) (6 weeks for nitrosoureas and mitomycin C)
  • The following medications/treatments are not permitted during the trial:

    • Any other licensed or investigational anticancer treatment
    • Prophylactic hematopoietic growth factors
    • Irradiation therapy (palliative or therapeutic) unless given in the absence of tumor progression
  • Concurrent systemic steroids allowed provided the patient is on a stable dose for ≥ 2 weeks prior to study treatment
  • Concurrent androgen-deprivation therapy allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00459836

United States, California
Proacta, Incorporated
San Diego, California, United States, 92121
New Zealand
University of Auckland Cancer Center
Auckland, New Zealand
Waikato Hospital
Hamilton, New Zealand, 2020
Sponsors and Collaborators
Proacta, Incorporated
Study Chair: Terri J. Melink, NP, MSN, ANP Proacta, Incorporated

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Brenda Gibson, Assoc. Director, Proacta, Inc. Identifier: NCT00459836     History of Changes
Other Study ID Numbers: PR104-1003
First Posted: April 13, 2007    Key Record Dates
Last Update Posted: March 2, 2011
Last Verified: February 2011

Keywords provided by Proacta, Incorporated:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators