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

Sponsor:	Proacta, Incorporated
Information provided by:	Proacta, Incorporated
ClinicalTrials.gov Identifier:	NCT00459836

Purpose

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	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: PR-104 Drug: docetaxel Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis Other: pharmacological study	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Gemcitabine Docetaxel Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by Proacta, Incorporated:

Primary Outcome Measures:

Maximum tolerated dose of PR-104 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety of PR-104 as measured by CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
Dose-limiting toxicity of PR-104 [ Designated as safety issue: Yes ]
Pharmacokinetics of PR-104 and its alcohol metabolite in the blood [ Designated as safety issue: No ]
Pharmacokinetics of gemcitabine and docetaxel in the presence of PR-104 [ Designated as safety issue: No ]
Antitumor activity [ Designated as safety issue: No ]

Enrollment:	42
Study Start Date:	February 2007
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459836

Locations

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

Investigators

Study Chair:

Terri J. Melink, NP, MSN, ANP

Proacta, Incorporated

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Brenda Gibson, Assoc. Director, Proacta, Inc.
ClinicalTrials.gov Identifier:	NCT00459836 History of Changes
Other Study ID Numbers:	PR104-1003, PROACTA-PR-104-1003, PROACTA-WIRB-20070094
Study First Received:	April 11, 2007
Last Updated:	February 28, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Proacta, Incorporated:

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms
Gemcitabine
Docetaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents

Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on February 09, 2012