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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of PR-104

Safety Issue:

Yes

Principal Investigator

Terri J. Melink, NP, MSN, ANP

Investigator Role:

Study Chair

Investigator Affiliation:

Proacta, Incorporated

Authority:

United States: Food and Drug Administration

Study ID:

PR104-1003

NCT ID:

NCT00459836

Start Date:

February 2007

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms

Name

Location

Proacta, IncorporatedSan Diego, California  92121