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

Proacta

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: docetaxel

Other: pharmacological study

Drug: gemcitabine hydrochloride

Drug: PR-104

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

Industry

Identifiers

NCT00459836

PROACTA-PR-104-1003

PROACTA-WIRB-20070094

PR104-1003

Details and patient eligibility

About

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.

Full 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.

Enrollment

42 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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