Angiotensin-(1-7) in Treating Patients With Metastatic or Unresectable Solid Tumors

Wake Forest University (WFU)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Biological: therapeutic angiotensin-(1-7)

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00471562

CDR0000543744

CCCWFU-IRB00001136

CCCWFU-99206

CCCWFU-99206/Ang 1-7

Details and patient eligibility

About

RATIONALE: Angiotensin-(1-7) may stop the growth of solid tumors by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of angiotensin-(1-7) in treating patients with metastatic or unresectable solid tumors.

Full description

OBJECTIVES:

Primary

Determine the maximum tolerated dose of therapeutic angiotensin-(1-7) in patients with metastatic or unresectable solid tumors.
Determine the pharmacokinetics of this drug in these patients.

Secondary

Determine tumor response in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive therapeutic angiotensin-(1-7) subcutaneously on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of therapeutic angiotensin-(1-7) 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 during the first 3 weeks of study therapy. At least 6 patients are treated at the MTD.

Blood samples are collected from patients after the first and fifth doses of the study drug for pharmacokinetic correlative studies.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Enrollment

18 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed advanced solid tumor meeting 1 of the following criteria:
- Metastatic disease
- Unresectable disease
Standard curative or palliative measures do not exist or are no longer effective
Measurable or nonmeasurable disease
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- Nonmeasurable disease, defined as all other lesions, including small lesions (i.e., ≥ 1 unidimensionally measurable lesion < 20 mm by conventional techniques or < 10 mm by spiral CT scan) and truly nonmeasurable lesions, including any of the following:
  - Bone lesions
  - Ascites
  - Pleural or pericardial effusion
  - Lymphangitis cutis or pulmonis
  - Abdominal masses not confirmed and followed by imaging techniques
  - Cystic lesions
No lung cancer with recent hemoptysis
No brain metastasis

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 4 weeks
No evidence of bleeding diathesis
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine clearance > 30 mL/min
Bilirubin < 2 mg/dL
AST and ALT < 3 times upper limit of normal
No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Uncontrolled hypertension or hypotension
No psychiatric illness or social situation that would preclude informed consent or study compliance

PRIOR CONCURRENT THERAPY:

At least 4 weeks since prior major surgery
At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for melphalan, nitrosoureas, or mitomycin C)
No concurrent therapeutic anticoagulation
No other concurrent investigational agents
No concurrent angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers
No concurrent combination antiretroviral therapy for HIV-positive patients