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

NCT ID: NCT00471562

Last Updated: 2017-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2009-10-31

Brief Summary

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.

Detailed 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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

therapeutic angiotensin-(1-7)

sequentially increasing doses 50-1000 mcg/kg

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

W. Jeffrey Petty, MD

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Locations

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

References

Petty WJ, Miller AA, McCoy TP, Gallagher PE, Tallant EA, Torti FM. Phase I and pharmacokinetic study of angiotensin-(1-7), an endogenous antiangiogenic hormone. Clin Cancer Res. 2009 Dec 1;15(23):7398-404. doi: 10.1158/1078-0432.CCR-09-1957. Epub 2009 Nov 17.

Reference Type: RESULT

PMID: 19920106 (View on PubMed)

Other Identifiers

CCCWFU-99206

Identifier Type: -

Identifier Source: secondary_id

CCCWFU-99206/Ang 1-7

Identifier Type: -

Identifier Source: secondary_id

CCCWFU-IRB00001136

Identifier Type: -

Identifier Source: secondary_id

CDR0000543744

Identifier Type: -

Identifier Source: org_study_id

NCT01581268

Identifier Type: -

Identifier Source: nct_alias