Clinical trial NCT00471562: Angiotensin-(1-7) in Treating Patients With Metastatic or Unresectable Solid Tumors
Official title: Phase I Clinical Trial of Angiotensin 1-7 for Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 21 days
measure: Toxicity
timeFrame: 105 days
Secondary outcomes:
measure: Response rate (complete or partial response) as measured by RECIST criteria
timeFrame: 105 days
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: W. Jeffrey Petty, MD
role: STUDY_CHAIR
References:
citation: 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.