IL-2 Induced Hypotension Clinical Trial
Official title:
Phase I/II Open Label Dose Escalation and Double-Blind, Placebo-Controlled Evaluation of M40403, for the Prevention of the Dose Limiting Toxicities of High Dose IV Bolus IL-2 Treatment of Metastatic Melanoma or Renal Cell Carcinoma.
| Verified date | May 2002 |
| Source | MetaPhore Pharmaceuticals |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | United States: Food and Drug Administration |
| Study type | Interventional |
The clinical use of IL-2 is currently limited by development of dose-dependent hypotension (systolic blood pressure (SBP) < 90 mm Hg). The overall outcome is constant across sites with 20-50% of the patients requiring ICU management because of unresponsive hypotension and hyporeactivity (loss of response to vasoconstrictors). Because of the dose-limiting side effects, the duration of IL-2 dosing is frequently curtailed. Thus, hemodynamic toxicities have limited the usefulness of IL-2 therapy. M40403 has prevented both the hypotension and hyporeactivity associated with IL-2 treatment in preclinical studies. This trial will study the safety and efficacy of M40403 in the prevention or reduction of hypotension in patients receiving IL-2 therapy.
| Status | Suspended |
| Enrollment | 48 |
| Est. completion date | |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Patient has given signed informed consent. - Patient has documented histologically confirmed malignant melanoma or renal cell carcinoma which is metastatic. - Patient is eligible for high dose IV IL-2 therapy. - Tumor dimension of at least one lesion is measurable in two dimensions. - Patient is at least 18 years of age. - Patient is ambulatory with good performance status (ECOG PS 0,1; Karnofsky 100-70%). - If the patient is a woman of child bearing potential, patient is not lactating and ahs a negative pregnancy test (beta-HCG test obtained within 72 hours of enrollment) and agrees to use an adequate method of contraception for the duration of the study. - Patient has adequate organ function as defined by: - WBC count >3,500 per cubic millimeter; platelet count> 100,000 per cubic millimeter; - Bilirubin within institutional normal range; creatinine less than or equal to 2.0 mg/dl or creatinine clearance > 50 ml/min; - No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias or evidence of prior myocardial infarction. A pretreatment cardiac stress test must be performed within 42 days of IL-2 treatment. Patients with documented ischemia on the pretreatment cardiac stress test will be excluded from the study; - Adequate pulmonary reserve. Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment and an FEV1 > 2.0 liters or 75% of predicted for height and age is the minimum acceptable criteria for patient entry. PAtients unable to perform PFTs will be excluded from the study. - Patient has recovered from all toxic effects of prior therapy. - Patient has a life expectancy, in the opinion of the investigator, of at least 4 months. Exclusion Criteria: - Patient has an organ allograft. - Patient has brain metastases. A Brain CT or MRI scan should be performed within 42 days of IL-2 treatment. - Patient is know to be HIV antibody positive. HIV testing is not required for enrollment into this study. - Patient has evidence of active infection which requires antibiotic therapy. - Patient has received systemic corticosteroids in the four weeks prior to the first dose of study drug, or requires or is anticipated to require corticosteroids for intercurrent disease. - Patient has received radiotherapy, chemotherapy, or immunotherapy in the four weeks prior to the first dose of study drug, or is scheduled to receive concurrent radiotherapy, chemotherapy, or immunotherapy. - Patient has contraindication to treatment with pressor agents. - Patient currently receives chronic medication for asthma. - Patient has a history of another malignancy other than basal cell skin cancer within 5 years prior to the first dose of study drug. - Patient has any significant medical disease other than the malignancy which, in the opinion of the investigator, may interfere with completion of the study. - Patient has previously received any IL-2 therapy. - Patient has received another investigational medication within 4 weeks prior to M40403 administration or is scheduled to receive an investigational drug other than M40403 during the course of the study. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| United States | Northwestern University Medical School | Chicago | Illinois |
| United States | Providence Portland Medical Center | Portland | Oregon |
| United States | Huntsman Cancer Institute | Salt Lake City | Utah |
| Lead Sponsor | Collaborator |
|---|---|
| MetaPhore Pharmaceuticals |
United States,