Evaluation of M40403 for the Prevention of Dose Limiting Toxicities of High Dose IL-2

• Status: Suspended
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MetaPhore Pharmaceuticals

Criteria

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.