Title
RAV12 in Treating Patients With Metastatic or Recurrent Adenocarcinoma
A Phase I, Multi-Dose Study of RAV12 (ANTI-RAAG12 MAB) in Patients With Metastatic or Recurrent Adenocarcinoma
Phase
Phase 1Lead Sponsor
MacroGenicsStudy Type
InterventionalStatus
Completed No Results PostedIndication/Condition
CancerIntervention/Treatment
rav12 ...Study Participants
53RATIONALE: Monoclonal antibodies, such as RAV12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of RAV12 in treating patients with metastatic or recurrent adenocarcinoma.
OBJECTIVES:
Determine the maximum tolerated dose of RAV12 in patients with metastatic or recurrent adenocarcinoma.
Determine the toxicity profile of this drug in these patients.
Determine the pharmacokinetics and immunogenicity of this drug in these patients.
Determine, preliminarily, the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive RAV12 IV over 2 hours 2-3 times per week in weeks 1-4 (course 1). Patients are evaluated for response on day 43. Patients achieving a partial or complete response may be eligible to receive additional courses of RAV12 as above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of RAV12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 15 additional patients are treated at the MTD in 1 or more patients groups (e.g., colorectal, pancreatic, gastroesophageal, and other adenocarcinoma).
After completion of study treatment, patients are followed within 4 weeks and then every 6-12 months thereafter.
PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.
Escalating doses of RAV12 (weekly 0.3, 1.0, 1.5, 3.0, 4.0, 5.0, 6.0 mg/kg or 0.5 mg/kg BIW or TIW; 0.75 mg/kg BIW) for 4 weeks
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma Metastatic or recurrent disease Not curable by standard therapies Must have failed at least 1, but no more than 3, prior therapies for metastatic or recurrent disease Patients with colorectal or breast adenocarcinoma must have failed at least 2 prior therapies Must have had at least stable disease for 3 months while on last treatment prior to most recent disease progression Meets 1 of the following criteria: At least 1 measurable site of disease ≥ 2 cm by radiography Evaluable disease that could be reliably and consistently followed, as deemed by the principal investigator RAAG12 expression confirmed* by immunohistochemistry NOTE: *Not required for patients with colon, pancreatic, or gastric adenocarcinoma No evidence of residual or recurrent CNS metastases Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Not specified Menopausal status Not specified Performance status ECOG 0-1 Life expectancy More than 3 months Hematopoietic Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL (transfusions allowed) Absolute neutrophil count ≥ 1,500/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN γ-glutamyl transferase ≤ 2.5 times ULN Adequate hepatic function sufficient to undergo study therapy Renal Creatinine < 1.5 mg/dL Adequate renal function sufficient to undergo study therapy Cardiovascular No New York Heart Association class III or IV heart disease No thrombosis within the past 3 months, including any of the following: Deep vein thrombosis Myocardial infarction Stroke Adequate cardiac function sufficient to undergo study therapy Pulmonary No pulmonary embolism within the past 3 months No significant pulmonary compromise, particularly dependence on supplemental oxygen on an as-needed or continuous basis Adequate pulmonary function sufficient to undergo study therapy Immunologic No active viral, bacterial or systemic fungal infection requiring parenteral therapy within the past 4 weeks No history of chronic or recurrent infection requiring continual antiviral, antifungal, or antibacterial agents No known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in study drug Other Amylase and lipase normal No other primary malignancy within the past 3 years except for the following: Treated non-melanoma skin cancer Carcinoma in situ of the cervix by biopsy Squamous intraepithelial lesion of the cervix by PAP smear Localized prostate cancer (Gleason score < 6) Resected melanoma in situ No other serious medical condition that would preclude study participation No dementia or altered mental status that would preclude giving informed consent Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 half-lives since prior monoclonal antibody therapy No concurrent vaccinations No concurrent prophylactic hematologic growth factors Chemotherapy At least 4 weeks since prior chemotherapy Endocrine therapy No concurrent steroids except for the following: Inhaled, ophthalmic, or nasal steroids Stable dose of oral prednisone (or equivalent) ≤ 10 mg/day Radiotherapy At least 4 weeks since prior radiotherapy Surgery More than 4 weeks since prior major surgery Other More than 4 weeks since prior investigational agents Prior oral antiviral, antifungal, or antibacterial therapy allowed provided therapy was completed within the past week No other concurrent antineoplastic therapy No concurrent immunosuppressive medications No other concurrent investigational agents No concurrent vitamins except those approved by the medical monitor Concurrent daily multivitamin allowed Concurrent bisphosphonates allowed provided patient is on stable dose for ≥ 1 month prior to study entry
