A Phase Ib/II Trial of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer

CA-ALT-801-01-10

This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose-escalation study of ALT-801 in a biochemotherapy regimen either containing cisplatin and gemcitabine or containing gemcitabine alone in patients who have muscle invasive or metastatic urothelial cancer of bladder, renal pelvis, ureters and urethra. The purpose of this study is to evaluate the safety, determine the maximum tolerated dose (MTD) and the recommended dose (RD), and assess the anti-tumor response of ALT-801 in combination with cisplatin and gemcitabine or ALT-801 in combination with gemcitabine alone. The pharmacokinetic profile of ALT-801 in combination with cisplatin and gemcitabine will also be assessed. The study includes a dose escalation phase (Phase Ib) and a dose expansion phase (Phase II). Phase II has two treatment groups, Expansion Group 1 and Expansion Group 2. Expansion Group 2 is for platinum-refractory patients, consisting of two treatment arms based on the patient's renal function. Patients will enroll to Expansion Group 2 after stage 1 of the Group 1 expansion is complete.

2011-09-06

2016-04-11

2016-04-11

Completed

Early phase I

68

ENTRY CRITERIA: DISEASE CHARATERISTICS: * Muscle invasive or metastatic urothelial cancer of bladder, ureters, renal pelvis, and urethra * Histologically or cytologically confirmed with a clinical plan that would potentially include cisplatin\* plus gemcitabine systemic therapy or with disease refractory to a first-line platinum-based therapy (as defined in the protocol). \* Does not apply to patients screened for Phase II expansion * Surgically incurable PRIOR/CONCURRENT THERAPY: * No concurrent radiotherapy, other chemotherapy, or other immunotherapy * Must have recovered from side effects of prior treatments * If prior Proleukin® treatment, must have had a clinical benefit * No use of other investigational agents within 30 days of start or concurrently PATIENT CHARACTERISTICS: Age * ≥ 18 years Performance Status * ECOG 0 or 1 Bone Marrow Reserve * Absolute neutrophil count (AGC/ANC) ≥ 1,500/uL * Platelets ≥ 100,000/uL * Hemoglobin ≥ 10g/dL Renal Function * Glomerular Filtration Rate (GFR): * ≥ 50mL/min/1.73m\^2 for cisplatin-containing regimen * ≥ 40mL/min/1.73m\^2 for non-cisplatin-containing regimen Hepatic Function * Total bilirubin ≤ 1.5 X ULN * AST, ALT, ALP ≤ 2.5 X ULN, or ≤ 5.0 X ULN (if liver metastases exists) * PT INR ≤ 1.5 X ULN Cardiovascular * No congestive heart failure \< 6 months * No unstable angina pectoris \< 6 months * No myocardial infarction \< 6 months * No history of ventricular arrhythmias * No NYHA Class \> II CHF * Normal cardiac stress test required for subjects who are ≥ 50 years old, or have a history of EKG abnormalities, or have symptoms of cardiac ischemia or arrhythmia * No uncontrolled hypertension Pulmonary * Not receiving chronic medication for asthma * Normal clinical assessment of pulmonary function Hematologic * No evidence of bleeding diathesis or coagulopathy Other * Negative serum pregnancy test if female and of childbearing potential * No women who are pregnant or nursing * Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study * No known autoimmune disease other than corrected hypothyroidism * No known prior organ allograft or allogeneic transplantation * Not HIV positive * No active systemic infection requiring parenteral antibiotic therapy * No ongoing systemic steroid therapy required * No history or evidence of CNS disease (Controlled brain metastases treated with radiation therapy or surgery where the disease has been clinically stable for a period of a least 3 months before screening is allowed) * No psychiatric illness/social situation * No other illness that in the opinion of the investigator would exclude the subject from participating in the study * Must provide informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations

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2024-05-14