Clinical trial NCT01625260: A Study of ALT-801 in Patients With Bacillus Calmette-Guerin (BCG) Failure Non-Muscle Invasive Bladder Cancer
Official title: A Phase Ib/II Study of ALT-801 in Patients With Bacillus Calmette-Guerin (BCG) Failure Non-muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-muscle Invasive Bladder Cancer
Keywords: cancer
immunotherapy
targeted
non-muscle invasive
interleukin-2
antitumor
TCR
T-cell receptor
p53
p53 gene
p53 tumor supressor protein
urothelial cancer
bladder cancer
HLA-A2 positive
HLA-A*0201/p53 aa264-272
HLA complex
refractory
relapsed
BCG
multi-focal
carcinoma in situ
transitional cell carcinoma
gemcitabine
Lead sponsor: Altor BioScience
Sponsor class: INDUSTRY
Collaborators: name: James and Esther King Biomedical Research Program
First posted: 2012-06-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase Ib/II, open-label, multi-center and competitive enrollment study of ALT-801 combined with gemcitabine for patients who have BCG failure (defined as refractory, relapsing or intolerant), non-muscle invasive bladder cancer and refuse or are not medically fit to undergo a radical cystectomy recommended by the participating urologist as the standard next therapy per urologic guidelines. The purpose of this study is to confirm the safety and tolerability of a well-tolerated dose level of ALT-801, to determine the Recommended Dose level (RD) and characterize the immunogenicity of ALT-801 combined with gemcitabine in treated patients. The anti-tumor responses will also be assessed.

Detailed description: Bladder cancer is the fifth most common cancer in the United States with an estimated 71,000 new cases and approximately 14,000 deaths in 2009. Bladder cancer is also the costliest to treat per patient of all cancers, with annual direct medical expenditures in excess of $3.7 billion in the United States. This is largely because approximately 70% of all new cases of bladder cancer present as non-muscle invasive bladder cancer (NMIBC), which tends to recur, requiring repeated interventions and long-term follow-up.

Altor Bioscience Corp. has developed a tumor-targeted IL-2 fusion protein, ALT-801, comprising human recombinant IL-2 genetically linked to a TCR domain capable of binding a tumor associated human p53 peptide presented in the context of HLA-A2.

ALT-801 will be evaluated as to whether it can prevent disease progression and allow for bladder preservation to maintain the quality of life for patients with BCG failure, defined as refractory, relapsing or intolerant, non-muscle invasive bladder cancer who refuse or are not medically fit to undergo a radical cystectomy recommended by the participating urologist as the standard next therapy per urologic guidelines.

Eligibility criteria: ENTRY CRITERIA:

DISEASE CHARATERISTICS:

* Histologically confirmed high-risk (high grade Ta, T1 or carcinoma in situ, tumor \>4 cm or multi-focal) transitional cell carcinoma s/p TURBT with no remaining resectable disease within 4 weeks of study entry
* Intolerant of treatment with BCG or failure (refractory or relapsing) of at least one prior treatment with BCG
* Refuse or intolerant of a radical cystectomy
* No Evidence of regional and/or distant metastasis

PRIOR/CONCURRENT THERAPY:

* No concurrent radiotherapy, other chemotherapy, or other immunotherapy
* No scheduled radiotherapy, chemotherapy, other immunotherapy, or surgery before the scheduled response evaluation
* Must have recovered from side effects of prior treatments
* No concurrent use of other investigational agents

PATIENT CHARACTERISTICS:

Age

• ≥ 18 years

Performance Status

• ECOG 0, 1, or 2

Bone Marrow Reserve

* Absolute neutrophil count (AGC/ANC) ≥ 1,000/uL
* Platelets ≥ 100,000/uL
* Hemoglobin ≥ 8 g/dL

Renal Function

• Glomerular Filtration Rate (GFR) ≥ 50mL/min

Hepatic Function

* Total bilirubin ≤ 2.0 X ULN
* AST, ALT, ALP ≤ 3.0 X ULN

Cardiovascular

* No congestive heart failure \< 6 months
* No severe/unstable angina pectoris \< 6 months
* No myocardial infarction \< 6 months
* No history of ventricular arrhythmias
* No NYHA Class \> II CHF
* No uncontrollable supraventricular arrhythmias
* No history of a ventricular arrhythmia
* No other clinical signs of severe cardiac dysfunction
* Normal Transthoracic Echocardiogram (TTE) is required for patients who have history of EKG abnormalities, CHF, coronary artery disease or other cardiac disease, or have history of having received adriamycin or doxorubicin
* No patients with a left ventricular ejection fraction (LVEF) of less than 50%

Pulmonary

• Normal clinical assessment of pulmonary function

Other

* Negative serum pregnancy test if female and of childbearing potential
* Women who are not 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 uncontrollable CNS disease
* 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

Primary outcomes:
measure: Safety Profile
timeFrame: 12 weeks
measure: Disease Response Rate
timeFrame: From start of study treatment to up to 13 weeks
Secondary outcomes:
measure: Duration of Response
timeFrame: From confirmed complete response to up to 3 years
measure: Progression-free Survival
timeFrame: From start of study treatment to up to 3 years
measure: Event-free Survival
timeFrame: From start of study treatment to up to 3 years
measure: Overall Survival
timeFrame: From start of study treatment to up to 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Orlando
country: United States
facility: UF Health Center at Orlando Health
state: Florida
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
Study officials:
References: