Bladder Cancer Clinical Trial

A Study of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer

Summary

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.

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Full Description

Bladder cancer is the fourth most common malignancy in men and the ninth most common in women in the US, with an estimated 68,810 new cases and 14,070 deaths for the year 2008. Approximately 90% to 95% of newly diagnosed patients are with transitional cell carcinomas (TCC). Approximately 20% to 25% contain advanced (muscle invasive or metastatic) disease. Muscle invasive bladder cancer is life threatening. Clinical trials have demonstrated that TCC is a chemotherapy-sensitive malignancy. Most current cancer treatment strategies involve the use of chemotherapeutic or biological drugs that have a low therapeutic ratio. The limitations are a consequence of effects of the therapeutic drug on normal tissues. One approach to control systemic exposure effects is to target the drug itself into the site of the tumor. For example, antibodies have been developed for use as tumor targeting agents and have had success in the clinic. However, despite the promise of antibody-based immunotherapy, there are limitations with these class of reagents. Even so, immunotherapy remains a promising approach to treat cancer.

One strategy that has received attention is treatment with cytokines such as IL-2 to enhance anti-tumor immunity. IL-2 has stimulatory effects on a number of immune cell types including T and B cells, monocytes, macrophages, lymphokine-activated killer cells (LAK) and natural killer (NK) cells. Based on the ability of IL-2 to provide durable curative anti-tumor responses, systemic administration of IL-2 has been approved to treat patients with metastatic melanoma or renal carcinoma. Unfortunately, the considerable toxicity associated with this treatment makes it difficult to achieve an effective dose at the site of the tumor and limits the population that can be treated. Thus, there is critical need for innovative strategies that enhance the effects of IL-2, to reduce its toxicity without compromising the clinical benefit, and to treat other diagnoses.

The study drug, ALT-801, is a biologic compound of interleukin-2 (IL-2) genetically fused to a humanized soluble T-cell receptor directed against the p53-derived peptides expressed on tumor cells. The p53 protein is one of the most important factors that protects from developing cancer and is also one of the most frequently mutated genes in many cancers, which include muscle-invasive bladder cancer. For any given cancer type, p53 dysfunction generally correlates with poor prognosis versus other the same site-of-origin. In some tumors, p53 mutation and over-expression also is associated with resistance to chemotherapy. This study is to further evaluate whether directing IL-2 activity using ALT-801 to the patient's tumor sites that over-express p53 results in clinical benefits

View Eligibility Criteria

Eligibility Criteria

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

Study is for people with:

Bladder Cancer

Phase:

Phase 1

Estimated Enrollment:

68

Study ID:

NCT01326871

Recruitment Status:

Completed

Sponsor:

Altor BioScience

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There are 16 Locations for this study

See Locations Near You

The University of Arizona Cancer Center
Tucson Arizona, 85724, United States
UF Health Center at Orlando Health
Orlando Florida, 32806, United States
Martin Health System
Stuart Florida, 34994, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa Florida, 33612, United States
Emory University
Atlanta Georgia, 30322, United States
Robert Lurie Comprehensive Cancer Center of Northwestern University
Chicago Illinois, 60611, United States
University of Iowa Hospitals and Clinics
Iowa City Iowa, 52242, United States
University of Kansas Cancer Center
Fairway Kansas, 66205, United States
Karmanos Cancer Center
Detroit Michigan, 48201, United States
University of Minnesota
Minneapolis Minnesota, 55455, United States
Washington University
Saint Louis Missouri, 63110, United States
Levine Cancer Institute
Charlotte North Carolina, 28203, United States
University of Oklahoma Health Science Center
Oklahoma City Oklahoma, 73104, United States
St. Luke's Hospital and Health Network
Easton Pennsylvania, 18045, United States
Thomas Jefferson University Hospital
Philadelphia Pennsylvania, 19107, United States
UPMC Cancer Center
Pittsburgh Pennsylvania, 15232, United States

How clear is this clinincal trial information?

Study is for people with:

Bladder Cancer

Phase:

Phase 1

Estimated Enrollment:

68

Study ID:

NCT01326871

Recruitment Status:

Completed

Sponsor:


Altor BioScience

How clear is this clinincal trial information?

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