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

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Altor Bioscience Corporation Identifier:
First received: March 30, 2011
Last updated: April 11, 2016
Last verified: April 2016
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.

Condition Intervention Phase
Transitional Cell Carcinoma of Bladder
Urethra Cancer
Ureter Cancer
Malignant Tumor of Renal Pelvis
Drug: Cisplatin
Drug: Gemcitabine
Biological: ALT-801
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II Trial of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer

Resource links provided by NLM:

Further study details as provided by Altor Bioscience Corporation:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) and/or the recommended dose (RD) for dose expansion of ALT-801 in combination with cisplatin and gemcitabine or ALT-801 in combination with gemcitabine alone [ Time Frame: 8 weeks ]
  • Safety Profile [ Time Frame: 8 weeks ]
    Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment

  • Clinical Benefit [ Time Frame: 12 weeks ]
    Number of participants with an objective response, which includes, a complete response,a partial response or a stable disease

Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: 36 months ]
    Number of participants with, 6-month, 9-month, 12-month, 18-month, 24-month, 30-month, or 36-month progression-free survival.

  • Overall survival [ Time Frame: 36 months ]
    Number of participants with 6-month, 9-month, 12-month, 18-month, 24-month, 30-month or 36-month overall survival

  • Pharmacokinetics and immunogenicity [ Time Frame: 9 weeks ]

    Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-801 for patients enrolled up to the stage 1 expansion.

    Measures of anti-ALT-801 and IL-2 neutralizing antibodies

  • Tumor Typing [ Time Frame: 1 month ]
    Assess the relationship between the tumor presentation of HLA-A*0201/p53 aa 264-272 complexes and the safety and clinical benefits of study treatment

Estimated Enrollment: 90
Study Start Date: June 2011
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALT-801 with Cisplatin and Gemcitabine (Phase Ib and Phase II) Drug: Cisplatin
Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II): on day 1 of each course (if given)
Drug: Gemcitabine
Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II); on day 1 and 8 of each course
Biological: ALT-801
Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II): on day 3, 5, 8, and 12 of each course
Other Name: c264scTCR-IL2
Experimental: ALT-801 and Gemcitabine (Phase II only) Drug: Gemcitabine
Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II); on day 1 and 8 of each course
Biological: ALT-801
Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II): on day 3, 5, 8, and 12 of each course
Other Name: c264scTCR-IL2

Detailed 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


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No



  • 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


  • 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



  • ≥ 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


  • 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


  • Not receiving chronic medication for asthma
  • Normal clinical assessment of pulmonary function


  • No evidence of bleeding diathesis or coagulopathy


  • 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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01326871

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

Responsible Party: Altor Bioscience Corporation Identifier: NCT01326871     History of Changes
Other Study ID Numbers: CA-ALT-801-01-10
Study First Received: March 30, 2011
Last Updated: April 11, 2016

Keywords provided by Altor Bioscience Corporation:
combinational therapy
muscle invasive
T-cell receptor
p53 gene
p53 tumor supressor protein
urothelial cancer
bladder cancer
renal pelvis cancer
ureters cancer
urethra cancer
HLA-A2 positive
HLA-A*0201/p53 aa264-272
HLA complex
Muscle Invasive or Metastatic

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Ureteral Neoplasms
Urethral Neoplasms
Urinary Bladder Neoplasms
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Ureteral Diseases
Urologic Diseases
Urethral Diseases
Urinary Bladder Diseases
Kidney Diseases
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on May 24, 2017