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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by Altor Bioscience Corporation
Information provided by (Responsible Party):
Altor Bioscience Corporation
ClinicalTrials.gov Identifier:
First received: March 30, 2011
Last updated: January 12, 2015
Last verified: January 2015

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
Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: Yes ]
  • Safety Profile [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment

  • Clinical Benefit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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: September 2015
Estimated Primary Completion Date: June 2015 (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
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326871

United States, Arizona
The University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Laura Pestana    520-694-9060    lpestana@uacc.arizona.edu   
Principal Investigator: Parminder Singh, MD         
United States, California
UCSD Moores Cancer Center Withdrawn
LaJolla, California, United States, 92093
United States, Florida
UF Health Center at Orlando Health Recruiting
Orlando, Florida, United States, 32806
Contact: Virginia Rizzo    321-841-4356    virginia.rizzo@orlandohealth.com   
Principal Investigator: Daniel Landau, M.D.         
Martin Health System Recruiting
Stuart, Florida, United States, 34994
Contact: Lucinda Fasig, RN    772-223-5945 ext 3776    lucinda.fasig@martinhealth.org   
Principal Investigator: Guillermo Abesada-Terk, Jr, M.D.         
H. Lee Moffitt Cancer Center and Research Institute Active, not recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Candy Wakwe, MEd    404-778-3448    candy.wakwe@emory.edu   
Contact: Jillian Ogden    404-778-4449    jbogden@emory.edu   
Principal Investigator: Wayne B Harris, M.D.         
United States, Illinois
Robert Lurie Comprehensive Cancer Center of Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Brandy Jackson-Davis    312-695-1357    brandy.jackson-davis@northwestern.edu   
Principal Investigator: Timothy Kuzel, M.D.         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Pamela Zehr, RN    319-353-8914    pamela-zehr@uiowa.edu   
Principal Investigator: Daniel A Vaena, M.D.         
United States, Kansas
University of Kansas Cancer Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Jan Ward, LPN, CCRP    913-558-4769    jward3@kumc.edu   
Principal Investigator: Peter VanVeldhuizen, M.D.         
United States, Louisiana
Louisiana State University Withdrawn
New Orleans, Louisiana, United States, 70112
United States, Michigan
Karmanos Cancer Center Completed
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Debra Hersan, RN    612-626-4495    herza001@umn.edu   
Principal Investigator: Gautam Jha, MD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Doug Cox    314-996-3452    dcox@dom.wustl.edu   
Principal Investigator: Joel Picus, MD         
United States, New York
University of Rochester Wilmont Cancer Center Recruiting
Rochester, New York, United States, 14642
Contact: Ayesha Khan    585-275-3351    Ayesha_Khan@urmc.rochester.edu   
Principal Investigator: Deepak M Sahasrabudhe, M.D.         
United States, North Carolina
Levine Cancer Institute Active, not recruiting
Charlotte, North Carolina, United States, 28203
United States, Oklahoma
University of Oklahoma Health Science Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Nancy Cleaver, RN    405-271-8770    nancy-cleaver@ouhsc.edu   
Contact: Tara Stine, RN    405-271-8001 ext 53481    tara-stine@ouhsc.edu   
Principal Investigator: Joel Slanton, MD         
United States, Pennsylvania
St. Luke's Hospital and Health Network Recruiting
Easton, Pennsylvania, United States, 18045
Contact: Rose Cabral    484-503-4151    cabralr@slhn.org   
Principal Investigator: Sanjiv S Agarwala, M.D.         
Thomas Jefferson University Hospital Active, not recruiting
Philadelphia, Pennsylvania, United States, 19107
UPMC Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Bethany Flaherty    412-623-8962    schnelbachb@upmc.edu   
Contact: Kristy Thompson, BSN, RN    814-676-7881    thompsonkl5@upmc.edu   
Principal Investigator: Rahul Parikh, MD         
Sponsors and Collaborators
Altor Bioscience Corporation
Study Chair: Hing C Wong, PhD Altor Bioscience Corporation
  More Information

No publications provided

Responsible Party: Altor Bioscience Corporation
ClinicalTrials.gov Identifier: NCT01326871     History of Changes
Other Study ID Numbers: CA-ALT-801-01-10
Study First Received: March 30, 2011
Last Updated: January 12, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Altor Bioscience Corporation:
urothelial cancer
combinational therapy
muscle invasive
T-cell receptor
p53 gene
p53 tumor supressor protein
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
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015