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Transitional Cell Carcinoma of BladderPhase 1/2NCT01326871

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

A Phase 1/2 study testing Cisplatin, Gemcitabine and ALT-801 in people with Transitional Cell Carcinoma of Bladder and Urethra Cancer, run by Altor BioScience at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cisplatin, Gemcitabine and ALT-801
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
16 sitesUnited States
Study dates
6 Sep 2011to 11 Apr 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Robert Lurie Comprehensive Cancer Center of Northwestern University

    Chicago, Illinois, 60611

  • Karmanos Cancer Center

    Detroit, Michigan, 48201

  • St. Luke's Hospital and Health Network

    Easton, Pennsylvania, 18045

  • University of Kansas Cancer Center

    Fairway, Kansas, 66205

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • University of Oklahoma Health Science Center

    Oklahoma City, Oklahoma, 73104

  • UF Health Center at Orlando Health

    Orlando, Florida, 32806

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • UPMC Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Washington University

    St Louis, Missouri, 63110

  • Martin Health System

    Stuart, Florida, 34994

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85724

Other trials in United States

About this study

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

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.

Read the 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

Being tested
Cisplatin, Gemcitabine, ALT-801
Keywords
cancer, immunotherapy, immunochemotherapy, combinational therapy, targeted, metastatic, muscle invasive, interleukin-2, cisplatin, gemcitabine, antitumor, TCR, T-cell receptor, p53, p53 gene, p53 tumor supressor protein, urothelial cancer, bladder cancer, renal pelvis cancer, ureters cancer
Medical subject headings
Urethral Neoplasms, Ureteral Neoplasms, Neoplasms, Neoplasm Metastasis, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    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)

  • GemcitabineDrug

    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

  • ALT-801Biological

    Also called c264scTCR-IL2

    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

Study groups in NCT01326871
Study groupRoleWhat they receive
ALT-801 0.04 mg/kg with Cisplatin and GemcitabineExperimentalNot described
Receives: Drug: Cisplatin; Drug: Gemcitabine; Biological: ALT-801
ALT-801 0.06 mg/kg with Cisplatin and GemcitabineExperimentalNot described
Receives: Drug: Cisplatin; Drug: Gemcitabine; Biological: ALT-801
ALT-801 0.06 mg/kg with GemcitabineExperimentalNot described
Receives: Drug: Gemcitabine; Biological: ALT-801

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 8 weeks

  2. Number of Participants With Adverse Events

    Number of AEs that occur or worsen after the first dose of study treatment

    Measured: 8 weeks

  3. Objective Response Rate in Treated Patients

    Objective response rate (ORR) is defined as confirmed complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors [RECIST V1.0]: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2011 (estimated)
  2. Study start6 Sep 2011
  3. Primary completion11 Apr 2016
  4. Study completion11 Apr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01326871
Sponsor's protocol ID
CA-ALT-801-01-10
Status last verified
Jun 2024
First submitted
30 Mar 2011
Last updated
25 Jun 2024
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cisplatin, Gemcitabine and ALT-801 in people with Transitional Cell Carcinoma of Bladder and Urethra Cancer, run by Altor BioScience at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01326871.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.

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