A Phase 1/2 interventional study of Cisplatin and Gemcitabine in Transitional Cell Carcinoma of Bladder, Urethra Cancer and Ureter Cancer, sponsored by Altor BioScience. Completed at 16 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-25.
Sponsored by Altor BioScience · Phase 1/2, Interventional, and Treatment
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.
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
716 studies on the registry are indexed under Carcinoma, Transitional Cell; 201 are open to participants now.
This study's enrollment of 68 is above the median of 49 across 549 interventional studies indexed under Carcinoma, Transitional Cell.
Browse Carcinoma, Transitional Cell studies →Altor BioScience is the lead sponsor of 14 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
ENTRY CRITERIA:
DISEASE CHARATERISTICS:
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
PRIOR/CONCURRENT THERAPY:
PATIENT CHARACTERISTICS:
Age
Performance Status
Bone Marrow Reserve
Renal Function
Glomerular Filtration Rate (GFR):
Hepatic Function
Cardiovascular
Pulmonary
Hematologic
Other
Drug: Cisplatin · Drug: Gemcitabine · Biological: ALT-801
Drug: Cisplatin · Drug: Gemcitabine · Biological: ALT-801
Drug: Gemcitabine · Biological: ALT-801
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)
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
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
Also known as: c264scTCR-IL2
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
Number of Participants With Adverse Events
Number of AEs that occur or worsen after the first dose of study treatment
Time frame: 8 weeks
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.
Time frame: 12 weeks
| Milestone | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine |
|---|---|---|---|
| Started | 3 | 49 | 16 |
| Completed | 3 | 21 | 1 |
| Not completed | 0 | 28 | 15 |
| Withdrew: Major surgery | 0 | 1 | 0 |
| Withdrew: Sae and death | 0 | 2 | 0 |
| Withdrew: Physician decision and decreased performance status | 0 | 1 | 0 |
| Withdrew: Disease progression | 0 | 11 | 5 |
| Withdrew: Did not qualify or consent for repeat treatment | 0 | 1 | 0 |
| Withdrew: Subject decision to continue survival follow-up only | 0 | 4 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 |
| Withdrew: Dlt | 0 | 2 | 0 |
| Withdrew: Sae, disease progression and subject decision | 0 | 1 | 0 |
| Withdrew: Death | 0 | 1 | 0 |
| Withdrew: Other | 0 | 3 | 0 |
| Withdrew: Sae and disease progression | 0 | 0 | 1 |
| Withdrew: Sae and physician decision | 0 | 0 | 1 |
| Withdrew: Did not qualify/consent for repeat treatment, subject decision to continue survival follow-up only | 0 | 0 | 1 |
| Withdrew: Did not qualify or consent for repeat treatment and disease progression | 0 | 0 | 1 |
| Withdrew: Physician decision, aes and subject compliance | 0 | 0 | 1 |
| Withdrew: Physician decision | 0 | 0 | 1 |
| Withdrew: Sae | 0 | 0 | 1 |
| Withdrew: Disease progression and death | 0 | 0 | 1 |
| Withdrew: Subject decision | 0 | 0 | 1 |
| mg/kg Recommended Dose | ALT-801: 0.04 mg/kg, 0.06 mg/kg |
|---|---|
| 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 | 0.06 |
Number of AEs that occur or worsen after the first dose of study treatment
| Participants | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine |
|---|---|---|---|
| Number of Participants With Adverse Events | 3 | 49 | 16 |
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.
| percentage of participants | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine |
|---|---|---|---|
| Objective Response Rate in Treated Patients | 100 (29 to 100) | 47 (33 to 62) | 6 (0 to 30) |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | 2/3 (66.7%) | 0/3 (0%) | 3/3 (100%) |
| ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | 42/49 (85.7%) | 20/49 (40.8%) | 49/49 (100%) |
| ALT-801 0.06 mg/kg With Gemcitabine | 16/16 (100%) | 8/16 (50%) | 16/16 (100%) |
| Event | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine |
|---|---|---|---|
| ConstipationGastrointestinal disorders | 0/3 | 1/49 | 1/16 |
| Small intestinal obstructionGastrointestinal disorders | 0/3 | 0/49 | 1/16 |
| PyrexiaGeneral disorders | 0/3 | 2/49 | 1/16 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/3 | 3/49 | 1/16 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 0/3 | 0/49 | 1/16 |
| Upper respiratory tract infectionInfections and infestations | 0/3 | 0/49 | 1/16 |
| Confusional statePsychiatric disorders | 0/3 | 1/49 | 1/16 |
| HypotensionVascular disorders | 0/3 | 0/49 | 1/16 |
| HypersensitivityImmune system disorders | 0/3 | 0/49 | 1/16 |
| SepsisInfections and infestations | 0/3 | 3/49 | 0/16 |
| Event | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine |
|---|---|---|---|
| NauseaGastrointestinal disorders | 3/3 | 39/49 | 8/16 |
| VomitingGastrointestinal disorders | 3/3 | 29/49 | 6/16 |
| Platelet count decreasedInvestigations | 3/3 | 42/49 | 9/16 |
| Neutrophil count decreasedInvestigations | 3/3 | 28/49 | 2/16 |
| PruritusSkin and subcutaneous tissue disorders | 3/3 | 17/49 | 6/16 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 3/3 | 18/49 | 2/16 |
| FatigueGeneral disorders | 2/3 | 36/49 | 5/16 |
| PyrexiaGeneral disorders | 2/3 | 23/49 | 5/16 |
| ConstipationGastrointestinal disorders | 2/3 | 19/49 | 5/16 |
| White blood cell count decreasedInvestigations | 2/3 | 11/49 | 3/16 |
| Age, Continuous(years) | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine | Total |
|---|---|---|---|---|
| Mean | 61 ± 2.1 | 63 ± 7.9 | 65 ± 9.7 | 63 ± 8.2 |
| Sex: Female, Male(Participants) | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine | Total |
|---|---|---|---|---|
| Female | 1 | 8 | 6 | 15 |
| Male | 2 | 41 | 10 | 53 |
| Ethnicity (NIH/OMB)(Participants) | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 1 | 2 |
| Not Hispanic or Latino | 3 | 47 | 15 | 65 |
| Unknown or Not Reported | 0 | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 2 | 3 |
| White | 3 | 46 | 13 | 62 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 2 | 1 | 3 |
| Subjects with Muscle Invasive or Metastatic Urothelial Cancer(Participants) | ALT-801 0.04 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Cisplatin and Gemcitabine | ALT-801 0.06 mg/kg With Gemcitabine | Total |
|---|---|---|---|---|
| Count of participants | 3 | 49 | 16 | 68 |
Documents are hosted by the registry — open the source record to download them.
This study is completed, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Altor BioScience