Talimogene Laherparepvec in Treating Patients With Non-Muscle Invasive Bladder Transitional Cell Carcinoma

NCT03430687 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 15521NCI-2018-0010915-17558
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of talimogene laherparepvec and to see how well it works in treating patients with non-muscle invasive bladder transitional cell carcinoma. Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may attack specific tumor cells and stop them from growing or kill them.

Conditions

Stage 0 Bladder Urothelial Carcinoma AJCC v6 and v7; Stage 0a Bladder Urothelial Carcinoma AJCC v6 and v7; Stage 0is Bladder Urothelial Carcinoma AJCC v6 and v7; Stage I Bladder Urothelial Carcinoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (3)

• Incidence of treatment-related toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (Dose escalation)

  The distribution for the maximum observed grade for each adverse event will be tabulated and reported with 95% confidence interval.

  Up to 2 years

• Pathologic T0 rate (Dose expansion)

  Point estimates and 95% confidence intervals will be obtained for each dose level of talimogene laherparepvec. Will be estimated for the expansion cohort and compared with the null hypothesis rate separately by using one-sample proportion test.

  At 6 months

• Relapse-free survival rate (Dose expansion)

  Point estimates and 95% confidence intervals will be obtained for each dose level of talimogene laherparepvec. Will be estimated for the expansion cohort and compared with the null hypothesis rate separately by using one-sample proportion test.

  From study start until recurrence of disease or death from any cause, assessed at 2 years

Secondary Outcomes (5)

• Change in antigen presenting cell (APC) within bladder tumor tissue by immunohistochemical (IHC) assessment

  Baseline up to 2 years

• Change in circulating immune cells following intravesical talimogene laherparepvec, by flow cytometric assessment

  Baseline up to 2 years

• Change in T cell and other immune cell infiltration within bladder tumor tissue by IHC assessment

  Baseline up to 2 years

• Herpes simplex virus (HSV) status assessed by rate of HSV seroconversion in patients who were previously HSV-seronegative and relationship between HSV status and immunologic infiltration within tumor

  Up to day 43

• Viral replication as measured by viral titers

  Up to 2 years

Other Outcomes (7)

• Antibody responses measured by spotted antigen arrays

  Up to 6 weeks following therapy

• Apoptosis by IHC assessment of cleaved caspase-3

  Up to 2 years

• Change in PD-L1 expression by IHC assessment

  Baseline up to 2 years

Study Arms (1)

Treatment (talimogene laherparepvec)

EXPERIMENTAL

Patients receive talimogene laherparepvec intravesically (10ml of 10\^6 PFU/mL) on days 1, 8, 15, 22, 29, and 36 or days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Talimogene Laherparepvec

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (talimogene laherparepvec)

Talimogene Laherparepvec BIOLOGICAL

Given intravesically

Also known as: ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene, Imlygic, JS1 34.5-hGMCSF 47- pA-, T-VEC

Treatment (talimogene laherparepvec)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically document transitional cell carcinoma with the presence of any of the following stages: carcinoma in situ (CIS), high-grade Ta, or any grade T1, detectable at the time of study accrual; combinations of the aforementioned stages are acceptable; subjects with mixed histology are required to have a dominant transitional cell carcinoma (TCC) pattern
• Failure of prior intravesical treatment(s), one of which must include a course of BCG; failure is defined as evidence of TCC on cystoscopic examination and biopsy or cystoscopic examination and urine cytology at least 6 weeks from completion of last treatment
• Patient is either ineligible for or declines radical cystectomy; the investigator must explain that a delay in cystectomy may increase the patient?s chance of disease progression
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• Ability to understand and willingness to sign written informed consent
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \< 2.5 x institutional upper limit of normal (ULN) and total bilirubin \< 1.5 x institutional ULN
• Absolut neutrophil count (ANC) \> 1500/uL
• Platelets \>= 75,000/uL
• Hemoglobin \> 8 mg/dL without need for hematopoetic growth factor or transfusion support
• Estimated glomerular filtration rate (GFR) \> 30 ml/min
• Serum creatinine less than 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance = or 60 mL/min for subject with creatinine levels more than 1.5 x ULN; (Note: creatinine clearance need not be determined if the baseline serum creatinine is within normal limits; creatinine clearance should be determined per institutional standard)
• Prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT) =\< 1.5 x ULN
• No known history of human immunodeficiency virus (HIV) 1/2, human T-lymphotropic virus (HTLV)-I/II
• No currently active hepatitis B or C
• Males with partners of childbearing potential, must agree for the duration of the treatment with talimogene laherparepvec and continuing for 3 months after the last tumor injection of talimogene laherparepvec to either:

You may not qualify if:

• Any subjects with muscle-invasive TCC (stages T2 - T4) OR any known TCC of the ureter or renal pelvis are not allowed
• Any history of metastatic TCC; subjects with suspected malignant lymphadenopathy in the abdomen or pelvis are not allowed
• Known active central nervous system (CNS) metastases; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids \> 10 mg/day of prednisone or equivalent; the exception does not include carcinomatosus meningitis which is excluded regardless of clinical stability
• Patients whom, in the opinion of the treating urologic oncologist, should undergo cystectomy due to high-risk features
• Intravesical chemo- or biologic therapy within 6 weeks of first treatment
• Prior systemic chemotherapy for transitional cell carcinoma of the bladder; subjects who have received prior intravesical chemotherapy are allowed if completed 28 days prior to cycle 1 day
• Prior radiation therapy for TCC
• History or evidence of active autoimmune disease, requiring systemic steroid therapy within 28 days of study screening or other systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) or anticipated requirement for systemic immunosuppressive medications during the trial
• Patients on inhaled or topical steroids are eligible
• Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the principal investigator
• Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Major surgery (requiring the use of a general anesthetic) within 4 weeks of study enrollment with the exception of transurethral resection of bladder tumor (TURBT)
• Concurrent use of investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to talimogene laherparepvec
• Malignancies other than urothelial cancer (UC) within 5 years prior to cycle 1, day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent and absence of PSA relapse, or ductal carcinoma in situ of the breast treated surgically with curative intent) or incidental prostate cancer

Sponsors & Collaborators

• University of California, San Francisco: lead
• Amgen: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Interventions

talimogene laherparepvec

Study Officials

• Terence Friedlander

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: February 13, 2018
• Study Start: June 1, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2020
• Last Updated: July 28, 2020

Record last verified: 2020-07

Locations

US (1)