Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies

NCT03663712 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Pro00086917
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objective of this open-label, Phase I, trial is to evaluate the toxicity profile of intraperitoneal talimogene laherparepvec (TVEC) in patients with peritoneal surface dissemination from gastrointestinal or recurrent, platinum-resistant ovarian tumors. The secondary objectives are to evaluate the pharmacokinetic profile and viral shedding of TVEC by measuring viral load in serum and urine as well as viral load in peritoneal washings.

Conditions

Peritoneal Surface Malignancy

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  Number of participants who experienced a dose limiting toxicity (DLT)

  from start of treatment until 30-day follow-up visit, up to 14 weeks

Study Arms (3)

4 x 10^6 PFU

EXPERIMENTAL

Dose level 1. Subjects were assigned to receive 4 x 10\^6 PFU of talimogene laherparepvec.

Biological: Talimogene Laherparepvec

4 x 10^7 PFU

EXPERIMENTAL

Dose level 2. Subjects were assigned to receive 4 x 10\^7 PFU of talimogene laherparepvec.

Biological: Talimogene Laherparepvec

4 x 10^8 PFU

EXPERIMENTAL

Dose level 3. Subjects were assigned to receive 4 x 10\^8 PFU of talimogene laherparepvec.

Biological: Talimogene Laherparepvec

Interventions

Talimogene Laherparepvec BIOLOGICAL

TVEC is an oncolytic, genetically modified virus designed to reproduce in tumor tissue and stimulate your immune system to attack the tumor cells

Also known as: (T-VEC)

4 x 10^6 PFU; 4 x 10^7 PFU; 4 x 10^8 PFU

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have stage IV peritoneal surface dissemination of gastrointestinal cancer or recurrent ovarian, fallopian tube or primary peritoneal cancer with metastatic disease to the peritoneum that cannot be completely resected at time of abdominal exploration. Please note:
• Locoregional extension of peritoneal disease beyond the peritoneal cavity (including but not limited to the pleura and subcutaneous soft tissue) is permitted with PI approval,
• Radiographically measurable disease is preferable, but for patients with previously documented gastrointestinal, fallopian tube, ovarian, or primary peritoneal cancer, for whom relevant tumor markers (including but not limited to CEA, CA 19-9 or CA-125) have been useful markers of disease progression and/or response to treatment, an elevated relevant tumor marker (including but not limited to CEA, CA 19-9 or CA-125) above the institutional upper limit of normal could be substituted for radiographic imaging,
• Asymptomatic primary tumors are permitted.
• Subjects must have had at least one prior round of systemic therapy or have refused or be ineligible for standard systemic therapy for their disease type. No prior systemic therapy is required for low grade mucinous cancers.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2
• Adequate marrow function as evidenced by:
• Absolute neutrophil count (ANC) ≥ 2,000/µL
• Platelets ≥ 100,000/µL
• Hemoglobin (Hgb) ≥ 9 g/dL
• Adequate renal function as evidenced by serum creatinine ≤ 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance ≥ 60 mL/min for subject with creatinine levels \> 1.5 x ULN.
• Adequate hepatic function as evidenced by:
• Serum bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level \> 1.5 x ULN
• Aspartate aminotransferase (AST) ≤ 3 x ULN

You may not qualify if:

• Prior chemotherapy, radiotherapy, biological cancer therapy, targeted therapy, or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
• Patients who received radiotherapy to more than 25% of their bone marrow.
• Currently receiving treatment with another investigational device or drug study, or \< 30 days since ending treatment with another investigational device or drug study(s). Other investigational procedures while participating in this study are excluded.
• 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 carcinomatous meningitis, which is excluded regardless of clinical stability.
• Metastatic disease in a site other than the peritoneal surfaces. Note: Locoregional extension of peritoneal disease may be permitted with PI approval.
• History or evidence of active autoimmune disease that requires systemic treatment (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Evidence of clinically significant immunosuppression such as the following:
• Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease.
• Concurrent opportunistic infection.
• Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \>10mg/day of prednisone or equivalent within 7 days prior to enrollment.
• History of allogenic organ or hematopoietic transplant.
• Active herpes simplex virus (HSV) that requires intermittent or chronic systemic anti-herpetic therapy or prior complications of herpetic infection, e.g. herpetic keratitis or encephalitis.
• Requiring intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use.
• Prior treatment with talimogene laherparepvec or any other oncolytic virus.
• Subject has known sensitivity to talimogene laherparepvec or any of its components to be administered during dosing.

Sponsors & Collaborators

• Dan Blazer III, M.D.: lead

Study Sites (3)

University of Illinois College of Medicine at Chicago

Chicago, Illinois, 60612, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27013, United States

Location

MeSH Terms

Conditions

Peritoneal Neoplasms

Interventions

talimogene laherparepvec

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Results Point of Contact

• Title: Dan G. Blazer III, MD
• Organization: Duke University

trey.blazer@duke.edu

919-668-1861

Study Officials

• Dan Blazer, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• John H Stewart, MD

  University of Illinois College of Medicine at Chicago

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 10, 2018
• Study Start: May 23, 2019
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: November 20, 2024
• Results First Posted: November 20, 2024

Record last verified: 2024-09

Locations

US (3)