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Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies (TEMPO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03663712
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : January 10, 2020
Sponsor:
Information provided by (Responsible Party):
Dan Blazer III, M.D., Duke University

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.

Condition or disease Intervention/treatment Phase
Stage IV Peritoneal Surface Dissemination From Gastrointestinal or Recurrent, Platinum-resistant Ovarian Cancer That Cannot be Completely Resected Biological: Talimogene Laherparepvec Phase 1

Detailed Description:

This is a non-randomized, open-label Phase I trial in patients with Stage IV peritoneal surface dissemination from gastrointestinal or recurrent, platinum-resistant ovarian tumors enrolled at Duke Cancer Institute. All subjects will complete an extensive medical history, baseline physical examination and clinical assessment to ensure subject eligibility requirements within 4 weeks of starting study drug. All eligible patients must have a peritoneal catheter placed at least 2 weeks prior to the initiation of therapy. All patients will receive an initial loading dose of TVEC 4x106 Plaque Forming Units (PFU) on Cycle 1 Day 1 to enable the formation of protective antibodies as described in the currently approved treatment protocol for the treatment of cutaneous melanoma. Three weeks after the initial loading dose, patients will receive TVEC at the dose level for the cohort for which they are enrolled every 2 weeks for up to 4 doses. The length of the first cycle is 5 weeks and subsequent cycles are 2 weeks in duration.

The first portion of the study, the Dose Escalation cohort, will evaluate the toxicity profile of TVEC in patients with peritoneal surface dissemination from gastrointestinal or recurrent, platinum-resistant ovarian tumors. Using a standard '3+3' dose escalation design, there are up to three dose levels that may be explored. Dose escalation will be dependent on dose-limiting toxicity (DLT) within the cohorts.

Once the MTD has been determined, an additional 6 subjects will be enrolled to the dose expansion cohort. All subjects will receive an initial loading dose of TVEC 4x106 PFU on Cycle 1 Day 1. Three weeks after the initial loading dose, patients will receive TVEC at the MTD every 2 weeks for up to 4 doses. The length of the first cycle is 5 weeks and the subsequent cycles are 2 weeks in duration. There are a total of four cycles.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies
Actual Study Start Date : May 9, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : March 1, 2022


Arm Intervention/treatment
Experimental: Dose

Drug: Talimogene Laherparepvec

There will be two parts to this phase I study: 1) Dose Escalation Cohort; 2.) Dose Expansion Cohort

In the Dose Escalation Cohort, three subjects will be enrolled at the starting dose of 4x106 PFU, and the dosing will continue in the standard '3+3' dose escalation scheme. If the starting dose is tolerated, enrollment will continue at 4x107 and 4x108 PFU. Once the MTD is determined, six subjects will be enrolled to the Dose Expansion Cohort at the MTD. All subjects will be dosed with talimogene laherparepvec intraperitoneal (IP) once every 2 weeks for up to 4 doses (in addition to the initial seroconversion dose, which all patients will receive).

Biological: Talimogene Laherparepvec
TVEC is an oncolytic, genetically modified virus designed to reproduce in tumor tissue and stimulate your immune system to attack the tumor cells
Other Name: (T-VEC)




Primary Outcome Measures :
  1. Most Tolerable Dose (MTD) for talimogene laherparepvec [ Time Frame: MTD for the study will be determined at the completion of Phase I dose escalation cohort; estimated as 1 year ]
    The MTD across three dose levels will be determined and the safety analyses will be performed on the safety population

  2. Non-dose limiting toxicities for talimogene laherparepvec [ Time Frame: Continuous, approximately every 4 weeks minimum until end of study estimated at 4 years ]
    Adverse events will be recorded



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have stage IV peritoneal surface dissemination of gastrointestinal cancer that cannot be completely resected at the time of abdominal exploration, or recurrent, platinum-resistant ovarian cancer with peritoneal metastasese. Radiographically measurable disease is preferable, but for patients with previously documented gastrointestinal or ovarian cancer, for whom tumor markers (CEA or CA-125) have been useful markers of disease progression and/or response to treatment, a rising tumor marker (CEA or CA-125) could be substituted for radiographic imaging.
  2. 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.
  3. Age ≥ 18 years
  4. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2
  5. Adequate marrow function as evidenced by:

    1. Absolute neutrophil count (ANC) ≥ 2,000/µL
    2. Platelets ≥ 100,000/µL
    3. Hemoglobin (Hgb) ≥ 9 g/dL
  6. 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.
  7. Adequate hepatic function as evidenced by:

    1. Serum bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level > 1.5 x ULN
    2. Aspartate aminotransferase (AST) ≤ 3 x ULN
    3. Alanine aminotransferase (ALT) ≤ 3 x ULN
    4. Alkaline phosphatase ≤ 3 x ULN
  8. INR or PT ≤ 1.5 x ULN, unless the subject is receiving anticoagulant therapy, in which case PT and PTT/aPTT must be within therapeutic range of intended use of anticoagulants (and may need to be held per institutional standards for placement of the Bard peritoneal catheter).
  9. Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy.
  10. Patients of reproductive potential (men and women) must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) at the time of pregnancy test (women of childbearing potential only), during the course of the study and for 90 days after the last dose of study drug, even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of study and for 90 days after the last dose of study drug.
  11. Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial.

Exclusion Criteria:

  1. 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.
  2. Patients who received radiotherapy to more than 25% of their bone marrow.
  3. 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.
  4. 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.
  5. Metastatic disease in a site other than the peritoneal surfaces.
  6. 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.
  7. Evidence of clinically significant immunosuppression such as the following:

    1. Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease.
    2. Concurrent opportunistic infection.
    3. Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses >10mg/day of prednisone or equivalent within 7 days prior to enrollment.
  8. History of allogenic organ or hematopoietic transplant.
  9. 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.
  10. Requiring intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use.
  11. Prior treatment with talimogene laherparepvec or any other oncolytic virus.
  12. Subject has known sensitivity to talimogene laherparepvec or any of its components to be administered during dosing.
  13. Prior therapy with tumor vaccine.
  14. Receipt of a live vaccine within 28 days prior to enrollment.
  15. Known to have acute or chronic active hepatitis B or C infection (active, previously treated, or both).
  16. Known history of HIV infection.
  17. Active infection or fever ≥ 101.3°F within 3 days of the first scheduled day of protocol treatment.
  18. Peripheral neuropathy ≥ Grade 2.
  19. Bleeding disorders that would preclude intraperitoneal port placement.
  20. Refractory ascites that requires palliative paracentesis more frequently than once a month. Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study or interferes with the interpretation of the results.
  21. History of other malignancy within the past 5 years.
  22. Female subjects who are pregnant or breast-feeding, or planning to become pregnant during study treatment or through 90 days after the last dose of talimogene laherparepvec.
  23. Subjects of childbearing potential who are unwilling to use acceptable method(s) of effective contraception during study treatment and through 90 days after the last dose of talimogene laherparepvec.
  24. Sexually active subjects and their partners unwilling to use male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 90 days after treatment with talimogene laherpareapvec.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03663712


Contacts
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Contact: Emily Bolch (919) 668 6359 emily.bolch@duke.edu
Contact: Francisco Cordero, PhD (919) 681-3095 francisco.cordero@duke.edu

Locations
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United States, Illinois
University of Illinois College of Medicine at Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Meredith Russel    312-355-5112    mrussel3@uic.edu   
Principal Investigator: John H Stewart, IV, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Ireka Burrus    919-668-3041    ireka.burrus@duke.edu   
Principal Investigator: Dan Blazer III, MD         
Wake Forest University School of Medicine Recruiting
Winston-Salem, North Carolina, United States, 27013
Sponsors and Collaborators
Dan Blazer III, M.D.
Investigators
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Principal Investigator: Dan Blazer, MD Duke University
Study Chair: John H Stewart, MD University of Illinois College of Medicine at Chicago
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Responsible Party: Dan Blazer III, M.D., Principal Investigator, Duke University
ClinicalTrials.gov Identifier: NCT03663712    
Other Study ID Numbers: Pro00086917
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: January 10, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Peritoneal Neoplasms
Neoplasms
Neoplasms by Site
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Talimogene laherparepvec
Antineoplastic Agents, Immunological
Antineoplastic Agents