Peritoneal Surface MalignancyPhase 1TEMPONCT03663712
Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies
A Phase 1 study testing Talimogene Laherparepvec in people with Peritoneal Surface Malignancy, run by Dan Blazer III, M.D. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Peritoneal Surface Malignancy
- What is being tested?
- Talimogene Laherparepvec
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 May 2019to 13 Oct 2022
- Phase
- Phase 1
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Alanine aminotransferase (ALT) ≤ 3 x ULN
- Alkaline phosphatase ≤ 3 x ULN
- 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).
- Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy.
- 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.
- Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial.
Who cannot join
- 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.
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- 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.
- Prior therapy with tumor vaccine.
- Receipt of a live vaccine within 28 days prior to enrollment.
- Known to have acute or chronic active hepatitis B or C infection (active, previously treated, or both).
- Known history of HIV infection.
- Active infection or fever ≥ 101.3°F within 3 days of the first scheduled day of protocol treatment.
- Peripheral neuropathy ≥ Grade 2.
- Bleeding disorders that would preclude intraperitoneal port placement.
- 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.
- History of other malignancy within the past 5 years.
- 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.
- 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.
- 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 laherparepvec.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Illinois College of Medicine at Chicago
Chicago, Illinois, 60612
Duke University Medical Center
Durham, North Carolina, 27710
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27013
About this study
Official title: A Phase I Trial of Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies
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.
Read the 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 4x10^6 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 maximum tolerated dose (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 4x10^6 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.
- Conditions
- Peritoneal Surface Malignancy
- Being tested
- Talimogene Laherparepvec
- Medical subject headings
- Peritoneal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talimogene LaherparepvecBiological
Also called (T-VEC)
TVEC is an oncolytic, genetically modified virus designed to reproduce in tumor tissue and stimulate your immune system to attack the tumor cells
| Study group | Role | What they receive |
|---|---|---|
| 4 x 10^6 PFU | Experimental | Dose level 1. Subjects were assigned to receive 4 x 10^6 PFU of talimogene laherparepvec. Receives: 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. Receives: 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. Receives: Biological: Talimogene Laherparepvec |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
Number of participants who experienced a dose limiting toxicity (DLT)
Measured: from start of treatment until 30-day follow-up visit, up to 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2018
- Study start23 May 2019
- Primary completion13 Oct 2022
- Study completion13 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Peritoneal Surface MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dan Blazer III, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dan Blazer III, M.D., Duke University
- Investigators
- Dan Blazer, MD, Principal investigator, Duke UniversityJohn H Stewart, MD, Study chair, University of Illinois College of Medicine at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03663712
- Sponsor's protocol ID
- Pro00086917
- Acronym
- TEMPO
- Status last verified
- Sep 2024
- First submitted
- 6 Sep 2018
- Last updated
- 20 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Talimogene Laherparepvec for the Treatment of Peritoneal Surface Malignancies
- ClinicalTrials.gov ID
- NCT03663712
- Acronym / sponsor ID
- TEMPO / Pro00086917
- Conditions
- Peritoneal Surface Malignancy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Dan Blazer III, M.D.University, hospital or other
- Study start
- 23 May 2019 (actual)
- Primary completion
- 13 Oct 2022 (actual)
- Study completion
- 13 Oct 2022 (actual)
- First posted
- 10 Sep 2018 (actual)
- Results
- Posted 20 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 4x10^6 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 maximum tolerated dose (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 4x10^6 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 4 x 10^6 PFU | Experimental | Biological: Talimogene LaherparepvecDose level 1. Subjects were assigned to receive 4 x 10^6 PFU of talimogene laherparepvec. |
| 4 x 10^7 PFU | Experimental | Biological: Talimogene LaherparepvecDose level 2. Subjects were assigned to receive 4 x 10^7 PFU of talimogene laherparepvec. |
| 4 x 10^8 PFU | Experimental | Biological: Talimogene LaherparepvecDose level 3. Subjects were assigned to receive 4 x 10^8 PFU of talimogene laherparepvec. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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:
- 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:
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Talimogene LaherparepvecAlso: (T-VEC)TVEC is an oncolytic, genetically modified virus designed to reproduce in tumor tissue and stimulate your immune system to attack the tumor cells | Biological | 4 x 10^6 PFU, 4 x 10^7 PFU, 4 x 10^8 PFU |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: from start of treatment until 30-day follow-up visit, up to 14 weeks
Number of participants who experienced a dose limiting toxicity (DLT)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dan Blazer, MD principal investigator
Duke University
John H Stewart, MD study chair
University of Illinois College of Medicine at Chicago
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Talimogene Laherparepvec in people with Peritoneal Surface Malignancy, run by Dan Blazer III, M.D. at 3 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?
The sponsor lists 21 inclusion and 27 exclusion criteria. 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 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 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.
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 20 Nov 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?
Dose Limiting Toxicity (DLT) (time frame: from start of treatment until 30-day follow-up visit, up to 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Nov 2024.