RhabdomyosarcomaPhase 1NCT00931931
HSV1716 in Patients With Non-Central Nervous System (Non-CNS) Solid Tumors
A Phase 1 study testing HSV1716 in people with Rhabdomyosarcoma and Osteosarcoma, run by Timothy Cripe at 1 site in United States.
Trial summary
Patients with relapsed solid tumors such as sarcomas and neuroblastoma have a poor survival, generally < 20%. There is an urgent need for new treatments that are safe and effective. Read more about this study
- Who is it for?
- Ages 7 to 30 years
- Conditions the study is for
- Rhabdomyosarcoma, Osteosarcoma, Ewing Sarcoma
- What is being tested?
- HSV1716
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to 19 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 7 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Inclusion of Women and Minorities: The study is open to all participants regardless of gender or ethnicity.
- Inclusion for intratumoral injection: Subject must have 1-3 lesions amenable to HSV1716 administration by needle if superficial; by needle and/or catheter if deep or pulmonary, via interventional radiology without undue risk. Lesion(s) must meet size criteria specified in section 4.4.9.
- Inclusion for intravenous administration: Subject must have metastatic disease or a lesion not deemed suitable for direct injection.
- Age: Subjects must be greater than or equal to 7 years and less than or equal to 30 years of age at the time of signing consent (study entry);
- Histologic Diagnosis: Subjects must have had histologic verification a non-CNS solid tumor at original diagnosis. The tumor must be amenable to HSV1716 administration without undue risk. Disease must be considered refractory to conventional therapy or for which no conventional therapy exists.
- Metastatic Disease: Subjects who have metastasis to the brain are eligible for the intratumoral arm of this study; however, no metastatic sites within the brain will be considered for injection. Subjects who have metastasis to the brain are eligible for the intravenous arm of this study only if those metastases have been treated and are no longer active.
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- Performance Level: Karnofsky greater than or equal to 50. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
- Subjects must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study;
- Myelosuppressive chemotherapy: Must not have received within 28 days of entry onto this study (42 days if prior nitrosourea) accompanied by hematopoietic recovery, or 14 days of stopping non-myelosuppressive therapy as long as hematopoietic requirements are met;
- Biologic (anti-neoplastic agent): Must not have received within 7 days of entry onto this study (21 days if prior VEGF-Trap and at least 3 half-lives after last dose of a monoclonal antibody). For biologic agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur;
- No Radiation Therapy greater than or equal to 14 days for local palliative XRT (small port): greater than or equal to 6 months must have elapsed if prior craniospinal XRT or if greater than or equal to 50% radiation of pelvis; greater than or equal to 42 days must have elapsed if other substantial bone marrow radiation;
- Immunoablative or myeloablative Stem Cell Transplant (SCT): greater than or equal to 6 months must have elapsed from prior autologous transplant. Subjects must not have graft versus host disease post autologous transplant;
- Investigational agent: greater than or equal to 28 days must have elapsed from treatment with a different phase I agent;
- Subjects with seizure disorder may be enrolled if on anticonvulsants and well controlled.
- At the time of enrollment, specified CNS conditions must be less than or equal to Grade II toxicity per CTCAE 3.0 criteria;
- All subjects must have adequate blood counts defined as: peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL, Platelet count greater than or equal to 100,000/uL (may be a post transfusion value), Hemoglobin greater than or equal to 9.0 gm/dL (may be a post transfusion value)
- Adequate renal function defined as:Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) for age or creatinine clearance or radioisotope GFR greater than or equal to 70 ml/min/1.73 m2;
- Adequate liver function defined as: Total bilirubin less than or equal to 2.0 x ULN for age, and SGPT (ALT) less than or equal to 2.5 x ULN for age and albumin greater than or equal to 2g/dL, GGT < 2.5 x ULN
- Adequate cardiac function as defined by: Shortening fraction >25% by echocardiogram or ejection fraction above the institutional lower limit of normal by MUGA, No focal wall motion abnormalities as determined by either of the above studies, EKG without evidence of ischemia or significant arrythmia
- Adequate coagulation as defined by:PT/INR and PTT <1.5 x ULN for age;
- Infectious Disease: Documented evidence of negative tests for the presence of Hepatitis B surface antigen, Hepatitis C antibody, HIV1 and HIV2 antibodies within the three months preceding study entry. Subjects who do not have such evidence must undergo appropriate testing prior to virus administration;
Who cannot join
- Stem cell transplant: No subjects who have received an allogeneic hematopoietic stem cell transplant are eligible;
- Pregnancy or Breast-Feeding: There is no available information regarding human fetal or teratogenic toxicities. Pregnant women are excluded and pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method from the time of study entry to a period of no less than four months post the final HSV1716 injection. For the same period of time, women who participate in this study must agree not to breast feed;
- Consent: Unable or unwilling to give voluntary informed consent / assent;
- Leukemia: Subjects with leukemia are not eligible for study participation;
- Infection or any other severe systemic disease or medical or surgical condition deemed significant by the principal investigator;
- Administration of any unlicensed or investigational agent within 4 weeks of entry to the study;
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- Growth factor(s): No PEG-GCSF within 14 days of virus injection (day 0);
- Anti-HSV antivirals: Subjects whose physicians determine that anti-HSV antiviral therapy (such as acyclovir, ganciclovir, foscarnet, etc.) cannot be safely discontinued from 2 days prior to the injection to 28 days following the injection should not be in the study.
- Subjects who have other conditions which in the opinion of the investigator contra-indicate the receipt of HSV1716 or indicate subject's inability to follow protocol requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
About this study
Official title: A Phase I Dose Escalation Study of Intratumoral or Intravenous Herpes Simplex Virus-1 Mutant HSV1716 in Patients With Refractory Non-Central Nervous System (Non-CNS) Solid Tumors
Patients with relapsed solid tumors such as sarcomas and neuroblastoma have a poor survival, generally < 20%. There is an urgent need for new treatments that are safe and effective.
HSV1716, an oncolytic virus, is a mutant herpes simplex virus (HSV) type I, deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells - a phenotype exploited to selectively kill tumor cells. In previous clinical studies, HSV1716 has been shown to be safe when injected at doses up to 10^5 plaque forming units (pfu) directly into human high-grade glioma and into normal brain adjacent to tumour, following excision of high-grade glioma. In an extension study, HSV1716 has been shown to be safe when injected at a dose of up to 10^6 pfu directly into brain tumours. Replication of HSV1716 in human glioblastoma in situ has been demonstrated. Following a single administration of HSV1716 by direct injection into active recurrent tumor or brain adjacent to tumor, some patients have lived longer than might have been expected. This study seeks to evaluate the safety of a single injection of HSV1716 in the treatment of extracranial solid tumors in adolescents and young adults.
Read more
HSV1716 has also proved safe when given by direct intra-tumoural injection in patients with squamous carcinoma of the head and neck, and in patients with malignant melanoma.
Replication of HSV mutants in human sarcomas and neuroblastoma in cultured cells and human xenograft models has been demonstrated.
This study is designed in two parts. PART 1 of the study specifies a single dose of virus. Participants who experience at least stable disease or relapse following a determination of stable disease, may qualify for subsequent doses in PART 2. PART 2 requires signing of a separate consent.
Funding Source - FDA OOPD
- Conditions
- Rhabdomyosarcoma, Osteosarcoma, Ewing Sarcoma, Soft Tissue Sarcoma, Neuroblastoma, Wilms Tumor
- Being tested
- HSV1716
- Medical subject headings
- Rhabdomyosarcoma, Osteosarcoma, Sarcoma, Ewing, Sarcoma, Neuroblastoma, Wilms Tumor, Neurofibrosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSV1716Biological
| Study group | Role | What they receive |
|---|---|---|
| HSV1716 - Intratumoral route | Experimental | Research participants with localized disease receiving HSV1716 as an intratumoral injection Receives: Biological: HSV1716 |
| HSV1716 - intravenous | Experimental | Research participants with metastatic disease receiving HSV1716 intravenously Receives: Biological: HSV1716 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine whether intratumoral injection or intravenous infusions of HSV1716 is safe in adolescents and young adults with non-CNS solid tumors.
Measured: Dose limiting toxicities will be assessed at 28 days after injection of HSV1716.
Secondary outcomes (1)
To measure antiviral immune response in patients with refractory cancer treated with HSV1716.
Measured: Antiviral immune response will be assessed 28 days after injection. Beginning at 1.5 years post injection assessments will occur every 6 months. Beginning 5 years after the injection, assessments will occur annually until 15 years post injection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2009 (estimated)
- Study startMar 2010
- Primary completion19 Mar 2018
- Study completion19 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RhabdomyosarcomaStudies 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Timothy Cripe
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Timothy Cripe, Nationwide Children's Hospital
- Investigators
- Timothy Cripe, M.D., PhD., Study director, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00931931
- Sponsor's protocol ID
- IRB13-00471
- Other IDs
- #FD-R-0003717
- Status last verified
- Mar 2018
- First submitted
- 28 May 2009
- Last updated
- 21 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of Intratumoral or Intravenous Herpes Simplex Virus-1 Mutant HSV1716 in Patients With Refractory Non-Central Nervous System (Non-CNS) Solid Tumors
- ClinicalTrials.gov ID
- NCT00931931
- Acronym / sponsor ID
- IRB13-00471
- Conditions
- Rhabdomyosarcoma, Osteosarcoma, Ewing Sarcoma, Soft Tissue Sarcoma, Neuroblastoma, Wilms Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Timothy CripeUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- 19 Mar 2018 (actual)
- Study completion
- 19 Mar 2018 (actual)
- First posted
- 2 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with relapsed solid tumors such as sarcomas and neuroblastoma have a poor survival, generally < 20%. There is an urgent need for new treatments that are safe and effective.
HSV1716, an oncolytic virus, is a mutant herpes simplex virus (HSV) type I, deleted in the RL1 gene which encodes the protein ICP34.5, a specific determinant of virulence. Mutants lacking the RL1 gene are capable of replication in actively dividing cells but not in terminally differentiated cells - a phenotype exploited to selectively kill tumor cells. In previous clinical studies, HSV1716 has been shown to be safe when injected at doses up to 10^5 plaque forming units (pfu) directly into human high-grade glioma and into normal brain adjacent to tumour, following excision of high-grade glioma. In an extension study, HSV1716 has been shown to be safe when injected at a dose of up to 10^6 pfu directly into brain tumours. Replication of HSV1716 in human glioblastoma in situ has been demonstrated. Following a single administration of HSV1716 by direct injection into active recurrent tumor or brain adjacent to tumor, some patients have lived longer than might have been expected. This study seeks to evaluate the safety of a single injection of HSV1716 in the treatment of extracranial solid tumors in adolescents and young adults.
HSV1716 has also proved safe when given by direct intra-tumoural injection in patients with squamous carcinoma of the head and neck, and in patients with malignant melanoma.
Replication of HSV mutants in human sarcomas and neuroblastoma in cultured cells and human xenograft models has been demonstrated.
This study is designed in two parts. PART 1 of the study specifies a single dose of virus. Participants who experience at least stable disease or relapse following a determination of stable disease, may qualify for subsequent doses in PART 2. PART 2 requires signing of a separate consent.
Funding Source - FDA OOPD
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HSV1716 - Intratumoral route | Experimental | Biological: HSV1716Research participants with localized disease receiving HSV1716 as an intratumoral injection |
| HSV1716 - intravenous | Experimental | Biological: HSV1716Research participants with metastatic disease receiving HSV1716 intravenously |
Who may qualify
- Ages
- 7 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Inclusion of Women and Minorities: The study is open to all participants regardless of gender or ethnicity.
- Inclusion for intratumoral injection: Subject must have 1-3 lesions amenable to HSV1716 administration by needle if superficial; by needle and/or catheter if deep or pulmonary, via interventional radiology without undue risk. Lesion(s) must meet size criteria specified in section 4.4.9.
- Inclusion for intravenous administration: Subject must have metastatic disease or a lesion not deemed suitable for direct injection.
- Age: Subjects must be greater than or equal to 7 years and less than or equal to 30 years of age at the time of signing consent (study entry);
- Histologic Diagnosis: Subjects must have had histologic verification a non-CNS solid tumor at original diagnosis. The tumor must be amenable to HSV1716 administration without undue risk. Disease must be considered refractory to conventional therapy or for which no conventional therapy exists.
Key exclusion criteria (9 listed)
- Stem cell transplant: No subjects who have received an allogeneic hematopoietic stem cell transplant are eligible;
- Pregnancy or Breast-Feeding: There is no available information regarding human fetal or teratogenic toxicities. Pregnant women are excluded and pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method from the time of study entry to a period of no less than four months post the final HSV1716 injection. For the same period of time, women who participate in this study must agree not to breast feed;
- Consent: Unable or unwilling to give voluntary informed consent / assent;
- Leukemia: Subjects with leukemia are not eligible for study participation;
- Infection or any other severe systemic disease or medical or surgical condition deemed significant by the principal investigator;
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 |
|---|---|---|
| HSV1716 | Biological | HSV1716 - Intratumoral route, HSV1716 - intravenous |
Primary outcome
To determine whether intratumoral injection or intravenous infusions of HSV1716 is safe in adolescents and young adults with non-CNS solid tumors.
Time frame: Dose limiting toxicities will be assessed at 28 days after injection of HSV1716.
1 secondary outcome
To measure antiviral immune response in patients with refractory cancer treated with HSV1716.
Time frame: Antiviral immune response will be assessed 28 days after injection. Beginning at 1.5 years post injection assessments will occur every 6 months. Beginning 5 years after the injection, assessments will occur annually until 15 years post injection.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2018.
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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.
Timothy Cripe, M.D., PhD. study director
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HSV1716 in people with Rhabdomyosarcoma and Osteosarcoma, run by Timothy Cripe at 1 site 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 9 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 21 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine whether intratumoral injection or intravenous infusions of HSV1716 is safe in adolescents and young adults with non-CNS solid tumors. (time frame: Dose limiting toxicities will be assessed at 28 days after injection of HSV1716.). 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 21 Mar 2018.