Uterine Cervical NeoplasmsPhase 1CC-OV01NCT05393440

First-in-human (FIH) Phase I Trial of BS-006 in Cervical Cancer

A Phase 1 study testing BS-006 in people with Uterine Cervical Neoplasms, run by Zhongnan Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Trial summary

This is a two-stage phase I clinical trial with oncolytic viruses BS-006 in recurrent or metastasis cervical cancer patients who failed in second line treatment. Read more about this study

Who is it for?: Ages 18 to 75 years, women only
Conditions the study is for: Uterine Cervical Neoplasms
What is being tested?: BS-006
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteChina
Study dates: 16 Sep 2022to 1 Jul 2024
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 18 to 75 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Older than 18 years old and younger than 75 years old;
Zubrod-ECOG-WHO performance status is 0-1;
Life expectancy is longer than 3 months;
Pathologically proven malignant tumor originating from cervix uterine. All pathological types are acceptable except for sarcoma of any subtypes;
Radiological confirmed progression after at least 2 lines prior treatment or intolerable toxicity events occur during the second or later line treatment: 1) Neoadjuvant or adjuvant chemotherapy for no less than 2 cycles should be regarded as a separate treatment line if disease progress within 6 months after treatment finish;2) Regional treatment such as brachytherapy, radiofrequency ablation and artery embolization therapy should not be considered as a treatment line; 3) Treatment shift due to toxicity without radiological progression should not be counted as a separate line;
At least one measurement lesion according to RECIST 1.1;

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At least one lesion with maximum diameter is larger than 1cm and surgically accessibility;
Patients must have recovered from prior treatment related toxicity to CTCAE grade 1 or 0;
Time interval to last systematic treatment or radiation affecting more than 20% bone marrow must be more than 4 weeks;
Time interval to last major surgery must be more than 4 weeks;
Abundant organ function: 1) Absolute neutrophil count is more than 1500/mm3 without granulocyte colony stimulating factor in the prior 7 days or long-acting granulocyte colony stimulating factor in the prior 20 days; platelets count is more than 100,000/mm3 without thrombopoietic drugs in the prior 7 days or platelet transfusion in the prior 10 days; hemoglobin is more than 9.0g/dL without red blood cell transfusion in the prior 20 days; 2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are lower than 2.5-fold upper limit of normal (ULN); serum bilirubin is lower than 1.5-fold ULN; serum albumin is more than 3g/dL; 3) Serum creatinine is lower than 1.5-fold ULN; 4) Prothrombin time and activated partial thromboplastin time is lower than 1.3-fold ULN;
Patients must have fully recovered from suspected or diagnosed genital herpes beyond 3 months;
Patients or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirement;
Women of childbearing potential must agree to use highly effective contraceptive methods in while on study drug and for at least 3 months after the last injection of BS-006. The pregnancy test within 7 days prior to the first injection must be negative.

Who cannot join

Cervical sarcoma of any subtype or prior history of other malignancy within 5 years;
Central nerve system metastasis;
Lesions met the requirement outlined in the inclusion criteria are unsafe for injection evaluated by investigators;
Severe comorbidities of any organs, including but not limit to myocardial infarction within 6 months, unstable angina pectoris, congestive heart failure, grade 3 or higher hypertension per CTCAE, cardiac arrhythmias, uncontrolled diabetes, fever of unknown reason, active digest ulcer and chronic obstructive pulmonary disease;
History of central nervous system infectious or demyelinating disease;
Severe infectious disease requiring constant antibiotic treatment;

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Systematic glucocorticoids use within 2 weeks or glucocorticoids need for a long term;
Active infection of hepatitis B or C, HIV, cytomegalovirus, syphilis or other virus requiring treatment;
Immune disorder disease;
Antiviral treatment of any kinds;
Prior participant in experimental viral therapy;
Allergy to herpes simplex virus vaccine;
Participation in another research study within 4 weeks;
Poor compliance or incapacitated patients due to mental illness or other reasons;
Pregnancy or lactation.

Trial locations and contacts

1 site in 1 country.

Shaoxing Sun, M. D. contact

+08613871286154

sunshaoxing@whu.edu.cn

China1 site, 1 recruiting

Zhongnan Hospital of Wuhan University
Wuhan, Hubei, 430071
Shaoxing Sun, +8613871286154, sunshaoxing@whu.edu.cn
Hui Qiu, Ph.D.
Recruiting

Other trials in China

About this study

Official title: A First-in-human Phase I Two-stage Clinical Trial for Intratumoral Injection of Recombinant Oncolytic Type II Herpes Simplex Virus (BS-006) in Patients With Recurrent Cervical Cancer

This is a two-stage phase I clinical trial with oncolytic viruses BS-006 in recurrent or metastasis cervical cancer patients who failed in second line treatment.

Read the detailed description

This trial includes accelerated dose-escalation stage and dose-expansion stage. An engineered modification oncolytic viruses, BS-006, derived from type II herpes simplex virus strain are planed to be injected into the tumor every two weeks until disease progression or unacceptable toxicity or withdrawn of consent or no lesion suitable for injection or death. In dose-escalation stage, there are three dose levels (1 million, 10 millions, 100 millions 50 % cell culture infectious dose (CCID50)/ml) . Treatment dose will escalate to next higher level if no dose limiting toxicity happens for one time of injection in 3 subjects. Maximal tolerable dose is defined as the highest dose with no more than one dose limiting toxicity and is recommended for dose expansion stage. In dose-expansion stage, 15 subjects will be enrolled. BS-006 viruses will be injected into proper tumor lesions every 2 weeks until disease progression or unacceptable toxicity or withdrawn of consent or no lesion suitable for injection or death. Radiology assessment will repeat every 6 weeks. Dose interruption, not reduction, is permitted in this stage.

Conditions: Uterine Cervical Neoplasms
Being tested: BS-006
Keywords: Uterine Cervical Neoplasms, Oncolytic viruses, BS-006, Phase I clinical trial, Investigator initiated trial
Medical subject headings: Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BS-006Biological
Also called Recombinant oncolytic type II herpes simplex virus
BS-006 is an engineered recombinant type II herpes simplex virus (HSV2) designed and produced by Wuhan Binhui Biopharmaceutical Co., Ltd. It was derived from HSV2 strain HG52. ICP34.5 and ICP47 genes were deleted to ensure abortive infection and immune destruction in normal cells. Bispecific T cell engager of anti-CD3 antibody and anti-PD-L1 antibody were constructed and inserted into HG52 strain genome.

Study groups in NCT05393440
Study group	Role	What they receive
Dose-escalation cohort	Experimental	Three subjects will be enrolled in this cohort. First subject will receive first injection in dose level of 1 million CCID50/mL. If tolerated, second injection for this subject will be accelerated to 10 millions CCID50/mL. If tolerated, the third injection will be further accelerated to 100 million CCID50/mL. The maximum volume for per injection time point is 8 mL. Injection will repeat every two weeks until disease progression or unacceptable toxicity or withdrawn of consent or no lesion suitable for injection or death. If dose limiting toxicity (DLT) happens in any dose level, the injection dose will be decrease to the last tolerable level. Receives: Biological: BS-006
Dose-expansion cohort	Experimental	Fifteen subjects will be enrolled in this cohort. The maximal tolerable dose (MTD) confirmed in the first stage will be utilized in 15 patients. This stage should not be initiated before the completion of dose escalation of all three subjects in the first stage. Treatment will be repeated every two weeks until disease progression or unacceptable toxicity or withdrawn of consent or no lesion suitable for injection or death. Dose interruption, not reduction, is permitted. Treatment will be terminated if toxicity-related treatment interrupt is longer than 28 days. Radiology assessment will be conducted every six weeks. Receives: Biological: BS-006

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximal tolerable dose
The dose level at which there is no more than one DLT happens in dose-escalation stage
Measured: 2 months after initiation of enrollment
Rate and grade of adverse events
The incidence of adverse events and severity graded according to CTCAE 5.0
Measured: From enrollment to 90 days after last treatment of all subjects
Cope numbers of BS-006
Detection of BS-006 virus copy numbers in urine, stool, saliva, blood and wiper of injection point and perineum
Measured: 1 hours predose and 0.5 hours post-dose for first three doses and 1 hours predose ever after

Secondary outcomes (4)

Tumor response rate
Tumor change assessed by investigator according to RECIST 1.1
Measured: Up to 2 years
Abscopal effect rate
Rate of subjects who showed tumor shrinkage for any untreated lesion
Measured: Up to 2 years
Progression free survival rate
Proportion of participants without tumor recurrence or death
Measured: Up to 2 years
Overall survival rate
Proportion of survival participants
Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Sep 20221 Jul 2024

First posted26 May 2022
Study start16 Sep 2022
Primary completion31 Dec 2023 (estimated)
Study completion1 Jul 2024 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Uterine Cervical NeoplasmsStudies 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: Sequential
Masking: None (open label)
Enrolment: 18 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05393440
Sponsor's protocol ID: CC-OV01
Acronym: CC-OV01
Status last verified: Apr 2023
First submitted: 19 May 2022
Last updated: 7 Apr 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Mondal M, Guo J, He P, Zhou D. Recent advances of oncolytic virus in cancer therapy. Hum Vaccin Immunother. 2020 Oct 2;16(10):2389-2402. doi: 10.1080/21645515.2020.1723363. Epub 2020 Feb 20.
PubMed 32078405
Kohlhapp FJ, Kaufman HL. Molecular Pathways: Mechanism of Action for Talimogene Laherparepvec, a New Oncolytic Virus Immunotherapy. Clin Cancer Res. 2016 Mar 1;22(5):1048-54. doi: 10.1158/1078-0432.CCR-15-2667. Epub 2015 Dec 30.
PubMed 26719429
Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.
PubMed 26014293
Raja J, Ludwig JM, Gettinger SN, Schalper KA, Kim HS. Oncolytic virus immunotherapy: future prospects for oncology. J Immunother Cancer. 2018 Dec 4;6(1):140. doi: 10.1186/s40425-018-0458-z.
PubMed 30514385

Want to know more?

Shaoxing Sun, M. D.

+08613871286154

sunshaoxing@whu.edu.cn

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)
Cervical Cancer
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 4
Ocular Assessments in Patients Treated With Tivdak® in Recurrent or Metastatic Cervical Cancer
Cervical Cancer
Recruiting
Use Misoprostol to Optimize Prevention of Cervical Cancer
Cervical Cancers
RecruitingObservational study
Role of Liquid Biopsies in HPV-associated Cancer Treatment Monitoring
Cervical Cancer, Cervical Dysplasia

All Uterine Cervical Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A First-in-human Phase I Two-stage Clinical Trial for Intratumoral Injection of Recombinant Oncolytic Type II Herpes Simplex Virus (BS-006) in Patients With Recurrent Cervical Cancer
ClinicalTrials.gov ID: NCT05393440
Acronym / sponsor ID: CC-OV01 / CC-OV01
Conditions: Uterine Cervical Neoplasms
Keywords: Uterine Cervical Neoplasms, Oncolytic viruses, BS-006, Phase I clinical trial, Investigator initiated trial
Phase: Phase 1
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 18 participants (estimated)
Lead sponsor: Zhongnan HospitalUniversity, hospital or other
Collaborators: Binhui Biopharmaceutical Co., Ltd.
Study start: 16 Sep 2022 (actual)
Primary completion: 31 Dec 2023 (estimated)
Study completion: 1 Jul 2024 (estimated)
First posted: 26 May 2022 (actual)
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.

This is a two-stage phase I clinical trial with oncolytic viruses BS-006 in recurrent or metastasis cervical cancer patients who failed in second line treatment.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Dose-escalation cohort	Experimental	Biological: BS-006Three subjects will be enrolled in this cohort. First subject will receive first injection in dose level of 1 million CCID50/mL. If tolerated, second injection for this subject will be accelerated to 10 millions CCID50/mL. If tolerated, the third injection will be further accelerated to 100 million CCID50/mL. The maximum volume for per injection time point is 8 mL. Injection will repeat every two weeks until disease progression or unacceptable toxicity or withdrawn of consent or no lesion suitable for injection or death. If dose limiting toxicity (DLT) happens in any dose level, the injection dose will be decrease to the last tolerable level.
Dose-expansion cohort	Experimental	Biological: BS-006Fifteen subjects will be enrolled in this cohort. The maximal tolerable dose (MTD) confirmed in the first stage will be utilized in 15 patients. This stage should not be initiated before the completion of dose escalation of all three subjects in the first stage. Treatment will be repeated every two weeks until disease progression or unacceptable toxicity or withdrawn of consent or no lesion suitable for injection or death. Dose interruption, not reduction, is permitted. Treatment will be terminated if toxicity-related treatment interrupt is longer than 28 days. Radiology assessment will be conducted every six weeks.

Who may qualify

Ages: 18 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Older than 18 years old and younger than 75 years old;
Zubrod-ECOG-WHO performance status is 0-1;
Life expectancy is longer than 3 months;
Pathologically proven malignant tumor originating from cervix uterine. All pathological types are acceptable except for sarcoma of any subtypes;
Radiological confirmed progression after at least 2 lines prior treatment or intolerable toxicity events occur during the second or later line treatment: 1) Neoadjuvant or adjuvant chemotherapy for no less than 2 cycles should be regarded as a separate treatment line if disease progress within 6 months after treatment finish;2) Regional treatment such as brachytherapy, radiofrequency ablation and artery embolization therapy should not be considered as a treatment line; 3) Treatment shift due to toxicity without radiological progression should not be counted as a separate line;

Key exclusion criteria (15 listed)

Cervical sarcoma of any subtype or prior history of other malignancy within 5 years;
Central nerve system metastasis;
Lesions met the requirement outlined in the inclusion criteria are unsafe for injection evaluated by investigators;
Severe comorbidities of any organs, including but not limit to myocardial infarction within 6 months, unstable angina pectoris, congestive heart failure, grade 3 or higher hypertension per CTCAE, cardiac arrhythmias, uncontrolled diabetes, fever of unknown reason, active digest ulcer and chronic obstructive pulmonary disease;
History of central nervous system infectious or demyelinating disease;

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
BS-006Also: Recombinant oncolytic type II herpes simplex virusBS-006 is an engineered recombinant type II herpes simplex virus (HSV2) designed and produced by Wuhan Binhui Biopharmaceutical Co., Ltd. It was derived from HSV2 strain HG52. ICP34.5 and ICP47 genes were deleted to ensure abortive infection and immune destruction in normal cells. Bispecific T cell engager of anti-CD3 antibody and anti-PD-L1 antibody were constructed and inserted into HG52 strain genome.	Biological	Dose-escalation cohort, Dose-expansion cohort

Primary outcome

Maximal tolerable dose
Time frame: 2 months after initiation of enrollment
The dose level at which there is no more than one DLT happens in dose-escalation stage
Rate and grade of adverse events
Time frame: From enrollment to 90 days after last treatment of all subjects
The incidence of adverse events and severity graded according to CTCAE 5.0
Cope numbers of BS-006
Time frame: 1 hours predose and 0.5 hours post-dose for first three doses and 1 hours predose ever after
Detection of BS-006 virus copy numbers in urine, stool, saliva, blood and wiper of injection point and perineum

4 secondary outcomes

Tumor response rate
Time frame: Up to 2 years
Abscopal effect rate
Time frame: Up to 2 years
Progression free survival rate
Time frame: Up to 2 years
Overall survival rate
Time frame: Up to 2 years

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
Background: PubMed 32078405Mondal M, Guo J, He P, Zhou D. Recent advances of oncolytic virus in cancer therapy. Hum Vaccin Immunother. 2020 Oct 2;16(10):2389-2402. doi: 10.1080/21645515.2020.1723363. Epub 2020 Feb 20.
Background: PubMed 26719429Kohlhapp FJ, Kaufman HL. Molecular Pathways: Mechanism of Action for Talimogene Laherparepvec, a New Oncolytic Virus Immunotherapy. Clin Cancer Res. 2016 Mar 1;22(5):1048-54. doi: 10.1158/1078-0432.CCR-15-2667. Epub 2015 Dec 30.
Background: PubMed 26014293Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.
Background: PubMed 30514385Raja J, Ludwig JM, Gettinger SN, Schalper KA, Kim HS. Oncolytic virus immunotherapy: future prospects for oncology. J Immunother Cancer. 2018 Dec 4;6(1):140. doi: 10.1186/s40425-018-0458-z.
Individual participant dataSharing planned: No

Related trials for Uterine Cervical Neoplasms

RecruitingPhase 3
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)
Cervical Cancer
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Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
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Recruiting
Use Misoprostol to Optimize Prevention of Cervical Cancer
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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.

Shaoxing Sun, M. D. contact

+08613871286154

sunshaoxing@whu.edu.cn

Hui Qiu, Ph. D. principal investigator

Wuhan University

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 BS-006 in people with Uterine Cervical Neoplasms, run by Zhongnan Hospital at 1 site in China.

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 14 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 7 Apr 2023. 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 China. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Shaoxing Sun, M. D. (+08613871286154, sunshaoxing@whu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal tolerable dose (time frame: 2 months after initiation of enrollment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05393440, which also lists 4 linked publications.

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 7 Apr 2023.