Ovarian CancerPhase 1OLIVIANCT04163094
Ovarian Cancer Treatment With a Liposome Formulated mRNA Vaccine in Combination With (Neo-)Adjuvant Chemotherapy
A Phase 1 study testing W_ova1 Vaccine in people with Ovarian Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
This is a first-in-human, open label phase I study in ovarian cancer patients with primary disease eligible for standard-of-care treatment with neo-adjuvant chemotherapy, i.e. 3 cycles carboplatin/paclitaxel, interval surgery and 3 additional cycles carboplatin/paclitaxel. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- W_ova1 Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteNetherlands
- Study dates
- 25 Nov 2019to 26 Jun 2023
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Primary epithelial OC patients with measurable tumor lesions (determined by CT or MRI), who are intended to be treated with neo-adjuvant chemotherapy (carboplatin/paclitaxel), subsequent surgery and adjuvant chemotherapy
- Age ≥ 18 years
- Signed informed consent in accordance with institutional and regulatory guidelines
- Adequate access of the tumor for image-guided biopsy
- Adequate (according to the institutional standards) hematology, liver and kidney function to undergo chemotherapy with carboplatin and paclitaxel
- ECOG-performance status of 0 or 1 at screening
- Current BMI > 18.5 and no weight loss of >5% over the past month. Notably, weight loss due to drainage of ascites is not applicable.
Who cannot join
- History of a second malignancy except for curatively treated low-stage tumors with a histology that can be differentiated from the epithelial OC type
- History of an autoimmune disease, specifically HAV, HBV, HCV and HIV, or any other systemic intercurrent disease or condition that might affect the immunocompetence of the patient, or treatment with systemic highly immunosuppressive therapy (e.g. transplant recipients or patients who underwent a splenectomy)
- Use of systemic continuous corticosteroid therapy (e.g. prednisone i.v. or p.o. >7.5 mg / day).
- Pregnancy or breast feeding
- Participation in a trial with another investigational drug within 30 days prior to the enrolment in this trial
- Any condition that in the opinion of the investigator could interfere with the conduct of the trial.
Trial locations and contacts
1 site in 1 country.
About this study
This is a first-in-human, open label phase I study in ovarian cancer patients with primary disease eligible for standard-of-care treatment with neo-adjuvant chemotherapy, i.e. 3 cycles carboplatin/paclitaxel, interval surgery and 3 additional cycles carboplatin/paclitaxel. Eight doses of the W_ova1 vaccine will be administered prior and in combination with the (neo-)adjuvant chemotherapy to induce an anti-tumor immune response. Systemic immune responses are determined using peripheral blood mononuclear cells collected before, during and after vaccinations. Intratumoral accumulation of T-cells recognizing vaccine-encoded TAAs will be determined before vaccination in a tumor biopsy and after the 3 cycles of chemotherapy and the 5th vaccination using tumor tissue derived from interval surgery. [18F]FB-IL2 PET-CT will be used for the non-invasive assessment of T-cell activation and correlated to immunohistochemistry tumor tissue data from pre-treatment biopsy and interval debulking surgery
Read the detailed description
This is a first-in-human, open label phase I intra-patient dose escalation study (vaccination 1 and 2) in OC patients with primary disease eligible for SoC treatment with neo-adjuvant chemotherapy, i.e. 3 cycles carboplatin/paclitaxel, interval surgery and 3 additional cycles carboplatin/paclitaxel.
OC patients will be vaccinated prior and during (neo)-adjuvant chemotherapy with the W_ova1 vaccine, which includes 3 OC TAA RNAs. Vaccines will be administered by means of intravenous injection. A total of eight vaccinations will be administered with intra-patient dose escalation planned for the first two doses, i.e. the first vaccine will contain 50 µg total RNA and the subsequent seven vaccines will contain the target dose of 100 µg total RNA. Dose reductions/modifications to 50, 25 and 14.4 µg are allowed per protocol.
The first two vaccinations will be administered before the start of neo-adjuvant chemotherapy with 7 day time lag (+/- 2 days) between each vaccination. The subsequent 6 vaccinations are scheduled 15 days (+/- 3 days) after the start of each cycle of chemotherapy to avoid overlap with immune-suppressive corticosteroid premedication as well as with the direct effects of the chemotherapy. Patient evaluation will be performed before, during and after vaccination, including history, physical examination, ECOG performance status and toxicity scoring using NCI CTCAE 5.0 toxicity grades. Blood sample collection for bio monitoring by means of a vena puncture will occur before each vaccination. During the two-step dose escalation blood samples will also be collected 6 hours and 24 hours after vaccination. Blood samples will be analyzed for biochemistry, hematology and tumor marker CA-125.
To determine the systemic immune response (primary objective), PBMCs are obtained by venous blood collection at baseline (100 mL) and twice during study related treatment period (60 mL). In addition, three leukaphereses (or 100 mL blood draw alternatively) and four blood draws for ctDNA analysis are scheduled during the trial for each patient.
To determine the intratumoral immune response (secondary objective), tumor material will be collected before vaccination by an image-guided biopsy and during surgery (standard treatment).
The first [18F]FB-IL2 PET-CT (exploratory objective) will occur at baseline and the second [18F]FB-IL2 PET-CT as close to the surgery as possible. These study procedures are optional and patients can still participate in the trial without the [18F]FB-IL2 PET-CT.
In case of premature drop-out, patients will be asked to undergo the leukapheresis (or 100 mL blood draw alternatively) and if possible / feasible, additional tumor material sampling at time of the planned interval surgery.
- Conditions
- Ovarian Cancer
- Being tested
- W_ova1 Vaccine
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
W_ova1 VaccineDrug
Patients will be treated with a W_ova1 vaccine that includes 3 OC TAA RNA-LPX products.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Patients will receive 8 W_ova1 vaccinations before and during neoadjuvant chemotherapy and adjuvant chemotherapy. Receives: Drug: W_ova1 Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline W_ova1 vaccine antigen-specific T cells in the peripheral blood (systemic induction / expansion of W_ova1 vaccine antigen-specific T cells).
Number of patients with de novo or increased systemic immune responses (based on the ELISpot Data Analysis Tool 1.0) in the post-vaccination PBMC sample compared to baseline PBMC sample to at least one of the three vaccine antigens
Measured: A PBMC collection is planned at baseline, before start treatment. A further PBMC collection is scheduled after 5 vaccinations before surgery. The post-vaccination PBMC collections are scheduled at approx. 14 days and 2.5 months after final vaccination.
Secondary outcomes (3)
Change from baseline W_ova1 vaccine antigen-specific T cells in the tumor (Intratumoral induction / expansion of W_ova1 vaccine antigen-specific T cells)
Number of patients with a significant increase (p<0.05) in CD8-cell density (CD8-cells / mm2 cancer epithelium [cytokeratin-positive area]) in tumor (pre- and post-treatment biopsy)
Measured: Tumor material is collected at baseline by biopsy and compared to tumor material collected during standard-of-care cytoreductive surgery (mid-vaccination, week 12)
Progression free survival
PFS defined as the number of patients alive without any progress or recurrence (local or regional, or distant) and death due to any cause
Measured: Up to 2 years from disease diagnosis
Safety and tolerability of repetitive doses of the W_ova1 vaccine in combination with carboplatin/paclitaxel
Number of patients with AEs, and SAEs
Measured: Up to 28 days after last vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2019
- Study start25 Nov 2019
- Primary completion26 Jun 2023
- Study completion26 Jun 2023
Why it stopped: Despite the extension of the original recruitment period, the target number of evaluable patients defined in the study protocol could not be reached and recruitment for the trial was stopped at that point of time.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- This is a first-in-human, open label phase I study.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- BioNTech SE
- Responsible party
- Principal investigator, Hans W. Nijman, MD PHD, University Medical Center Groningen
- Investigators
- H. W. Nijman, MD/PhD, Principal investigator, University Medical Center Groningen, UMCG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04163094
- Sponsor's protocol ID
- OLIVIA-UMCG-01
- Other IDs
- 2017-004585-10, 2017
- Acronym
- OLIVIA
- Status last verified
- Jun 2023
- First submitted
- 6 Nov 2019
- Last updated
- 29 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovarian Cancer Treatment With a Liposome Formulated mRNA Vaccine in Combination With (Neo-)Adjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT04163094
- Acronym / sponsor ID
- OLIVIA / OLIVIA-UMCG-01
- Conditions
- Ovarian Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Despite the extension of the original recruitment period, the target number of evaluable patients defined in the study protocol could not be reached and recruitment for the trial was stopped at that point of time.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- BioNTech SE
- Study start
- 25 Nov 2019 (actual)
- Primary completion
- 26 Jun 2023 (actual)
- Study completion
- 26 Jun 2023 (actual)
- First posted
- 14 Nov 2019 (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 first-in-human, open label phase I study in ovarian cancer patients with primary disease eligible for standard-of-care treatment with neo-adjuvant chemotherapy, i.e. 3 cycles carboplatin/paclitaxel, interval surgery and 3 additional cycles carboplatin/paclitaxel. Eight doses of the W_ova1 vaccine will be administered prior and in combination with the (neo-)adjuvant chemotherapy to induce an anti-tumor immune response. Systemic immune responses are determined using peripheral blood mononuclear cells collected before, during and after vaccinations. Intratumoral accumulation of T-cells recognizing vaccine-encoded TAAs will be determined before vaccination in a tumor biopsy and after the 3 cycles of chemotherapy and the 5th vaccination using tumor tissue derived from interval surgery. [18F]FB-IL2 PET-CT will be used for the non-invasive assessment of T-cell activation and correlated to immunohistochemistry tumor tissue data from pre-treatment biopsy and interval debulking surgery
Detailed description
This is a first-in-human, open label phase I intra-patient dose escalation study (vaccination 1 and 2) in OC patients with primary disease eligible for SoC treatment with neo-adjuvant chemotherapy, i.e. 3 cycles carboplatin/paclitaxel, interval surgery and 3 additional cycles carboplatin/paclitaxel.
OC patients will be vaccinated prior and during (neo)-adjuvant chemotherapy with the W_ova1 vaccine, which includes 3 OC TAA RNAs. Vaccines will be administered by means of intravenous injection. A total of eight vaccinations will be administered with intra-patient dose escalation planned for the first two doses, i.e. the first vaccine will contain 50 µg total RNA and the subsequent seven vaccines will contain the target dose of 100 µg total RNA. Dose reductions/modifications to 50, 25 and 14.4 µg are allowed per protocol.
The first two vaccinations will be administered before the start of neo-adjuvant chemotherapy with 7 day time lag (+/- 2 days) between each vaccination. The subsequent 6 vaccinations are scheduled 15 days (+/- 3 days) after the start of each cycle of chemotherapy to avoid overlap with immune-suppressive corticosteroid premedication as well as with the direct effects of the chemotherapy. Patient evaluation will be performed before, during and after vaccination, including history, physical examination, ECOG performance status and toxicity scoring using NCI CTCAE 5.0 toxicity grades. Blood sample collection for bio monitoring by means of a vena puncture will occur before each vaccination. During the two-step dose escalation blood samples will also be collected 6 hours and 24 hours after vaccination. Blood samples will be analyzed for biochemistry, hematology and tumor marker CA-125.
To determine the systemic immune response (primary objective), PBMCs are obtained by venous blood collection at baseline (100 mL) and twice during study related treatment period (60 mL). In addition, three leukaphereses (or 100 mL blood draw alternatively) and four blood draws for ctDNA analysis are scheduled during the trial for each patient.
To determine the intratumoral immune response (secondary objective), tumor material will be collected before vaccination by an image-guided biopsy and during surgery (standard treatment).
The first [18F]FB-IL2 PET-CT (exploratory objective) will occur at baseline and the second [18F]FB-IL2 PET-CT as close to the surgery as possible. These study procedures are optional and patients can still participate in the trial without the [18F]FB-IL2 PET-CT.
In case of premature drop-out, patients will be asked to undergo the leukapheresis (or 100 mL blood draw alternatively) and if possible / feasible, additional tumor material sampling at time of the planned interval surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a first-in-human, open label phase I study.
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: W_ova1 VaccinePatients will receive 8 W_ova1 vaccinations before and during neoadjuvant chemotherapy and adjuvant chemotherapy. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Primary epithelial OC patients with measurable tumor lesions (determined by CT or MRI), who are intended to be treated with neo-adjuvant chemotherapy (carboplatin/paclitaxel), subsequent surgery and adjuvant chemotherapy
- Age ≥ 18 years
- Signed informed consent in accordance with institutional and regulatory guidelines
- Adequate access of the tumor for image-guided biopsy
- Adequate (according to the institutional standards) hematology, liver and kidney function to undergo chemotherapy with carboplatin and paclitaxel
Key exclusion criteria (6 listed)
- History of a second malignancy except for curatively treated low-stage tumors with a histology that can be differentiated from the epithelial OC type
- History of an autoimmune disease, specifically HAV, HBV, HCV and HIV, or any other systemic intercurrent disease or condition that might affect the immunocompetence of the patient, or treatment with systemic highly immunosuppressive therapy (e.g. transplant recipients or patients who underwent a splenectomy)
- Use of systemic continuous corticosteroid therapy (e.g. prednisone i.v. or p.o. >7.5 mg / day).
- Pregnancy or breast feeding
- Participation in a trial with another investigational drug within 30 days prior to the enrolment in this trial
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 |
|---|---|---|
| W_ova1 VaccinePatients will be treated with a W_ova1 vaccine that includes 3 OC TAA RNA-LPX products. | Drug | Treatment arm |
Primary outcome
Change from baseline W_ova1 vaccine antigen-specific T cells in the peripheral blood (systemic induction / expansion of W_ova1 vaccine antigen-specific T cells).
Time frame: A PBMC collection is planned at baseline, before start treatment. A further PBMC collection is scheduled after 5 vaccinations before surgery. The post-vaccination PBMC collections are scheduled at approx. 14 days and 2.5 months after final vaccination.
Number of patients with de novo or increased systemic immune responses (based on the ELISpot Data Analysis Tool 1.0) in the post-vaccination PBMC sample compared to baseline PBMC sample to at least one of the three vaccine antigens
3 secondary outcomes
Change from baseline W_ova1 vaccine antigen-specific T cells in the tumor (Intratumoral induction / expansion of W_ova1 vaccine antigen-specific T cells)
Time frame: Tumor material is collected at baseline by biopsy and compared to tumor material collected during standard-of-care cytoreductive surgery (mid-vaccination, week 12)
Progression free survival
Time frame: Up to 2 years from disease diagnosis
Safety and tolerability of repetitive doses of the W_ova1 vaccine in combination with carboplatin/paclitaxel
Time frame: Up to 28 days after last vaccination
Results and safety
The study was stopped early (reason given: Despite the extension of the original recruitment period, the target number of evaluable patients defined in the study protocol could not be reached and recruitment for the trial was stopped at that point of time.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2023.
- Individual participant dataSharing planned: No
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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.
H. W. Nijman, MD/PhD principal investigator
University Medical Center Groningen, UMCG
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 W_ova1 Vaccine in people with Ovarian Cancer, run by University Medical Center Groningen at 1 site in Netherlands.
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 7 inclusion and 6 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: stopped early, as of the sponsor's last update on 29 Jun 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 Netherlands. 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 was stopped early (reason given: Despite the extension of the original recruitment period, the target number of evaluable patients defined in the study protocol could not be reached and recruitment for the trial was stopped at that point of time.). Results are not available in the source record.
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?
Change from baseline W_ova1 vaccine antigen-specific T cells in the peripheral blood (systemic induction / expansion of W_ova1 vaccine antigen-specific T cells). (time frame: A PBMC collection is planned at baseline, before start treatment. A further PBMC collection is scheduled after 5 vaccinations before surgery. The post-vaccination PBMC collections are scheduled at approx. 14 days and 2.5 months after final vaccination.). 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 29 Jun 2023.