Ignite Creation Date:
2024-05-06 @ 1:56 PM
Last Modification Date:
2024-10-26 @ 1:22 PM
Study NCT ID:
NCT04163094
Status:
TERMINATED
Last Update Posted:
2023-06-29
First Post:
2019-11-06
Brief Title:
Ovarian Cancer Treatment With a Liposome Formulated mRNA Vaccine in Combination With Neo-Adjuvant Chemotherapy
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
Official Title:
Ovarian Cancer Treatment With a Liposome Formulated mRNA Vaccine in Combination With Neo-Adjuvant Chemotherapy
Status:
TERMINATED
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
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
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OLIVIA
Brief 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 ie 3 cycles carboplatinpaclitaxel interval surgery and 3 additional cycles carboplatinpaclitaxel 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 18FFB-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 ie 3 cycles carboplatinpaclitaxel interval surgery and 3 additional cycles carboplatinpaclitaxel
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 ie 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 reductionsmodifications to 50 25 and 144 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 50 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 18FFB-IL2 PET-CT exploratory objective will occur at baseline and the second 18FFB-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 18FFB-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
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 ie 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 reductionsmodifications to 50 25 and 144 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 50 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 18FFB-IL2 PET-CT exploratory objective will occur at baseline and the second 18FFB-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 18FFB-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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2017-004585-10 | EUDRACT_NUMBER | None | None |