Advanced Renal Cell CarcinomaPhase 1NCT05641545
IVAC-RCC-001: A Personalized Neoantigen Vaccine as Add-on to Standard of Care Checkpoint Inhibitor in Advanced/Metastatic RCC Patients
A Phase 1 study testing IVAC in people with Advanced Renal Cell Carcinoma, run by SLK Kliniken Heilbronn GmbH at 1 site in Germany.
Trial summary
This is a monocenter, single-arm, prospective phase Ib trial, designed to evaluate the safety, clinical toxicity and in vivo immunological effects of a patient-individualized peptide vaccination added to standard of care checkpoint blockade (nivolumab) in adult patients with metastatic/advanced renal cell carcinoma… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Renal Cell Carcinoma
- What is being tested?
- IVAC
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteGermany
- Study dates
- 17 Oct 2022to 15 Sep 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or older
- Ability to understand and willingness to sign a written informed consent document.
- Patients with RCC Stage IV (AJCC 8th ed.) of any histology, not amenable to curative surgery, minimal-invasive therapy or radiation therapy
- Intermediate/poor risk by IMDC (≥1 risk factors)
- ECOG 0-1
- Patients with advanced or metastatic disease occurring subsequent to initial curative nephrectomy or subsequent to other previous therapy with curative intent are eligible
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- Measurable disease as per RECIST 1.1 (at least one measurable lesion)
- Participants must be eligible to be treated with first line Nivolumab+Ipilimumab based on investigator´s judgement.
- Patients must have adequate fresh tissue available. If a fresh tissue sample is not available by routine procedures, participants must have a lesion amenable to fresh tumor biopsy at study entry for the next generation sequencing (NGS) required for this study and willing to provide informed consent for such biopsy. FFPE tumor samples are not suitable for the NGS required for this study.
- Patient is agreeable to allow tumor and blood samples to be submitted for complete exome and transcriptome sequencing.
- No previous systemic therapy for advanced or metastatic RCC
- Patients with 3 or fewer brain metastases that are < 1 cm in diameter and asymptomatic are eligible if clinically stabe
- Participants must have normal organ and bone marrow function as defined below Leukocytes ≥3,000/mcL Absolute neutrophil count ≥1,000/mcL Platelets ≥100,000/mcL Total bilirubin within 1,5 ULN AST(SGOT)/ALT(SGPT) ≤5 × institutional upper limit of normal Creatinine Clearance ≥40 mL/min/(calculated using the Cockroft-Gault equation)
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test before entry onto the trial and within 2 days prior to start of study medication.
- Female patients enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity for the duration of vaccine treatment plus 30 days (duration of ovulatory cycle).
Who cannot join
- Prior treatment with any anti-programmed cell death (anti-PD-1), or anti-programmed cell death ligand 1 (anti-PD-L1) agent or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents. Prior systemic anti-cancer therapy for curative intent with VEGFR or mTOR targeting agents is allowed if discontinued >6 months prior to enrolment.
- Prior RCC-directed cancer vaccine therapy.
- Any history of a known or suspected autoimmune disease [e.g. including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome) or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Participants with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
- Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Active brain metastases or leptomeningeal metastases
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- Positive serological test for hepatitis C virus ot hepatitis B virus surface antigen (HBsAg) or or human immunodeficiency virus (HIV)
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring IV antibiotic treatment, symptomatic congestive heart failure, unstable angina pectoris, clinically relevant cardiac arrhythmia.
- Any known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
Trial locations and contacts
1 site in 1 country.
Germany1 site
SLK Kliniken Heilbronn, Klinik für Innere Medizin III: Hämatologie, Onkologie, Palliativmedizin
Heilbronn, 74078
About this study
This is a monocenter, single-arm, prospective phase Ib trial, designed to evaluate the safety, clinical toxicity and in vivo immunological effects of a patient-individualized peptide vaccination added to standard of care checkpoint blockade (nivolumab) in adult patients with metastatic/advanced renal cell carcinoma who experienced at least stable disease after four cycles of standard of care immune therapy (ipilimumab/nivolumab).
Read the detailed description
The aim of this clinical study is to evaluate the feasibility and safety of an individualized peptide vaccination approach in patients with advanced renal cell carcinoma who experienced at least stable disease after four cycles of standard of care immune therapy (ipilimumab/nivolumab). For this purpose, tumor-specific mutations are analyzed by comparative exome sequencing of tumor and healthy reference tissue. In a second step, HLA-binding (human leukocyte antigen-binding) peptides derived from mutated protein sequences are selected for vaccination. The peptides are administered as a vaccination cocktail with adjuvant GM-CSF and Imiquimod over a course of 9 months and a total of 16 vaccinations. Primary objective is the de novo induction of a specific T cell response without unacceptable toxicity.
- Conditions
- Advanced Renal Cell Carcinoma
- Being tested
- IVAC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVACBiological
IVAC is a personalized peptide vaccine
| Study group | Role | What they receive |
|---|---|---|
| IVAC-RCC-001 | Experimental | Individual peptide vaccination with adjuvant GM-CSF and Imiquimod Intradermal injection of a cocktail of 3-5 individual HLA-binding peptides. Subcutaneous injection of adjuvant GM-CSF at vaccination site. Topical administration of Imiquimod at vaccination site. Receives: Biological: IVAC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint is "success of treatment" defined as a patient without unacceptable toxicity and showing a vaccination-induced T-cell response.
Treatment success is defined as a patient without
- unacceptable toxicities (grade 4 according to NCI-CTC) and in whom
- a vaccine-specific response of CD4+ and/or CD8+ T cells could be induced. The primary endpoint will be analyzed after 10 patients have reached visit 10
Measured: 120 days
Secondary outcomes (2)
To evaluate CD4+ and/or CD8+ T-cell responses over the vaccination period.
T-cell responses will be measured after completion of the study and will be analyzed with regard to the T-cell responses after 10 vaccinatuions /at day 120.
Measured: 246 days
To evaluate the event-free survival (EFS) during and after treatment.
EFS will be assessed on days 120 and 246.
Measured: 246 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2022
- Study start17 Oct 2022
- Primary completion15 Sep 2024
- Study completion15 Sep 2024
Why it stopped: Premature discontinuation due to üoor participant recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Renal Cell CarcinomaStudies 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- SLK Kliniken Heilbronn GmbH
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Uwe Martens, SLK Kliniken Heilbronn GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05641545
- Sponsor's protocol ID
- IVAC-RCC-001
- Status last verified
- Sep 2024
- First submitted
- 2 May 2022
- Last updated
- 19 Sep 2024
- 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 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IVAC-RCC-001: A Personalized Neoantigen Vaccine as Add-on to Standard of Care Checkpoint Inhibitor in Advanced/Metastatic RCC Patients
- ClinicalTrials.gov ID
- NCT05641545
- Acronym / sponsor ID
- IVAC-RCC-001
- Conditions
- Advanced Renal Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Premature discontinuation due to üoor participant recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- SLK Kliniken Heilbronn GmbHUniversity, hospital or other
- Study start
- 17 Oct 2022 (actual)
- Primary completion
- 15 Sep 2024 (actual)
- Study completion
- 15 Sep 2024 (actual)
- First posted
- 7 Dec 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 monocenter, single-arm, prospective phase Ib trial, designed to evaluate the safety, clinical toxicity and in vivo immunological effects of a patient-individualized peptide vaccination added to standard of care checkpoint blockade (nivolumab) in adult patients with metastatic/advanced renal cell carcinoma who experienced at least stable disease after four cycles of standard of care immune therapy (ipilimumab/nivolumab).
Detailed description
The aim of this clinical study is to evaluate the feasibility and safety of an individualized peptide vaccination approach in patients with advanced renal cell carcinoma who experienced at least stable disease after four cycles of standard of care immune therapy (ipilimumab/nivolumab). For this purpose, tumor-specific mutations are analyzed by comparative exome sequencing of tumor and healthy reference tissue. In a second step, HLA-binding (human leukocyte antigen-binding) peptides derived from mutated protein sequences are selected for vaccination. The peptides are administered as a vaccination cocktail with adjuvant GM-CSF and Imiquimod over a course of 9 months and a total of 16 vaccinations. Primary objective is the de novo induction of a specific T cell response without unacceptable toxicity.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IVAC-RCC-001 | Experimental | Biological: IVACIndividual peptide vaccination with adjuvant GM-CSF and Imiquimod Intradermal injection of a cocktail of 3-5 individual HLA-binding peptides. Subcutaneous injection of adjuvant GM-CSF at vaccination site. Topical administration of Imiquimod at vaccination site. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age 18 or older
- Ability to understand and willingness to sign a written informed consent document.
- Patients with RCC Stage IV (AJCC 8th ed.) of any histology, not amenable to curative surgery, minimal-invasive therapy or radiation therapy
- Intermediate/poor risk by IMDC (≥1 risk factors)
- ECOG 0-1
Key exclusion criteria (9 listed)
- Prior treatment with any anti-programmed cell death (anti-PD-1), or anti-programmed cell death ligand 1 (anti-PD-L1) agent or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents. Prior systemic anti-cancer therapy for curative intent with VEGFR or mTOR targeting agents is allowed if discontinued >6 months prior to enrolment.
- Prior RCC-directed cancer vaccine therapy.
- Any history of a known or suspected autoimmune disease [e.g. including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome) or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Participants with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
- Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune 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 |
|---|---|---|
| IVACIVAC is a personalized peptide vaccine | Biological | IVAC-RCC-001 |
Primary outcome
Primary endpoint is "success of treatment" defined as a patient without unacceptable toxicity and showing a vaccination-induced T-cell response.
Time frame: 120 days
Treatment success is defined as a patient without 1. unacceptable toxicities (grade 4 according to NCI-CTC) and in whom 2. a vaccine-specific response of CD4+ and/or CD8+ T cells could be induced. The primary endpoint will be analyzed after 10 patients have reached visit 10
2 secondary outcomes
To evaluate CD4+ and/or CD8+ T-cell responses over the vaccination period.
Time frame: 246 days
To evaluate the event-free survival (EFS) during and after treatment.
Time frame: 246 days
Results and safety
The study was stopped early (reason given: Premature discontinuation due to üoor participant recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 IVAC in people with Advanced Renal Cell Carcinoma, run by SLK Kliniken Heilbronn GmbH at 1 site in Germany.
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 15 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: stopped early, as of the sponsor's last update on 19 Sep 2024. 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 Germany. 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: Premature discontinuation due to üoor participant recruitment). 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?
Primary endpoint is "success of treatment" defined as a patient without unacceptable toxicity and showing a vaccination-induced T-cell response. (time frame: 120 days). 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 19 Sep 2024.