MelanomaPhase 1NCT00623831
A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen
A Phase 1 study testing Mixed bacterial vaccine in people with Melanoma and Sarcoma, run by Ludwig Institute for Cancer Research at 1 site in Germany.
Trial summary
This was a phase 1, open-label, multiple dose, single-arm study. The mixed bacteria vaccine (MBV) was administered at a starting dose of 250 EU (1 µL) and escalated in each subject to a dose inducing the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Sarcoma, Gastrointestinal Stromal Tumor (GIST)
- What is being tested?
- Mixed bacterial vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteGermany
- Study dates
- May 2007to May 2013
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell carcinoma, sarcoma, gastrointestinal stroma tumor (GIST) or prostate cancer.
- Tumor expression of NY-ESO-1 by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry.
- Expected survival of at least 6 months.
- Karnofsky performance status ≥ 70%.
- Fully recovered from surgery.
- Declined, intolerated or completed standard therapy defined as follows for each tumor entity:
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- Melanoma - resistance or intolerance to dacarbazine.
- Sarcoma - resistance or intolerance to anthracyclines and to one platinum-containing chemotherapy regimen, no indication for irradiation.
- GIST - failure or intolerance of imatinib and sunitinib.
- Head and neck cancer - no indication for irradiation, resistance or intolerance to platinum-containing chemotherapy.
- Transitional cell carcinoma - resistance or intolerance to cisplatin combined with gemcitabine.
- Prostate cancer- failure of antihormonal treatment and resistance or intolerance to docetaxel.
- Ovarian carcinoma - failure of standard chemotherapy consisting of a platinum agent combined with a taxane and of an anthracycline.
- Esophageal cancer - failure of standard chemotherapy consisting of a platinum agent.
- Breast cancer- failure or intolerance of standard first-, second- and third-line chemotherapy consisting of a taxane and anthracycline. No indication or resistance to standard antihormonal treatment. No indication or resistance to human epidermal growth factor receptor (HER)-2-neu targeted therapy. No indication or resistance to irradiation and/or surgery.
- Within the last 2 weeks prior to study day 1, vital laboratory parameters must have been within the normal range, except for the following laboratory parameters, which must have been within the ranges specified:
- Absolute neutrophil count (ANC): ≥ 1,000/mm3
- Platelet count: ≥ 75,000/mm3
- Alanine aminotransferase (ALT): ≤ 5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST): ≤ 5 x ULN
- Total bilirubin: ≤ 2.5 x ULN
- Creatinine: ≤ 2 mg/dL
- Age ≥ 18 years.
- Able and willing to give written informed consent.
Who cannot join
- Clinically significant heart disease (New York Heart Association Class III or IV).
- Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
- Subjects with serious intercurrent illness requiring hospitalization.
- Known human immunodeficiency virus positivity.
- Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).
- Known autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus), as these conditions might have interfered with the evaluation of the induced immune response. Subjects with vitiligo or melanoma-associated hypopigmentation were not excluded.
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- Chronic use of immunosuppressive drugs such as systemic corticosteroids.
- Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
- Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
- Lack of availability for immunological and clinical follow-up assessments.
- Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent.
- Pregnancy or breastfeeding.
- Women of childbearing potential: Refusal or inability to use effective means of contraception.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen.
This was a phase 1, open-label, multiple dose, single-arm study. The mixed bacteria vaccine (MBV) was administered at a starting dose of 250 EU (1 µL) and escalated in each subject to a dose inducing the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. The primary objective was to determine the safety profile of MBV in subjects with malignant tumors that expressed the NY-ESO-1 antigen and to identify the dose that induced the desired pyrogenic effect. Secondary objectives were to evaluate the immunological effects and tumor response of subjects following vaccination.
Read the detailed description
Subjects in Cohort 1 were enrolled to receive MBV subcutaneously at a starting dose of 250 EU (1 µL; dose level 1) administered twice weekly. In the absence of a dose-limiting toxicity (DLT), the MBV dose was escalated in each subject to the MBV dose that elicited the desired pyrogenic effect, or up to the maximum dose of 547,000 EU (dose level 8). Once the desired pyrogenic effect was observed, subjects received MBV twice weekly for 4 doses at the pyrogenic dose level.
Subjects in Cohort 2 were enrolled to receive MBV at the pyrogenic dose level (determined to be 60,800 EU [dose level 6]) twice weekly for 6 weeks. Vaccinations were injected intralesionally if possible and subcutaneously if intralesional injection was not possible. If a fever of 39.5°C to 40°C was observed, the subject's dose was reduced to dose level 5 (20,300 EU [81 μL]).
Subjects were observed at the clinic for up to 6 hours following each vaccination, with vital signs measured hourly. At baseline and throughout the study, subjects were assessed for NY-ESO-1-specific humoral and cellular immunity, chemistry, hematology, and cytokine analysis (interleukin [IL]-1, IL-6, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α). Safety was monitored continuously throughout the study.
- Conditions
- Melanoma, Sarcoma, Gastrointestinal Stromal Tumor (GIST), Head and Neck Cancer, Transitional Cell Carcinoma, Prostate Cancer
- Being tested
- Mixed bacterial vaccine
- Keywords
- MBV, Mixed Bacterial Vaccine, NY-ESO-1
- Medical subject headings
- Melanoma, Sarcoma, Gastrointestinal Stromal Tumors, Head and Neck Neoplasms, Carcinoma, Transitional Cell, Prostatic Neoplasms, Ovarian Neoplasms, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mixed bacterial vaccineBiological
Also called MBV
MBV was administered twice weekly by subcutaneous injection in Cohort 1 and by intralesional (preferred) or subcutaneous (if intralesional not possible) injection in Cohort 2. In Cohort 1, the MBV starting dose was 250 EU (dose level 1) with possible intrasubject escalations up to 547,000 EU (dose level 8). In Cohort 2, all subjects received MBV at a fixed dose of 60,800 EU (dose level 6).
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects received MBV at a starting dose of 250 EU (dose level 1) twice weekly, with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed. The maximum possible dose to be investigated was 547,000 EU (dose level 8). Receives: Biological: Mixed bacterial vaccine |
| Cohort 2 | Experimental | Subjects received MBV twice weekly at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1. Receives: Biological: Mixed bacterial vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.
Measured: Up to 3 months
Number of Participants With Pyrogenicity at Each Dose Level Tested in the Intrasubject Dose Escalation Performed Over a Dose Range of 250 to 547,000 EU
Intrasubject dose escalation performed over a dose range of 250 to 547,000 EU until achievement of the desired pyrogenic effects (i.e., body temperature increase to 38°C to 39.5°C). Of note, the median pyrogenic dose was 60,800 EU.
Measured: Weeks 1 through 6
Secondary outcomes (2)
Number of Participants With Serum NY-ESO-1-specific Immune Responses
Serum NY-ESO-1-specific immune responses evaluated by humoral immunity (antibodies measured by ELISA), cellular immunity (CD8+ T-cell and CD4+ T-cell measured by ELISPOT), and cytokine activation (measured by ELISA) from pre-treatment through 4 weeks after the last dose of study treatment. [Note: CD = cluster of differentiation; IFN =interferon; IL = interleukin; TNF = tumor necrosis factor]
Measured: Up to 3 months
Number of Participants With Best Overall Tumor Response
Tumor responses evaluated using computed tomography and categorized according to RECIST version 1.0 at pre-treatment and 4 weeks after the last dose of study treatment. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions [no evidence of disease]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Measured: Up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2008 (estimated)
- Study startMay 2007
- Primary completionMay 2012
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies 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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- Krankenhaus Nordwest
- Responsible party
- Sponsor
- Investigators
- Elke Jager, MD, Principal investigator, Krankenhaus Nordwest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00623831
- Sponsor's protocol ID
- LUD2005-003
- Other IDs
- 2006-002015-27
- Status last verified
- Oct 2022
- First submitted
- 4 Feb 2008
- Last updated
- 25 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data have been published
Publications
Karbach J, Neumann A, Brand K, Wahle C, Siegel E, Maeurer M, Ritter E, Tsuji T, Gnjatic S, Old LJ, Ritter G, Jager E. Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity. Clin Cancer Res. 2012 Oct 1;18(19):5449-59. doi: 10.1158/1078-0432.CCR-12-1116. Epub 2012 Jul 30.
PubMed 22847809
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen.
- ClinicalTrials.gov ID
- NCT00623831
- Acronym / sponsor ID
- LUD2005-003
- Conditions
- Melanoma, Sarcoma, Gastrointestinal Stromal Tumor (GIST), Head and Neck Cancer, Transitional Cell Carcinoma, Prostate Cancer
- Keywords
- MBV, Mixed Bacterial Vaccine, NY-ESO-1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- Krankenhaus Nordwest
- Study start
- May 2007
- Primary completion
- May 2012 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 26 Feb 2008 (estimated)
- Results
- Posted 9 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a phase 1, open-label, multiple dose, single-arm study. The mixed bacteria vaccine (MBV) was administered at a starting dose of 250 EU (1 µL) and escalated in each subject to a dose inducing the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. The primary objective was to determine the safety profile of MBV in subjects with malignant tumors that expressed the NY-ESO-1 antigen and to identify the dose that induced the desired pyrogenic effect. Secondary objectives were to evaluate the immunological effects and tumor response of subjects following vaccination.
Detailed description
Subjects in Cohort 1 were enrolled to receive MBV subcutaneously at a starting dose of 250 EU (1 µL; dose level 1) administered twice weekly. In the absence of a dose-limiting toxicity (DLT), the MBV dose was escalated in each subject to the MBV dose that elicited the desired pyrogenic effect, or up to the maximum dose of 547,000 EU (dose level 8). Once the desired pyrogenic effect was observed, subjects received MBV twice weekly for 4 doses at the pyrogenic dose level.
Subjects in Cohort 2 were enrolled to receive MBV at the pyrogenic dose level (determined to be 60,800 EU [dose level 6]) twice weekly for 6 weeks. Vaccinations were injected intralesionally if possible and subcutaneously if intralesional injection was not possible. If a fever of 39.5°C to 40°C was observed, the subject's dose was reduced to dose level 5 (20,300 EU [81 μL]).
Subjects were observed at the clinic for up to 6 hours following each vaccination, with vital signs measured hourly. At baseline and throughout the study, subjects were assessed for NY-ESO-1-specific humoral and cellular immunity, chemistry, hematology, and cytokine analysis (interleukin [IL]-1, IL-6, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α). Safety was monitored continuously throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Mixed bacterial vaccineSubjects received MBV at a starting dose of 250 EU (dose level 1) twice weekly, with intrasubject dose escalations for each subsequent administration in the absence of a DLT until the desired pyrogenic effect was observed. The maximum possible dose to be investigated was 547,000 EU (dose level 8). |
| Cohort 2 | Experimental | Biological: Mixed bacterial vaccineSubjects received MBV twice weekly at the fixed dose (60,800 EU [dose level 6]) that was determined to be the pyrogenic dose level in Cohort 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell carcinoma, sarcoma, gastrointestinal stroma tumor (GIST) or prostate cancer.
- Tumor expression of NY-ESO-1 by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, preferably, or immunohistochemistry.
- Expected survival of at least 6 months.
- Karnofsky performance status ≥ 70%.
- Fully recovered from surgery.
Key exclusion criteria (13 listed)
- Clinically significant heart disease (New York Heart Association Class III or IV).
- Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
- Subjects with serious intercurrent illness requiring hospitalization.
- Known human immunodeficiency virus positivity.
- Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).
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 |
|---|---|---|
| Mixed bacterial vaccineAlso: MBVMBV was administered twice weekly by subcutaneous injection in Cohort 1 and by intralesional (preferred) or subcutaneous (if intralesional not possible) injection in Cohort 2. In Cohort 1, the MBV starting dose was 250 EU (dose level 1) with possible intrasubject escalations up to 547,000 EU (dose level 8). In Cohort 2, all subjects received MBV at a fixed dose of 60,800 EU (dose level 6). | Biological | Cohort 1, Cohort 2 |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 3 months
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs from pre-treatment through 4 weeks after the last dose of study treatment.
Number of Participants With Pyrogenicity at Each Dose Level Tested in the Intrasubject Dose Escalation Performed Over a Dose Range of 250 to 547,000 EU
Time frame: Weeks 1 through 6
Intrasubject dose escalation performed over a dose range of 250 to 547,000 EU until achievement of the desired pyrogenic effects (i.e., body temperature increase to 38°C to 39.5°C). Of note, the median pyrogenic dose was 60,800 EU.
2 secondary outcomes
Number of Participants With Serum NY-ESO-1-specific Immune Responses
Time frame: Up to 3 months
Number of Participants With Best Overall Tumor Response
Time frame: Up to 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22847809Karbach J, Neumann A, Brand K, Wahle C, Siegel E, Maeurer M, Ritter E, Tsuji T, Gnjatic S, Old LJ, Ritter G, Jager E. Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity. Clin Cancer Res. 2012 Oct 1;18(19):5449-59. doi: 10.1158/1078-0432.CCR-12-1116. Epub 2012 Jul 30.
- Individual participant dataSharing planned: Yes. Data have been published
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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.
Elke Jager, MD principal investigator
Krankenhaus Nordwest
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 Mixed bacterial vaccine in people with Melanoma and Sarcoma, run by Ludwig Institute for Cancer Research 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 24 inclusion and 13 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 25 Oct 2022. 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?
Yes. Results are posted in the registry (first posted 9 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: Up to 3 months). The study lists 2 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 NCT00623831, which also lists 1 linked publication.
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 25 Oct 2022.