Renal Cell CarcinomaPhase 2NCT00001703
Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma
A Phase 2 study testing incomplete Freund's adjuvant and von Hippel-Lindau peptide vaccine in people with Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
About 27,000 new cases of renal cell carcinoma (RCC) are diagnosed every year in the United States. 11,000 of these cases will die from the disease. More than half of patients present with advanced or metastatic disease for which chemotherapy plays a very limited role. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- incomplete Freund's adjuvant and von Hippel-Lindau peptide vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 1998to Nov 2008
- Phase
- Phase 2
- 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
- Patients must be 18 years of age or older.
- Histologic diagnosis of renal cell carcinoma.
- Tumor tissue availability for determination of Von Hippel-Lindau (VHL) mutation (paraffin block, or fresh tissue).
- Patients must carry a VHL mutation in their tumor.
- Patients must have metastatic disease for which no further chemotherapy or radiation options, which are known to increase survival, are available.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
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- Expected survival more than 3 months.
- While measurable disease is preferable, it is not a necessity.
- The patient should not have received chemotherapy, radiation therapy, immunotherapy or steroids for at least 4 weeks prior to starting vaccination, and should have recovered from all acute toxicities of previous treatment.
- Patients must understand and sign an informed consent document that explains the neoplastic nature of his/her disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, and potential risks and toxicities.
Who cannot join
- Any condition that does not fit with the inclusion criteria.
- Any of the following: White blood cells (WBC) less than 2000/mm(3); Platelets less than 100K/mm
- (3); Creatinine greater than 2.0 mg/dl; Serum Bilirubin greater than 2.0 mg/dl, Serum glutamic oxaloacetic transaminase (SGOT), or Serum glutamic pyruvic transaminase (SGPT) greater than 4x normal.
- Human Immunodeficiency virus (HIV) or active Hepatitis B or C (i.e. detectable Hepatitis B surface (HBS) Antigen or Heteroconjugate (HC) antibodies).
- Pregnant women or nursing mothers are ineligible. Women with reproductive potential must have negative urine pregnancy test. Women of reproductive potential must use adequate contraception.
- Patients with active ischemic heart disease (i.e. Class III or IV cardiac disease)-New York Heart Association), a recent history of myocardial infarction (within the last 6 months), history of congestive heart failure, ventricular arrhythmias or other arrhythmias requiring therapy, or any other medical conditions that the principal investigators sees to be unfit for such therapy.
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- History of Central Nervous System (CNS) metastases.
- Patients with history of autoimmune disease e.g. (autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus erythematosus, Sjogren syndrome, or scleroderma; myasthenia grave's; Good pasture syndrome; Addison's disease, Hashimoto's thyroiditis, rheumatoid arthritis, multiple sclerosis, or active Graves' disease).
- If, in the opinion of the principal or associate investigators, it is not in the best medical interest of the patient to enter this study, the patient will be ineligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute, National Institutes of Health
Bethesda, Maryland, 20892
About this study
About 27,000 new cases of renal cell carcinoma (RCC) are diagnosed every year in the United States. 11,000 of these cases will die from the disease. More than half of patients present with advanced or metastatic disease for which chemotherapy plays a very limited role. Therefore, development of another therapeutic approach is needed. Cancers in humans are commonly associated with mutations in dominant and recessive oncogenes. These genes produce mutated proteins that are unique to cancer cells. Von Hipple-Lindau (VHL) gene which is associated with the development of the VHL disease, has been recently mapped and cloned, and it is found to be mutated in 57% of sporadic renal cell carcinomas.
Data in mice have shown the generation of major histocompatibility complex (MHC) restricted cytotoxic T lymphocyte (CTL) that are capable of detecting endogenous cytoplasmic peptide derived from mutated oncogenes. In addition, we have recently demonstrated, by conducting different phase I clinical trials in which we vaccinate cancer patients with mutated Ras or p53 peptides corresponding to the abnormality patients harbor in their tumors, that in some patients we can generate immunological responses represented by the generation of lymphocytes (CD4+ and/or CD8+). In the current study, we would like to extend our observations to test whether VHL tumor suppressor protein can be immunologically targeted by vaccination. We have identified specific epitopes along the amino acid sequence of the VHL protein, which represent known specific human leukocyte antigen (HLA) class-I binding motifs. These amino acids stretches in the VHL protein correspond to the area of the point mutation hot spots. Therefore, we propose to treat patients with sporadic RCC who carry VHL mutations in their tumors with corresponding mutant VHL peptide vaccination. This vaccination will be done either by using pulsed-autologous peripheral mononuclear cells with the peptides, or peptides administered subcutaneously alone or in combination with cytokines.
Read the detailed description
About 27,000 new cases of renal cell carcinoma (RCC) are diagnosed every year in the United States. 11,000 of these cases will die from the disease. More than half of patients present with advanced or metastatic disease for which chemotherapy plays a very limited role. Therefore, development of another therapeutic approach is needed. Cancers in humans are commonly associated with mutations in dominant and recessive oncogenes. These genes produce mutated proteins that are unique to cancer cells. Von Hipple-Lindau gene, which is associated with the development of the VHL disease, has been recently mapped and cloned; it is found to be mutated in 57% of sporadic renal cell carcinomas.
Data in mice have shown the generation of MHC restricted CTL that are capable of detecting endogenous cytoplasmic peptide derived from mutated oncogenes. In addition, we have recently demonstrated, by conducting different phase I clinical trials in which we vaccinate cancer patients with mutated Ras or p53 peptides corresponding to the abnormality patients harbor in their tumors, that in some patients we can generate immunological responses represented by the generation of lymphocytes (CD4+ and/or CD8+). In the current study, we would like to extend our observations to test whether VHL tumor suppressor protein can be immunologically targeted by vaccination. We have identified specific epitopes along the amino acid sequence of the VHL protein which represent known specific HLA class-I binding motifs. These amino acids stretches in the VHL protein correspond to the area of the point mutation hot spots. Therefore, this protocol treats patients with sporadic RCC who carry VHL mutations in their tumors with corresponding mutant VHL peptide vaccination.
- Conditions
- Renal Cell Carcinoma
- Being tested
- incomplete Freund's adjuvant, von Hippel-Lindau peptide vaccine
- Keywords
- Immunotherapy, Kidney, Genes, Vaccine Therapy, Renal Cell Carcinoma
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
incomplete Freund's adjuvantBiological
Also called ISA-51, Montanide ISA-51 adjuvant
0.7 ml of ISA-51 (Montanide ISA-51 adjuvant, incomplete Freund's adjuvant) will be mixed with peptide alone and injected subcutaneously every four weeks for a total of four vaccinations.
von Hippel-Lindau peptide vaccineBiological
1000 micrograms administered subcutaneously every four weeks for a total of four vaccinations.
| Study group | Role | What they receive |
|---|---|---|
| Group A-VHL peptide and ISA-51 adjuvant | Experimental | Patients are vaccinated with 1000 micrograms of the mutant Von Hipple-Lindau (VHL) peptide administered subcutaneously along with ISA-51 adjuvant (Montanide ISA-51 adjuvant, Incomplete Freund's adjuvant) and injected subcutaneously every four weeks for a total of four vaccinations. Receives: Biological: incomplete Freund's adjuvant; Biological: von Hippel-Lindau peptide vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Generated an Immune Response
The immunological response was assessed by in-vitro T cell cytokine production enzyme-linked immunosorbent spot (ELISPOT). From each patients, post-vaccination peripheral blood mononuclear cells (PBMC) were compared to pre-vaccination as a baseline. A positive ELISPOT result for the patients was defined as a total number of experimental spots in the post-vaccination sample of more than twofold above the total spots in the pre-vaccination sample.
Measured: 30 months
Secondary outcomes (1)
The Number of Participants With Adverse Events.
Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Measured: 88 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startAug 1998
- Primary completionNov 2008
- Study completionNov 2008
Why it stopped: Due to poor accrual and lack of peptide vaccine
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 (3)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Samir N Khleif, M.D., Principal investigator, National Cancer Institute, National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001703
- Sponsor's protocol ID
- 980139
- Other IDs
- 98-C-0139, 98-C-0139
- Status last verified
- Jul 2014
- First submitted
- 3 Nov 1999
- Last updated
- 25 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Stahl M, Wilke HJ, Seeber S, Schmoll HJ. Cytokines and cytotoxic agents in renal cell carcinoma: a review. Semin Oncol. 1992 Apr;19(2 Suppl 4):70-9. No abstract available.
PubMed 1553577Stadler WM, Vogelzang NJ. Low-dose interleukin-2 in the treatment of metastatic renal-cell carcinoma. Semin Oncol. 1995 Feb;22(1):67-73. No abstract available.
PubMed 7855621Parkinson DR, Sznol M. High-dose interleukin-2 in the therapy of metastatic renal-cell carcinoma. Semin Oncol. 1995 Feb;22(1):61-6. No abstract available.
PubMed 7855620
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00001703
- Acronym / sponsor ID
- 980139
- Conditions
- Renal Cell Carcinoma
- Keywords
- Immunotherapy, Kidney, Genes, Vaccine Therapy, Renal Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to poor accrual and lack of peptide vaccine
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Aug 1998
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Posted 14 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
About 27,000 new cases of renal cell carcinoma (RCC) are diagnosed every year in the United States. 11,000 of these cases will die from the disease. More than half of patients present with advanced or metastatic disease for which chemotherapy plays a very limited role. Therefore, development of another therapeutic approach is needed. Cancers in humans are commonly associated with mutations in dominant and recessive oncogenes. These genes produce mutated proteins that are unique to cancer cells. Von Hipple-Lindau (VHL) gene which is associated with the development of the VHL disease, has been recently mapped and cloned, and it is found to be mutated in 57% of sporadic renal cell carcinomas.
Data in mice have shown the generation of major histocompatibility complex (MHC) restricted cytotoxic T lymphocyte (CTL) that are capable of detecting endogenous cytoplasmic peptide derived from mutated oncogenes. In addition, we have recently demonstrated, by conducting different phase I clinical trials in which we vaccinate cancer patients with mutated Ras or p53 peptides corresponding to the abnormality patients harbor in their tumors, that in some patients we can generate immunological responses represented by the generation of lymphocytes (CD4+ and/or CD8+). In the current study, we would like to extend our observations to test whether VHL tumor suppressor protein can be immunologically targeted by vaccination. We have identified specific epitopes along the amino acid sequence of the VHL protein, which represent known specific human leukocyte antigen (HLA) class-I binding motifs. These amino acids stretches in the VHL protein correspond to the area of the point mutation hot spots. Therefore, we propose to treat patients with sporadic RCC who carry VHL mutations in their tumors with corresponding mutant VHL peptide vaccination. This vaccination will be done either by using pulsed-autologous peripheral mononuclear cells with the peptides, or peptides administered subcutaneously alone or in combination with cytokines.
Detailed description
About 27,000 new cases of renal cell carcinoma (RCC) are diagnosed every year in the United States. 11,000 of these cases will die from the disease. More than half of patients present with advanced or metastatic disease for which chemotherapy plays a very limited role. Therefore, development of another therapeutic approach is needed. Cancers in humans are commonly associated with mutations in dominant and recessive oncogenes. These genes produce mutated proteins that are unique to cancer cells. Von Hipple-Lindau gene, which is associated with the development of the VHL disease, has been recently mapped and cloned; it is found to be mutated in 57% of sporadic renal cell carcinomas.
Data in mice have shown the generation of MHC restricted CTL that are capable of detecting endogenous cytoplasmic peptide derived from mutated oncogenes. In addition, we have recently demonstrated, by conducting different phase I clinical trials in which we vaccinate cancer patients with mutated Ras or p53 peptides corresponding to the abnormality patients harbor in their tumors, that in some patients we can generate immunological responses represented by the generation of lymphocytes (CD4+ and/or CD8+). In the current study, we would like to extend our observations to test whether VHL tumor suppressor protein can be immunologically targeted by vaccination. We have identified specific epitopes along the amino acid sequence of the VHL protein which represent known specific HLA class-I binding motifs. These amino acids stretches in the VHL protein correspond to the area of the point mutation hot spots. Therefore, this protocol treats patients with sporadic RCC who carry VHL mutations in their tumors with corresponding mutant VHL peptide vaccination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group A-VHL peptide and ISA-51 adjuvant | Experimental | Biological: incomplete Freund's adjuvant, Biological: von Hippel-Lindau peptide vaccinePatients are vaccinated with 1000 micrograms of the mutant Von Hipple-Lindau (VHL) peptide administered subcutaneously along with ISA-51 adjuvant (Montanide ISA-51 adjuvant, Incomplete Freund's adjuvant) and injected subcutaneously every four weeks for a total of four vaccinations. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must be 18 years of age or older.
- Histologic diagnosis of renal cell carcinoma.
- Tumor tissue availability for determination of Von Hippel-Lindau (VHL) mutation (paraffin block, or fresh tissue).
- Patients must carry a VHL mutation in their tumor.
- Patients must have metastatic disease for which no further chemotherapy or radiation options, which are known to increase survival, are available.
Key exclusion criteria (9 listed)
- Any condition that does not fit with the inclusion criteria.
- Any of the following: White blood cells (WBC) less than 2000/mm(3); Platelets less than 100K/mm
- (3); Creatinine greater than 2.0 mg/dl; Serum Bilirubin greater than 2.0 mg/dl, Serum glutamic oxaloacetic transaminase (SGOT), or Serum glutamic pyruvic transaminase (SGPT) greater than 4x normal.
- Human Immunodeficiency virus (HIV) or active Hepatitis B or C (i.e. detectable Hepatitis B surface (HBS) Antigen or Heteroconjugate (HC) antibodies).
- Pregnant women or nursing mothers are ineligible. Women with reproductive potential must have negative urine pregnancy test. Women of reproductive potential must use adequate contraception.
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 |
|---|---|---|
| incomplete Freund's adjuvantAlso: ISA-51, Montanide ISA-51 adjuvant0.7 ml of ISA-51 (Montanide ISA-51 adjuvant, incomplete Freund's adjuvant) will be mixed with peptide alone and injected subcutaneously every four weeks for a total of four vaccinations. | Biological | Group A-VHL peptide and ISA-51 adjuvant |
| von Hippel-Lindau peptide vaccine1000 micrograms administered subcutaneously every four weeks for a total of four vaccinations. | Biological | Group A-VHL peptide and ISA-51 adjuvant |
Primary outcome
Percentage of Participants Who Generated an Immune Response
Time frame: 30 months
The immunological response was assessed by in-vitro T cell cytokine production enzyme-linked immunosorbent spot (ELISPOT). From each patients, post-vaccination peripheral blood mononuclear cells (PBMC) were compared to pre-vaccination as a baseline. A positive ELISPOT result for the patients was defined as a total number of experimental spots in the post-vaccination sample of more than twofold above the total spots in the pre-vaccination sample.
1 secondary outcome
The Number of Participants With Adverse Events.
Time frame: 88 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 1553577Stahl M, Wilke HJ, Seeber S, Schmoll HJ. Cytokines and cytotoxic agents in renal cell carcinoma: a review. Semin Oncol. 1992 Apr;19(2 Suppl 4):70-9. No abstract available.
- Background: PubMed 7855621Stadler WM, Vogelzang NJ. Low-dose interleukin-2 in the treatment of metastatic renal-cell carcinoma. Semin Oncol. 1995 Feb;22(1):67-73. No abstract available.
- Background: PubMed 7855620Parkinson DR, Sznol M. High-dose interleukin-2 in the therapy of metastatic renal-cell carcinoma. Semin Oncol. 1995 Feb;22(1):61-6. No abstract available.
- Genetics Home ReferenceLink provided by the sponsor.
- MedlinePlusLink provided by the sponsor.
- Drug InformationLink provided by the sponsor.
- U.S. FDA ResourcesLink provided by the sponsor.
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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.
Samir N Khleif, M.D. principal investigator
National Cancer Institute, National Institutes of Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing incomplete Freund's adjuvant and von Hippel-Lindau peptide vaccine in people with Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
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 10 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 25 Jul 2014. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 14 Jun 2012). 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?
Percentage of Participants Who Generated an Immune Response (time frame: 30 months). 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 NCT00001703, which also lists 3 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 25 Jul 2014.