Ovarian NeoplasmPhase 2NCT00001827
p53 Vaccine for Ovarian Cancer
A Phase 2 study testing aldesleukin, incomplete Freund's adjuvant and p53 peptide vaccine in people with Ovarian Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will examine whether vaccination with a p53 peptide can boost an immune response to ovarian cancer and what the side effects are of the vaccine. Many patients with ovarian cancer have an altered (mutated) gene called p53 that causes the production of abnormal proteins found in their tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Neoplasm
- What is being tested?
- aldesleukin, incomplete Freund's adjuvant and p53 peptide vaccine
- Type of treatment
- Vaccines, Surgery or procedure
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jul 1999to 25 Jan 2013
- Phase
- Phase 2
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be 18 years of age or older.
- Histologic diagnosis of adenocarcinoma of the ovary.
- Tumor tissue availability for determination of p53 protein expression and genetic mutation (paraffin block, or fresh tissue).
- Immunohistochemical analysis of the tumor must demonstrate positive p53 staining.
- Patients should have ovarian cancer with marker only disease or patients with stage III, IV or recurrent who are NED post therapy.
- ECOG performance status of 1 or 0.
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- Expected survival of more than 3 months.
- The patients should not have received chemotherapy, radiation therapy, immunotherapy or systemic doses of steroids for at least 4 weeks prior to starting vaccination. And the patient should have recovered from all acute toxicities of previous treatment. Patients who received bone marrow transplantation within a year will not be eligible for the trial.
- 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.
- Patients should have HLA-A2.1 haplotype.
Who cannot join
- Any condition that does not fit with the eligibility criteria.
- Any of the following:
- Platelets less than 100K/mm(3)
- Creatinine greater than 2.0 mg/dl
- Serum Bilirubin greater than 2.0 mg/dl, SGOT, or SGPT greater than 4 times normal
- HIV or Hepatitis B or C (i.e. detectable HBS Antigen or HC Ab) since these conditions might have an effect on the immune system.
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- Pregnant women or nursing mothers are ineligible since the effect of this investigational treatment on the health of the embryo is not known. Women with reproductive potential must have negative pregnancy test and 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 arrythmias or other arrythmias requiring therapy.
- Second malignancy (within the past 2 years) other than curatively treated carcinoma in-situ of cervix or basal cell carcinoma of the skin. These patients will be excluded for the possibility of the existence of a different mutation in the other primary malignancy.
- History of CNS metastases.
- Patients with underlying immune deficiency or history of autoimmune disease e.g. (autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus erythematosus, Sjogren syndrome, or scleroderma; myasthenia gravis; Goodpasture syndrome; Addison's disease, Hashimoto's thyroiditis, active Graves' disease, or other diseases which qualify as autoimmune in origin).
- Patients with active infections requiring antibiotics. Patients requiring chronic suppressive antibiotics will be eligible for the trial.
- 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 Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low Burden Adenocarcinoma of the Ovary
This study will examine whether vaccination with a p53 peptide can boost an immune response to ovarian cancer and what the side effects are of the vaccine.
Many patients with ovarian cancer have an altered (mutated) gene called p53 that causes the production of abnormal proteins found in their tumor cells. The body s immune system may try, unsuccessfully, to fight these abnormal proteins. In this study, ovarian cancer patients with a p53 abnormality will be vaccinated with a p53 peptide a part of the same abnormal protein found in their tumor to try to boost their body s immune response to the cancer.
Read more
Patients will be divided into two groups. Group A will have four p53 peptide vaccinations three weeks apart, injected under the skin. The injection will include a drug called ISA-51, which increases the effect of the vaccine. This group will also receive two other drugs that boost the immune system, IL-2 and GM-CSF. Group B will have four p53 peptide vaccinations three weeks apart. The peptide will be mixed with the patient s own blood cells and infused into a vein. This group will also receive IL-2, but not GM-CSF.
All study candidates will be tested to see if their cancer has a p53 abnormality and if their immune system mounted a defense against it. These tests may include a tumor biopsy (removal of a small part of the tumor for microscopic examination); lymphapheresis (a procedure to take blood, remove white blood cells called lymphocytes, and return the red cells); and an immune response test similar to a skin test for tuberculosis. During the study, patients will have additional skin tests and blood tests.
Read the detailed description
P53 is the most commonly mutated gene in human cancers; it has been found to be mutated in almost 50% of ovarian cancers. Genetic mutation of p53 results in stabilization and increase in the level of the protein. In some cases, overexpression of p53 protein could also occur in tumors without detectable mutation in the open reading frame. Therefore, p53 could function as an antigen through two different mechanisms, as a mutant "foreign" protein and as a selfoverexpressed protein. The p53:264 - 272 wild type peptide has been shown to have high affinity for HLA-A2. It has also been shown to be naturally processed and endogenously
presented by HLA-A2 in different types of tumor cell lines for CTL recognition. These CTL
were able to lyse tumor cells overexpressing wild type or mutant p53 protein and failed to lyse
normal cells expressing normal levels of wild type p53.
In this protocol we will be vaccinating HLA-A2+ ovarian cancer patients who carry tumors which overexpress p53 with the wild type p53 peptide (264-272). This will be given either subcutaneously admixed with ISA-51 and GM-CSF adjuvants, or intravenously pulsed on dendritic cells along with low dose subcutaneous IL-2. In addition, those patients who express mutant p53 may also be vaccinated with a mutant p53 peptide, which corresponds to the mutation they harbor in their tumor, should the patients progress on the p53 (264-272) peptide.
- Conditions
- Ovarian Neoplasm
- Being tested
- aldesleukin, incomplete Freund's adjuvant, p53 peptide vaccine, sargramostim, therapeutic autologous dendritic cells
- Keywords
- Immunotherapy, Cancer, Oncogenes, T-cells, Vaccine Therapy, p53 Peptide, Ovarian Cancer
- Medical subject headings
- Ovarian Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aldesleukinBiological
incomplete Freund's adjuvantBiological
p53 peptide vaccineBiological
sargramostimBiological
therapeutic autologous dendritic cellsBiological
in vitro-treated peripheral blood stem cell transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular immunity as measured by Elispot assay and 51 Cr-release assay at baseline and every 3 weeks.
Secondary outcomes (1)
Toxicity as measured by Common Toxicity Criteria v2.0 at baseline and every 3 weeks.
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 start26 Jul 1999
- Primary completion17 Dec 2007
- Study completion25 Jan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ovarian NeoplasmStudies 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
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jay A Berzofsky, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001827
- Sponsor's protocol ID
- 990137
- Other IDs
- 99-C-0137
- Status last verified
- 25 Jan 2013
- First submitted
- 3 Nov 1999
- Last updated
- 6 Oct 2017
- Results posted
- No
Publications
Takahashi H, Merli S, Putney SD, Houghten R, Moss B, Germain RN, Berzofsky JA. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science. 1989 Oct 6;246(4926):118-21. doi: 10.1126/science.2789433.
PubMed 2789433Chiba I, Takahashi T, Nau MM, D'Amico D, Curiel DT, Mitsudomi T, Buchhagen DL, Carbone D, Piantadosi S, Koga H, et al. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene. 1990 Oct;5(10):1603-10.
PubMed 1979160Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D'Amico D, Bodner S, Oie HK, Linnoila RI, Mulshine JL, Minna JD, et al. p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene. 1992 Jan;7(1):171-80.
PubMed 1311061
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low Burden Adenocarcinoma of the Ovary
- ClinicalTrials.gov ID
- NCT00001827
- Acronym / sponsor ID
- 990137
- Conditions
- Ovarian Neoplasm
- Keywords
- Immunotherapy, Cancer, Oncogenes, T-cells, Vaccine Therapy, p53 Peptide, Ovarian Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 26 Jul 1999
- Primary completion
- 17 Dec 2007 (actual)
- Study completion
- 25 Jan 2013 (actual)
- First posted
- 4 Nov 1999 (estimated)
- 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 study will examine whether vaccination with a p53 peptide can boost an immune response to ovarian cancer and what the side effects are of the vaccine.
Many patients with ovarian cancer have an altered (mutated) gene called p53 that causes the production of abnormal proteins found in their tumor cells. The body s immune system may try, unsuccessfully, to fight these abnormal proteins. In this study, ovarian cancer patients with a p53 abnormality will be vaccinated with a p53 peptide a part of the same abnormal protein found in their tumor to try to boost their body s immune response to the cancer.
Patients will be divided into two groups. Group A will have four p53 peptide vaccinations three weeks apart, injected under the skin. The injection will include a drug called ISA-51, which increases the effect of the vaccine. This group will also receive two other drugs that boost the immune system, IL-2 and GM-CSF. Group B will have four p53 peptide vaccinations three weeks apart. The peptide will be mixed with the patient s own blood cells and infused into a vein. This group will also receive IL-2, but not GM-CSF.
All study candidates will be tested to see if their cancer has a p53 abnormality and if their immune system mounted a defense against it. These tests may include a tumor biopsy (removal of a small part of the tumor for microscopic examination); lymphapheresis (a procedure to take blood, remove white blood cells called lymphocytes, and return the red cells); and an immune response test similar to a skin test for tuberculosis. During the study, patients will have additional skin tests and blood tests.
Detailed description
P53 is the most commonly mutated gene in human cancers; it has been found to be mutated in almost 50% of ovarian cancers. Genetic mutation of p53 results in stabilization and increase in the level of the protein. In some cases, overexpression of p53 protein could also occur in tumors without detectable mutation in the open reading frame. Therefore, p53 could function as an antigen through two different mechanisms, as a mutant "foreign" protein and as a selfoverexpressed protein. The p53:264 - 272 wild type peptide has been shown to have high affinity for HLA-A2. It has also been shown to be naturally processed and endogenously
presented by HLA-A2 in different types of tumor cell lines for CTL recognition. These CTL
were able to lyse tumor cells overexpressing wild type or mutant p53 protein and failed to lyse
normal cells expressing normal levels of wild type p53.
In this protocol we will be vaccinating HLA-A2+ ovarian cancer patients who carry tumors which overexpress p53 with the wild type p53 peptide (264-272). This will be given either subcutaneously admixed with ISA-51 and GM-CSF adjuvants, or intravenously pulsed on dendritic cells along with low dose subcutaneous IL-2. In addition, those patients who express mutant p53 may also be vaccinated with a mutant p53 peptide, which corresponds to the mutation they harbor in their tumor, should the patients progress on the p53 (264-272) peptide.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- 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 adenocarcinoma of the ovary.
- Tumor tissue availability for determination of p53 protein expression and genetic mutation (paraffin block, or fresh tissue).
- Immunohistochemical analysis of the tumor must demonstrate positive p53 staining.
- Patients should have ovarian cancer with marker only disease or patients with stage III, IV or recurrent who are NED post therapy.
Key exclusion criteria (13 listed)
- Any condition that does not fit with the eligibility criteria.
- Platelets less than 100K/mm(3)
- Creatinine greater than 2.0 mg/dl
- Serum Bilirubin greater than 2.0 mg/dl, SGOT, or SGPT greater than 4 times normal
- HIV or Hepatitis B or C (i.e. detectable HBS Antigen or HC Ab) since these conditions might have an effect on the immune system.
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 |
|---|---|---|
| aldesleukin | Biological | – |
| incomplete Freund's adjuvant | Biological | – |
| p53 peptide vaccine | Biological | – |
| sargramostim | Biological | – |
| therapeutic autologous dendritic cells | Biological | – |
| in vitro-treated peripheral blood stem cell transplantation | Procedure or surgery | – |
Primary outcome
Cellular immunity as measured by Elispot assay and 51 Cr-release assay at baseline and every 3 weeks.
1 secondary outcome
Toxicity as measured by Common Toxicity Criteria v2.0 at baseline and every 3 weeks.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2017.
- Background: PubMed 2789433Takahashi H, Merli S, Putney SD, Houghten R, Moss B, Germain RN, Berzofsky JA. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science. 1989 Oct 6;246(4926):118-21. doi: 10.1126/science.2789433.
- Background: PubMed 1979160Chiba I, Takahashi T, Nau MM, D'Amico D, Curiel DT, Mitsudomi T, Buchhagen DL, Carbone D, Piantadosi S, Koga H, et al. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene. 1990 Oct;5(10):1603-10.
- Background: PubMed 1311061Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D'Amico D, Bodner S, Oie HK, Linnoila RI, Mulshine JL, Minna JD, et al. p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene. 1992 Jan;7(1):171-80.
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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.
Jay A Berzofsky, M.D. principal investigator
National Cancer Institute (NCI)
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 aldesleukin, incomplete Freund's adjuvant and p53 peptide vaccine in people with Ovarian Neoplasm, 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 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: stopped early, as of the sponsor's last update on 6 Oct 2017. 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?
The study was stopped early. 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?
Cellular immunity as measured by Elispot assay and 51 Cr-release assay at baseline and every 3 weeks.. 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 NCT00001827, 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 6 Oct 2017.