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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00009958

Vaccine Therapy With or Without Sargramostim in Treating Patients With Cancer

A Phase 1 study testing recombinant fowlpox-CEA(6D)/TRICOM vaccine, recombinant vaccinia-CEA(6D)-TRICOM vaccine and sargramostim in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Phase I trial to compare the effectiveness of vaccine therapy with or without sargramostim in treating patients who have solid tumors. Vaccines may make the body build an immune response to kill tumor cells. Combining colony-stimulating factors such as sargramostim with vaccines may kill more tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
recombinant fowlpox-CEA(6D)/TRICOM vaccine, recombinant vaccinia-CEA(6D)-TRICOM vaccine and sargramostim
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
Nov 2000to Apr 2010
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

  • Patients must have a histologically confirmed diagnosis of malignancy, with evidence of metastatic disease (evaluable disease is adequate), who have not responded to standard therapy, who have relapsed, or for whom such therapy is not available
  • Patients must have a tumor that has been shown to express CEA by immunohistochemical techniques or have had an elevated serum CEA > 10 at any point during their disease course
  • Patients must have an anticipated survival of at least 6 months
  • Patients must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent
  • Patients must be ambulatory, with an ECOG performance status of 0 or 1, and must be maintaining a reasonable state of nutrition, consistent with weight maintenance
  • WBC >= 3,000/mm^3
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  • ANC >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Bilirubin =< 2 x upper limit of normal
  • SGOT and SGPT =< 4 x upper limit of normal
  • All patients should have an initial urine analysis; the initial urine analysis for eligibility is: proteinuria grade 0, hematuria grade 0, and no abnormal sediment; any positive protein including trace values should be evaluated by a 24-hour urine; any other abnormality in the sediment or the presence of hematuria should be evaluated by a nephrologist for evidence of underlying renal pathology; patients may be eligible if the underlying cause of the abnormality is determined to be non-renal
  • Normal creatinine is defined by creatinine =< 1.5 mg/dL OR creatinine clearance >= 60 ml/min
  • At least 6 patients must be HLA-A2 positive for each of cohorts 3, 6, and 7; once the HLA-A2 positive quota of 6 has been met, enrollment to that cohort may close at the discretion of the principal investigator; there are no HLA phenotype restrictions for cohorts 1,2,4, and 5, although phenotyping will be performed on all patients
  • Vaccinia-naïve patients may be enrolled to any cohort
  • There must be no history of allergy or untoward reaction to prior vaccination with vaccinia virus, for patients on cohorts 4, 5, 6, or 7
  • Patients for all cohorts should have no evidence of immunocompromise or autoimmunity as defined by:
  • HIV negative by serologic testing; this requirement is due to the potential for an unacceptable high risk of systemic viremia, if live virus vaccine were to be administered to an immunocompromised individual; while similar constructs have been given to HIV positive patients, concern is high for toxicity, particularly with vaccinia
  • No other diagnosis (past or present) of:
  • Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds; this requirement is due to a potential unacceptable high risk of systemic viremia, if study vaccine were to be administered to an immunocompromised individual
  • Any autoimmune disease such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome active Grave's disease; this requirement is due to the potential risks of autoimmunity
  • No prior radiation to > 50% of all nodal groups
  • No concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use
  • Patients must have recovered from the reversible side effects of prior therapy
  • Patients must be willing and able to travel to Georgetown University Hospital for treatment and follow-up during therapy and at least monthly thereafter until there is evidence of disease progression
  • Patients must be able to avoid close household contact (close household contacts are those who share housing or have close physical contact) with persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection

Who cannot join

  • Recent major surgery (within 21 days)
  • Frequent vomiting or severe anorexia
  • Pregnant or lactating women; this requirement is due to an unacceptable high risk of CEA antibody transfer, which may be potentially harmful to the developing fetus or infant; (NOTE: women and men enrolled in the study are to practice an effective method of birth control for at least six months after their last treatment on protocol)
  • Serious intercurrent medical illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis
  • The following therapies are prohibited and may not be administered to patients being treated on this protocol: chemotherapy, hormonal therapy, biologic therapy, and immunotherapy
  • Patients must have recovered completely from any reversible toxicity associated with their most recent therapy; typically this is 3-4 weeks for patients who most recently received cytotoxic therapy except for the nitrosoureas and mitomycin C for which 6 weeks is needed for recovery
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  • Patients with clinically active brain metastasis, uncontrolled seizure disorders, encephalitis, or multiple sclerosis
  • Patients can not have any history (past or present) of allergy to eggs or egg products
  • Patients with history of receiving CEA-containing vaccines are excluded from enrollment into any of the 8 actual study cohorts; however, patients with metastatic disease who have progressed (as defined by objective response criteria for solid measurable tumor; tumor marker elevation alone is not sufficient) on a CEA-containing vaccine, may be enrolled to this study as they arise if they meet the patient eligibility criteria, but will be added-in outside of the eight established cohorts, at the currently established safe dose level; additionally, these patients will receive only the rF-CEA(6D)-TRICOM vaccine (possibly along with GM-CSF if cohort 7 is the currently established safe dose level), but otherwise will be treated according to the protocol as any other patient on study; such additional patients will not count toward study accrual, determination of primary immunologic endpoints, or the determination of the MTD

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Lombardi Comprehensive Cancer Center at Georgetown University

    Washington D.C., District of Columbia, 20057

Other trials in United States

About this study

Official title: A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM (B7.1/ICAM/LFA-3) Alone, and in Combination With Vaccinia-CEA(6D)-TRICOM, and the Role of GM-CSF, in Patients With CEA Expressing Carcinomas

Phase I trial to compare the effectiveness of vaccine therapy with or without sargramostim in treating patients who have solid tumors. Vaccines may make the body build an immune response to kill tumor cells. Combining colony-stimulating factors such as sargramostim with vaccines may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose and toxicity profile of the novel CEA-based vaccine, rF-CEA(6D)-TRICOM (recombinant fowlpox-CEA(6D)-B7.1/ICAM-1/LFA-3), either alone or in combination with a second vaccine, rV-CEA(6D)-TRICOM (recombinant vaccinia-CEA(6D)-B7.1/ICAM-1/LFA-3) in patients with advanced CEA-bearing cancers.

II. To determine the maximum tolerated dose and toxicity profile of the novel CEA-based vaccine rV-CEA(6D)-TRICOM when given in combination with the maximum tolerated dose of rF-CEA(6D)-TRICOM, in patients with advanced CEA-bearing cancers.

III. To determine the safety and impact of colony stimulating factors (GM-CSF) on the immunologic response, when given in conjunction with the combination of rV-CEA(6D)-TRICOM (MTD) and rF-CEA(6D)-TRICOM (MTD) vaccines, in patients with advanced CEA-bearing cancers.

IV. To determine the change in CAP-1 directed T cells in patients treated with these vaccines using ELISPOT assay analysis.

  1. To perform a pilot analysis of the impact of vaccine therapy on the quantity of circulating CEA-positive cells in the patients treated on this study in order to develop and eventually validate a practical, intermediate bio-marker for the immunologic response to the vaccines.

VI. To document any objective anti-tumor responses that occur.

OUTLINE: This is a dose-escalation study of fowlpox-CEA-TRICOM (fCEA-TRI) vaccine and vaccinia-CEA-TRICOM (vCEA-TRI) vaccine.

STAGE I: Patients receive fCEA-TRI vaccine subcutaneously (SC) once daily on days 1, 29, 57, and 85.

Cohorts of 3-10 patients receive escalating doses of the fCEA-TRI vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity (DLT).

STAGE II: Patients receive vCEA-TRI vaccine intradermally once on day 1 and fCEA-TRI vaccine SC at the MTD determined in stage I once daily on days 29, 57, and 85.

Cohorts of 3-10 patients receive escalating doses of the vCEA-TRI vaccine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT.

STAGE III: A single cohort of 6-10 patients receive both vaccines as in stage II, at the MTDs determined in stages I and II, and sargramostim (GM-CSF) SC once daily on days 1-4, 29-32, 57-60, and 85-88.

Patients in any stage of the study with responding disease may receive additional doses of the fCEA-TRI vaccine monthly for 2 months and then every 3 months thereafter. Patients who have objective evidence of response (including mixed response) and/or a fall in an elevated serum CEA level after the sixth vaccine and who subsequently develop disease progression while on the extended every 3-month treatment schedule and have no other potentially better treatment alternatives available may continue treatment as per the monthly vaccination schedule for 2 additional months. Patients with stable or responding disease after those two monthly vaccines may continue monthly vaccines at the discretion of the principal investigator.

Patients are followed at 4 weeks and then monthly for 3 months.

Being tested
recombinant fowlpox-CEA(6D)/TRICOM vaccine, recombinant vaccinia-CEA(6D)-TRICOM vaccine, sargramostim, laboratory biomarker analysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • recombinant fowlpox-CEA(6D)/TRICOM vaccineBiological

    Also called fowlpox-CEA-B7-1/ICAM-1/LFA-3, rF-CEA(6D)TRICOM

    Given SC

  • recombinant vaccinia-CEA(6D)-TRICOM vaccineBiological

    Also called rV-CEA(6D)-TRICOM

    Given intradermally

  • sargramostimBiological

    Also called GM-CSF, Leukine, Prokine

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00009958
Study groupRoleWhat they receive
Stage IExperimentalPatients receive fCEA-TRI vaccine SC once daily on days 1, 29, 57, and 85.
Receives: Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine; Other: laboratory biomarker analysis
Stage IIExperimentalPatients receive vCEA-TRI vaccine intradermally once on day 1 and fCEA-TRI vaccine SC at the MTD determined in stage I once daily on days 29, 57, and 85.
Receives: Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine; Biological: recombinant vaccinia-CEA(6D)-TRICOM vaccine; Other: laboratory biomarker analysis
Stage IIIExperimentalA single cohort of 6-10 patients receive both vaccines as in stage II, at the MTDs determined in stages I and II, and sargramostim (GM-CSF) SC once daily on days 1-4, 29-32, 57-60, and 85-88.
Receives: Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine; Biological: recombinant vaccinia-CEA(6D)-TRICOM vaccine; Biological: sargramostim; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Immunologic response, measured by the frequency of interferon gamma-releasing T cells specific to CAP-1, an HLA-A2 restricted epitope of CEA, as measured by the ELISPOT assay

    Pre and post-vaccination CTL precursor frequencies will be calculated so that changes in CTL precursor frequencies can be compared between dose levels of the vaccine. Also, 95% confidence intervals can be calculated for the percent increases (or decreases) in CTL precursor frequencies between dose levels.

    Measured: Up to 3 months after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2004 (estimated)
  2. Study startNov 2000
  3. Primary completionApr 2010

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00009958
Sponsor's protocol ID
NCI-2012-03151
Other IDs
IBC20-09, P30CA051008, NCI-833, NIH/OBA-0006-405, CDR0000068427, GUMC-IBC20-09, GUMC-00101
Status last verified
May 2013
First submitted
2 Feb 2001
Last updated
16 May 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing recombinant fowlpox-CEA(6D)/TRICOM vaccine, recombinant vaccinia-CEA(6D)-TRICOM vaccine and sargramostim in people with Unspecified Adult Solid Tumor, Protocol Specific, 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 25 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 16 May 2013. 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 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. 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?

Immunologic response, measured by the frequency of interferon gamma-releasing T cells specific to CAP-1, an HLA-A2 restricted epitope of CEA, as measured by the ELISPOT assay (time frame: Up to 3 months after completion of study treatment). 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 NCT00009958.

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 16 May 2013.

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