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Colorectal CancerPhase 1/2CEA(6D)VRPNCT00529984

A Phase I/II Study With CEA(6D) VRP Vaccine in Patients With Advanced or Metastatic CEA-Expressing Malignancies

A Phase 1/2 study testing AVX701 in people with Colorectal Cancer and Breast Cancer, run by AlphaVax, Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

STUDY OBJECTIVES 1. The primary objective of this protocol is to determine the safety of immunization with CEA(6D) VRP in patients with advanced or metastatic CEA expressing malignancies. 2. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer, Breast Cancer, Lung Cancer
What is being tested?
AVX701
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
Sep 2007to May 2010
Phase
Phase 1/2
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cohorts 1-4 only:
  • Histologically confirmed diagnosis of metastatic malignancy due to a tumor expressing CEA.
  • The tumor must express CEA as defined by immunohistochemical staining, CEA blood level, or a tumor known to be universally CEA positive.
  • Must have received treatment with standard therapy having a possible overall survival benefit or refused such therapy.
  • Must have received and progressed through at least one line of palliative chemotherapy for colorectal, breast, lung, or pancreatic cancer. For other malignancies, if a first line therapy with survival or palliative benefit exists, it should have been administered and there should have been progressive disease.
  • Cohort 5 Only:
Show all 19Show fewer
  • Histologically confirmed colon cancer (rectal cancer excluded). Since colon cancer is nearly universally CEA positive, CEA staining is not required.
  • Documented stage III colon cancer with no evidence of disease.
  • One to six months following standard post-operative adjuvant treatment, which should have consisted of 5-fluorouracil and folinic acid or capecitabine with or without oxaliplatin for 4-6 months)
  • All Cohorts:
  • Karnofsky performance status ≥ 70%.
  • Estimated life expectancy > 6 months and not expected to require further systemic chemotherapy for at least 3 months.
  • Age ≥ 18 years.
  • Adequate hematologic function (WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL, and platelets ≥ 100,000/microliter).
  • Adequate renal and hepatic function, (serum creatinine < 1.5 mg/dL, bilirubin ≤ 1.5 mg/dL, and ALT and AST ≤ 2.5 x upper limit of normal).
  • Patients who have received CEA-targeted immunotherapy, if treatment was discontinued at least 3 months before enrollment.
  • Patients who are taking medications that do not have a known history of immunosuppression are eligible for this trial.
  • Ability to understand and provide signed informed consent.
  • Ability to return to Duke University Medical Center for adequate follow-up, as required by protocol.

Who cannot join

  • Concurrent cytotoxic chemotherapy or radiation therapy (must be at least 3 months between any prior CEA-targeted immunotherapy and study treatment and at least 4 weeks between any other prior therapy and study treatment).
  • Patients with previously resected brain metastases will be permitted if a CT or MRI scan shows no metastasis within 1 month before enrollment.
  • History of autoimmune disease.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: A Phase I/II Study of Active Immunotherapy With CEA(6D)VRP Vaccine(AVX701)in Patients With Advanced or Metastatic Malignancies Expressing CEA or Stage III Colon Cancer

STUDY OBJECTIVES

  1. The primary objective of this protocol is to determine the safety of immunization with CEA(6D) VRP in patients with advanced or metastatic CEA expressing malignancies.
  2. The secondary objectives are to evaluate CEA-specific immune response to the immunizations and obtain preliminary data on response rate.
Read the detailed description

CEA represents an attractive target antigen for immunotherapy since it is over expressed in nearly all colorectal cancers and pancreatic cancers, and is also expressed by some lung and breast cancers, and uncommon tumors such as medullary thyroid cancer, but is not expressed in other cells of the body except for low-level expression in gastrointestinal epithelium [1]. That CEA is a potential target for T cell mediated immune responses in humans is demonstrated by the observation that CEA contains epitopes that may be recognized in an MHC restricted fashion by T cells [2-11]. Specifically, there is support for the existence of human cytolytic T cells (CTLs) that recognize CEA epitopes that bind to MHC molecules HLA- A2, A3, and A24. For the most part, these T cells have been generated by in vitro cultures using antigen-presenting cells pulsed with the epitope of interest to stimulate peripheral blood mononuclear cells. In addition, T cell lines have been generated after stimulation with CEA latex beads, CEA protein-pulsed plastic adherent peripheral blood mononuclear cells, or DCs sensitized with CEA RNA. T cells have also been generated from patients immunized with a vaccinia vector encoding CEA immunogen (discussed below). Using high-performance liquid chromatography mass-spectrometry-based approaches, HLA A2-presented peptides from CEA have been identified in primary gastrointestinal tumors [12]. Of the HLA A2 restricted epitopes of CEA, CAP-1, a nine amino acid sequence, has been shown to stimulate CTLs from cancer patients immunized with vaccinia-CEA. Cap-1(6D) is a peptide analog of CAP-1. Its sequence includes a heteroclitic (nonanchor position) mutation, resulting in an amino acid change from Asn to Asp, to enhance recognition by the T-cell receptor without any change in binding to HLA A2. Compared with the non mutated CAP-1 epitope, Cap-1(6D) has been shown to enhance the sensitization of CTLs by 100 to 1,000 times [3, 5, 13]. CTL lines could be elicited from peripheral blood mononuclear cells of healthy volunteers by in vitro sensitization to the Cap-1(6D) peptide but not to the CAP-1 peptide. These cell lines can lyse human tumor cells expressing endogenous CEA.

Being tested
AVX701
Keywords
CEA, CEA-expressing malignancies, Metastatic malignancies, VRP Vaccine, Alphavirus replicons, Molecular therapeutics, Stage III colon cancer
Medical subject headings
Colorectal Neoplasms, Breast Neoplasms, Lung Neoplasms, Pancreatic Neoplasms, Colonic Neoplasms, Neoplasms

What participants receive

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

  • AVX701Biological

    4 doses of AVX701 at 4e7 IU given at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease

  • AVX701Biological

    4 doses of AVX701 at 1e8 IU given at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease

  • AVX701Biological

    4 doses of AVX701 at 4e8 IU given at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease

  • AVX701Biological

    4 doses of AVX701 given at the maximally tolerated dose at T=0, 3, 6, 9 weeks. Option for subjects to receive additional immunizations every 3 months after the 4th immunization if no dose-limiting toxicities or is without progressive disease

  • AVX701Biological

    4 Doses of AVX701 given to Stage III colon cancer subjects at the maximally tolerated dose at T=0, 3, 6, 9 weeks. There will be no option for subjects to receive additional immunizations.

Study groups in NCT00529984
Study groupRoleWhat they receive
Cohort 1ExperimentalNot described
Receives: Biological: AVX701
Cohort 2ExperimentalNot described
Receives: Biological: AVX701
Cohort 3ExperimentalNot described
Receives: Biological: AVX701
Cohort 4ExperimentalNot described
Receives: Biological: AVX701
Cohort 5ExperimentalNot described
Receives: Biological: AVX701

What is being measured

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

  1. determine the safety of immunization with CEA(6D) VRP

    Measured: 2.5 years

Secondary outcomes (1)

  1. evaluate CEA-specific immune response to immunizations

    Measured: 3 years

Timeline

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

  1. First posted14 Sep 2007 (estimated)
  2. Study startSep 2007
  3. Primary completionMay 2010
  4. Study completionMay 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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00529984
Sponsor's protocol ID
AVX701
Other IDs
P01CA078673-04
Acronym
CEA(6D)VRP
Status last verified
Jul 2012
First submitted
12 Sep 2007
Last updated
12 Jul 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AVX701 in people with Colorectal Cancer and Breast Cancer, run by AlphaVax, Inc. 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 19 inclusion and 3 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 12 Jul 2012. 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 combined 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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

determine the safety of immunization with CEA(6D) VRP (time frame: 2.5 years). 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 NCT00529984.

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 12 Jul 2012.

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