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Non-Small Cell Lung CancerPhase 1NCT01799161

Combination of gp96-Ig Vaccine, Theophylline and Oxygen for the Treatment of Patients With Advanced, Relapsed or Metastatic Non-Small Cell Lung Cancer

A Phase 1 study testing gp96-Ig Vaccine, Theophylline and Oxygen in people with Non-Small Cell Lung Cancer and Non-small-cell Lung Carcinoma, run by Eckhard Podack.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

NSCLC tumors are appropriate targets for active immunotherapy, because they are non-immunogenic, which indicates that NSCLC does not stimulate a spontaneous immune response. NSCLC tumor-secreted gp96-Ig is an ideal vaccine because it combines adjuvant activity with polyvalent peptide specificity. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
gp96-Ig Vaccine, Theophylline and Oxygen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2014to Apr 2018
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

  • Histologically confirmed NSCLC (squamous, adeno-, large cell anaplastic, bronchoalveolar, and non-small cell carcinoma NOS): stage IIIB with malignant pleural effusion, stage IV, or recurrent disease.
  • At least one site of measurable disease.
  • Brain metastasis if present and treated must be stable by CT scan or MRI for at least 4 weeks after treatment.
  • Patient must have received and failed at least one line of palliative therapy (chemotherapy or biological therapy)
  • Age >= 18 years.
  • ECOG performance status 0-2.
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  • Life expectancy >= 3 months.
  • Laboratory parameters
  • Hemoglobin levels >= 10.0 (transfusions allowed if necessary).
  • ANC >= 1,500.
  • Platelets >= 100k.
  • Creatinine clearance >= 50 ml/min.
  • Total and direct bilirubin: < 3.0 x upper institution limit for normal.
  • Liver function tests: AST, ALT, and AlkP < 3.0 x upper institution limit for normal.
  • Signed informed consent.

Who cannot join

  • Active or symptomatic cardiac disease such as congestive heart failure, angina pectoris or recent myocardial infarction. Patients with history of these conditions who are stable taking cardiac medications will also be excluded.
  • Pregnant or lactating women (negative test for pregnancy is required of women of childbearing potential).
  • Known HIV infection.
  • Uncontrolled or untreated brain or spinal cord metastases.
  • Active infection.
  • Concomitant steroid or other immunosuppressive therapy.
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  • Other active malignancies present within the past three years, except for basal and/or squamous cell carcinoma(s) or in situ cervical cancer.
  • Meningeal carcinomatosis.
  • Chemotherapy, radiation therapy, or other anti-tumor therapy during the last three weeks.
  • Immune deficiency syndromes, including the following: rheumatoid arthritis, systemic lupus erythematousus, Sjogren's disease, sarcoidosis, vasculitis, polymyositis, glomerulonephritis.
  • Compromised lung function:
  • FeV1 < 30% of the predicted value, or
  • DLCO < 30% of the predicted value, or
  • PCO2 > 45 mmHg.

About this study

Official title: Phase 1 Study of the Combination of gp96-Ig Cell Based Lung Cancer Vaccine With Suppression of Adenosinergic Pathways With Theophylline and Oxygen for the Treatment of Non-Small Cell Lung Cancer (NSCLC) Patients With Advanced (Stage IIIB), Relapsed or Metastatic (Stage IV) Disease Who Have Failed Palliative Therapy.

NSCLC tumors are appropriate targets for active immunotherapy, because they are non-immunogenic, which indicates that NSCLC does not stimulate a spontaneous immune response.

NSCLC tumor-secreted gp96-Ig is an ideal vaccine because it combines adjuvant activity with polyvalent peptide specificity. Tumor secreted gp96 activates dendritic cells (DC), natural killer cells (NK) and cytotoxic T lymphocytes (CTL). Tumor cells can be killed by NK-specific mechanisms, by promiscuous killing of CD8 CTL through NKG2D, and by MHC restricted CD8 CTL activity. The activation of DC and NK by tumor secreted gp96 may also counteract the generation of immuno-suppressive CD4 regulatory cells.

Read more

Suppression of adenosinergic pathways by oxygen and theophylline in combination with immunotherapy will improve tumor rejection.

Allogeneic, gp96-Ig secreting tumor cells used as vaccine are expected to generate NK and CTL with activity to the patient's autologous tumor.

Read the detailed description

This is a proof of principle trial investigating a heat shock protein gp96 Ig-secreting, allogeneic tumor cell-vaccine (gp96-Ig vaccine) administered in combination with suppression of adenosinergic pathways by oxygen and Theophylline to patients with non-small cell lung cancer (NSCLC). Allogeneic, cultured lung adenocarcinoma cells transfected with HLA A1 and gp96-Ig will be irradiated and injected intradermally into patients suffering from advanced, relapsed, or metastatic NSCLC. HLA matching is not required. Safety and immunogenicity of the combined treatment will be studied in three patient cohorts that will receive twice monthly, weekly or twice weekly vaccination plus Theophylline and oxygen.

Immune response to vaccination of patients will be measured by determining adenocarcinoma-specific CD8 CTL precursor frequencies. ELI-spot assay for interferon-y (IFN-y) will be done to measure cytotoxic function of CD8 cells challenged in vitro with vaccine cells or autologous tumor cells. Multiparameter flow cytometry of CD8 and CD4 cells will be carried out to assess functional characteristics and to assess adenosine receptor levels and expression of hypoxia inducible factor-1alpha.

Patients will be randomized in equal allocation (1:1:1) to one of three dose-schedule (DS) cohorts defined by the frequency of vaccination. All patients will receive a total course dose of gp96 vaccine. A total of 36 patients, 12 per DS cohort, will be enrolled. We expect to accrue at a rate of two patients per month except at the onset of study when successive enrollment will be spaced to allow observation of first course toxicity in the first several patients. (See Section 3.3.4 for details.) Patients will be followed for a minimum of one year, thus study duration is expected to be three years.

Being tested
gp96-Ig Vaccine, Theophylline, Oxygen, Immunologic Evaluation
Keywords
NSCLC, Lung Cancer, gp96, gp96 Vaccine, AD100-gp96Ig-HLA A1
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

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

  • gp96-Ig VaccineBiological

    Also called gp96, AD100-A1-gp96Ig vaccine, Short gp96 Vaccine, gp96IG and HLA A1 Transfected NSCLC Cell Line

  • TheophyllineDrug

    Also called dimethylxanthine

    300 mg capsule daily of Theophylline during 1st course, then adjusted dose

  • OxygenOther

    Also called O2

    24-hr oxygen delivered via nasal cannula or oxygen mask during 1st course, then adjusted dose.

  • Immunologic EvaluationProcedure or surgery

    Also called Peripheral Blood Sample, Tumor Sample

    Frequency of IFN-y,CD8 cells in response to vaccine in available tumor samples Blood draw to assess immunological response [frequency of CD4+, FoxP3 (Treg), et al] in treated patients.

Study groups in NCT01799161
Study groupRoleWhat they receive
DS-1Active comparator6 week course of gp96 Vaccine: >= 4 x 10^7 cells twice monthly on Day 1. Up to 3 courses, 9 vaccinations.
Receives: Biological: gp96-Ig Vaccine; Drug: Theophylline; Other: Oxygen; Procedure: Immunologic Evaluation
DS-2Active comparator6 week course of gp96 Vaccine: >= 2 x 10^7 cells weekly on Day 1. Up to 3 courses, 18 vaccinations.
Receives: Biological: gp96-Ig Vaccine; Drug: Theophylline; Other: Oxygen; Procedure: Immunologic Evaluation
DS-3Active comparator6 week course of gp96 Vaccine: >= 1 x 10^7 cells twice weekly on Days 1 and 4. Up to 3 courses, 36 vaccinations.
Receives: Biological: gp96-Ig Vaccine; Drug: Theophylline; Other: Oxygen; Procedure: Immunologic Evaluation

What is being measured

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

  1. Number of Adverse Events Experienced by Patients Receiving Study Treatment

    Evaluation of the safety of administering a heat shock protein gp96-Ig-secreting allogeneic tumor cell-vaccine (gp96-Ig vaccine) in combination with oxygen and theophylline in patients with advanced NSCLC.

    Measured: 36 months

Secondary outcomes (3)

  1. Immune response to vaccination

    Measured: 36 months

  2. Clinical Response to gp96-Ig Vaccination

    Clinical Response to gp96-Ig Vaccination measured by CT scan and RECIST criteria v 1.1.

    Measured: 36 months

  3. Recommended Dose-schedule Combination for further testing

    The recommended Dose-schedule combination of gp96-Ig vaccine, Theophylline and Oxygen for NSCLC in further testing

    Measured: 36 Months

Timeline

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

  1. First posted26 Feb 2013 (estimated)
  2. Study startDec 2014
  3. Primary completionApr 2018 (estimated)

Why it stopped: Insufficient funding

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01799161
Sponsor's protocol ID
20110847
Status last verified
Nov 2014
First submitted
22 Feb 2013
Last updated
17 Nov 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing gp96-Ig Vaccine, Theophylline and Oxygen in people with Non-Small Cell Lung Cancer and Non-small-cell Lung Carcinoma, run by Eckhard Podack.

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 15 inclusion and 14 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: withdrawn, as of the sponsor's last update on 17 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

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 withdrawn before enrolling participants, so there are no results.

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 Adverse Events Experienced by Patients Receiving Study Treatment (time frame: 36 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 NCT01799161.

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 17 Nov 2014.

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