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A Randomized Phase II Trial Using Dendritic Cells Transduced With an Adenoviral Vector Containing the p53 Gene to Immunize Patients With Extensive Stage Small Cell Lung Cancer in Combination With Chemotherapy With or Without All Trans Retinoic Acid


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Small Cell Lung Cancer

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Trial Information

A Randomized Phase II Trial Using Dendritic Cells Transduced With an Adenoviral Vector Containing the p53 Gene to Immunize Patients With Extensive Stage Small Cell Lung Cancer in Combination With Chemotherapy With or Without All Trans Retinoic Acid


After initial diagnosis patients will be treated with a standard platinum/etoposide regimen.
This standard first-line chemotherapy may/will be administered to patients under the
direction of their primary medical oncologist inside or outside of the Moffitt Cancer
Center. Patients will receive the platinum drug on day 1 and etoposide on days 1-3 of each
21-day cycle for 4-6 cycles. Patients who have progressive disease at this point are changed
to second line chemotherapy, and will not be eligible to participate in this clinical trial.
Patients who achieve a complete response, partial response, or stable disease (CR, PR, or
SD) after standard first-line chemotherapy will be enrolled. Radiographic studies and tumor
measurements are repeated 3-6 weeks after the last dose of chemotherapy (+/- PCI) and may be
repeated after prophylactic cranial irradiation (PCI) at the discretion of the principal
investigator (PI) and treating physician.

PCI will be permitted at the discretion of the treating oncologist(s). The initial
radiation consultation and simulation should occur as soon as the final staging has
occurred. Ideally, treatment should commence 1-2 weeks after final staging has been
confirmed and will be administered in 10-15 fractions over a 2-3 week period, as recommended
by the treating radiation oncologist. Although steroid use is not prohibited, it is
recommended and preferred that they not be used during PCI (steroids will have to be
discontinued ≥ 2 weeks before first vaccination). PCI can also be considered between
vaccines #4 and #5 or vaccine #5 and #6 in those patients eligible for the second course of
vaccinations. Systemic dose of steroids will NOT be allowed in these cases unless strictly
necessary and after discussion with the PI.

Patients who achieve CR, PR or SD after the completion of first line chemotherapy +/- PCI
will be screened for initial registration. Screening tests and procedures will be performed
approximately 4-6 weeks after the completion of first line chemotherapy or 6-9 weeks after
completion of PCI. Ideally, screening should be completed 1-2 weeks prior to leukopheresis.

Patients who successfully complete the screening exams for initial registration will be
randomized into one of three study arms.

Inclusion Criteria


Inclusion Criteria at the time of initial registration:

- Patients must have a histological confirmed diagnosis of Small Cell Lung Cancer
(SCLC)

- Must have extensive stage SCLC

- Must have completed first line chemotherapy: 4-6 cycles of a standard
platinum/etoposide regimen and PCI if chosen at the discretion of the treating
Oncologist

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- Acceptable (adequate) organ function including:

- White blood count (WBC) >2,500/mm³ and Absolute neutrophil count (ANC)
>1,200/mm³

- Platelets > 75,000/mm³

- Hematocrit > 24% OR Hemoglobin ≥8.5g/dl

- Bilirubin < 2.0 mg/dl

- Creatinine < 2.0 mg/dl

- Aspartic transaminase (AST/SGOT) ≤2 x upper limit of normal (ULN)

- Alkaline phosphatase ≤3 x ULN

- Patients must have achieved responsive or non-progressive disease status (stable
disease [SD], partial response [PR], or complete response [CR]) assessed 4-6 weeks
after the last cycle of first line chemotherapy. SD, PR or CR may be confirmed after
completion of prophylactic cranial irradiation (PCI) at the discretion of the
principal investigator (PI) after discussion with the treating oncologist.

- Males and Females of reproductive potential must agree to use effective contraception
during the study and for at least 4 weeks after the last dose of ATRA. Patients are
instructed and agree to notify the principal investigator should a pregnancy occur
for themselves or their partner.

- Willing and able to sign written informed consent and be able to comply with the
study protocol for the duration of the study

Exclusion Criteria at the time of initial registration:

- Patients with severe, uncontrolled intercurrent illness or infection

- Anticipated requirement for systemic chronic steroid use at the time of vaccination,
unless specifically indicated for dose supplementation or replacement of established
corticosteroid insufficiency

- Receiving systemic doses of corticosteroids should have them discontinued ≥ 2 weeks
prior to starting vaccination (this include patients receiving steroids with PCI).
Inhaled steroids should also be discontinued if at all possible. Chronic, stable
doses of inhaled steroids for the treatment of chronic obstructive pulmonary disease
(COPD), etc. are allowed if in the opinion of the treating physician(s) they cannot
be stopped.

- Any pre-existing immunodeficiency condition, or a known history of human
immunodeficiency virus (HIV), Hepatitis B or Hepatitis C

- Uncontrolled and/or symptomatic central nervous system (CNS) metastasis

- Pregnant or lactating women. A pregnancy test-serum Beta human chorionic gonadotropin
(bHCG) will be obtained during the screening process.

- Have received any chemotherapy other than the first line chemotherapy specified in
the study protocol: standard platinum/etoposide regimen

- Have received any prior investigational drugs including immunotherapy, gene therapy,
hormone therapy, biologic therapy for treatment of SCLC

- Any known pre-existing autoimmune disorder

- History of a second malignancy within the previous 3 years. Exceptions include:
non-melanoma skin cancers, any in-situ carcinomas and successfully treated early
stage malignancies without evidence of recurrence for > 18 months.

- Have not recovered from any chemotherapy-related or other therapy-related toxicity at
study entry

- Have had major surgery without full recovery or major surgery within 3 weeks of the
start of vaccine treatment

- Patients with other significant diseases or disorders that, in the Investigator's
opinion, would exclude them from the study

Pre-Pheresis Criteria:

- Patients must have had a successful harvest of peripheral blood mononuclear cell
(PBMC) with leukopheresis at least 6-10 weeks after chemotherapy.

- ECOG performance status of 0-2

- The last dose of first line chemotherapy must have been administered at least 4 weeks
prior to the first vaccine administration.

- Patients who received radiation therapy: last dose of radiation must have been
completed at least 2 weeks prior to the first vaccine administration and the patient
must have recovered from the toxic effects of the treatment prior to study enrollment
(except for alopecia)

- Patients who received steroid therapy: last steroid dose must have been given at
least 2 weeks prior to the first vaccine administration

- Adequate organ function:

- WBC > 2,500/mm³ and ANC >1,200/mm³

- Platelets > 75,000/mm³

- Hematocrit > 25%

- Hemoglobin ≥9g/dl

- Bilirubin < 2.0 mg/dl

- Creatinine < 2.0 mg/dL

- AST/SGOT ≤ 2 x ULN

- Alkaline phosphatase < 3 x ULN

- Patients must have signed informed consent at initial registration.

- HLA-A*0201 Testing as determined by flow cytometry followed by molecular analysis of
a peripheral blood specimen, however this result will not be an inclusion criterion

Pre-Paclitaxel Eligibility:

- Progressive disease after observation (Arm A) or vaccinations (Arms B and C)

- ECOG performance status of 0-2

- Adequate organ function:

- WBC > 2,500/mm³ and ANC >1,200/mm³

- Platelets > 75,000/mm³

- Hematocrit > 25%

- Hemoglobin ≥9g/dl

- Bilirubin < 2.0 mg/dl

- Creatinine < 2.0 mg/dL

- AST/SGOT ≤ 2 x ULN

- Alkaline phosphatase < 3 x ULN

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Tumor Response in Each Group

Outcome Description:

To evaluate the efficacy of second line chemotherapy (single agent paclitaxel) after progression following the dendritic cell-based p53 vaccine (Ad.p53-DC vaccine), with (Arm C. That is, to estimate the objective tumor response rate for each treatment group. Tumor response will be assessed via radiographic imaging which will occur after every 2 cycles of chemotherapy (paclitaxel). Tumor response will be defined as partial response (PR) or complete response (CR).

Outcome Time Frame:

24 months

Safety Issue:

No

Principal Investigator

Scott Antonia, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

MCC-15206

NCT ID:

NCT00617409

Start Date:

October 2007

Completion Date:

June 2014

Related Keywords:

  • Small Cell Lung Cancer
  • SCLC
  • vaccine
  • immunize
  • Lung Neoplasms
  • Small Cell Lung Carcinoma

Name

Location

H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612