To Immunize Patients With Extensive Stage SCLC Combined With Chemo With or Without All Trans Retinoic Acid

NCT00617409 | Completed Phase 2 Results DMC

• 4 other identifiers: MCC-152061057900147NE0705-857
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to test a tumor (cancer) vaccine given along with chemotherapy to determine if this vaccine will increase the chances of the tumor shrinking and/or the amount of time that people who have this disease will live.

Conditions

Small Cell Lung Cancer

Keywords

SCLC; vaccine; immunize

Outcome Measures

Primary Outcomes (1)

• Tumor Response Rate (RR)

  Overall Response: Complete Response (CR) + Partial Response (PR) + Stable Disease (SD). Efficacy of second line chemotherapy (single agent paclitaxel) after progression following the dendritic cell(DC)-based p53 vaccine (Ad.p53-DC vaccine), with (Arm C). To estimate the objective tumor response rate for each treatment group. Tumor response to be assessed via radiographic imaging after every 2 cycles of chemotherapy (paclitaxel). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started. PD: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  12 months

Secondary Outcomes (1)

• Overall Survival (OS)

  Up to 24 months

Study Arms (3)

Standard of Care

ACTIVE COMPARATOR

Arm A - Active Comparator: Observation (Standard of Care) + Second Line Chemotherapy

Drug: Paclitaxel

Ad.p53-DC Vaccines

EXPERIMENTAL

Arm B - Experimental: Ad.p53-DC vaccines + Second Line Chemotherapy

Drug: Paclitaxel; Biological: Drug: Ad.p53-DC vaccines

Ad.p53-DC Vaccines + ATRA

EXPERIMENTAL

Arm C - Experimental: Ad.p53-DC vaccines + All -trans Retinoic Acid (ATRA) + Second Line Chemotherapy

Drug: Paclitaxel; Biological: Drug: Ad.p53-DC vaccines; Drug: All -trans Retinoic Acid (ATRA)

Interventions

Paclitaxel DRUG

All groups wil receive paclitaxel as second line chemotherapy if their cancer spreads. At any point when a patient develops evidence of progressive disease, the patient will be treated with second-line chemotherapy. Paclitaxel will be given at a dose of 200 mg/m² on day 1 of 21 day cycles.

Also known as: Antitumor agent, Chemotherapy

Ad.p53-DC Vaccines; Ad.p53-DC Vaccines + ATRA; Standard of Care

Drug: Ad.p53-DC vaccines BIOLOGICAL

Patients randomized to Arm B will receive vaccinations on 3 occasions, at 2 week intervals. 1-5x106 p53 positive DCs in 1 ml will be injected intradermally into 4 separate sites (0.25 ml injected at each site), in bilateral proximal upper and lower extremities (in the regions of the axillary and inguinal nodal basins). Patients will be restaged approximately 2-3 weeks after vaccine # 3 (first vaccine course). If patients show no sign of disease progression at restaging, then a second leukopheresis will be performed. Patients will then be vaccinated 3 more times (second vaccine course) at 4-week intervals, for a total of 6 possible vaccines. Restaging will occur 2-4 weeks after completing the second vaccine course. Patients in Arm C will receive vaccines at the same dose and schedule as described for patients in Arm B. In addition, they will receive 150 mg/m² of ATRA for 3 days prior to each vaccine administration (followed by vaccine administration on the fourth day).

Also known as: INGN 225

Ad.p53-DC Vaccines; Ad.p53-DC Vaccines + ATRA

All -trans Retinoic Acid (ATRA) DRUG

The patients in Arm C will receive vaccines at the same dose and schedule as described for patients in Arm B. In addition, they will receive 150 mg/m² of ATRA for 3 days prior to each vaccine administration (followed by vaccine administration on the fourth day).

Also known as: tretinoin, Vesanoid, INGN 225

Ad.p53-DC Vaccines + ATRA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Paclitaxel; Antineoplastic Agents; Drug Therapy; INGN 225; Tretinoin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Pigments, Biological; Biological Factors

Limitations and Caveats

Protocol V.10.1, 04/11/2012: Arm A was closed due to lack of feasibility; Arm B was closed at the end of the first stage due to lack of efficacy.

Results Point of Contact

• Title: Dr. Scott Antonia
• Organization: H. Lee Moffitt Cancer Center and Research Institute

scott.antonia@moffitt.org

813-745-3883

Study Officials

• Scott Antonia, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2008
• First Posted: February 18, 2008
• Study Start: October 2, 2007
• Primary Completion: September 21, 2015
• Study Completion: January 31, 2019
• Last Updated: November 8, 2019
• Results First Posted: November 1, 2016

Record last verified: 2019-11

Locations

US (1)