Combination Vaccine Immunotherapy (DRibbles) for Patients With Definitively-Treated Stage III Non-small Cell Lung Cancer

Tracking Information
First Submitted Date ICMJE	July 24, 2013
First Posted Date ICMJE	July 26, 2013
Last Update Posted Date	July 6, 2017
Study Start Date ICMJE	July 2013
Actual Primary Completion Date	November 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 24, 2013)	Identify the regimen that produces the strongest antibody response [ Time Frame: 95 days ]; The best regimen will be defined as the one that generates the greatest increase in the number of strong antibody responses as defined by a greater than 15-fold increase in antibody, as measured using the Immune Response Biomarker Profiling Array (Invitrogen) on the day 95 serum sample.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01909752 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 24, 2013)	Safety [ Time Frame: 43 weeks ]To evaluate the overall safety of allogeneic NSCLC DRibble vaccine alone or in combination with either imiquimod or GM-CSF, as adjuvant treatment for definitively-treated patients with Stage IIIA or B NSCLC. During the treatment period, patients will be seen in clinic 13 times over a 22-week period; performance status and side-effects will be evaluated at each visit.; Progression free survival [ Time Frame: 2 years ]Evaluate progression-free survival. Tumor measurements by CT scan will be obtained at week 16 and subsequently at the discretion of the treating investigator. After the treatment period, patients will be seen every 3 months for 2 years, or until progressive disease.; Immune response and progression-free survival correlation. [ Time Frame: 2 years ]Evaluate whether any immune response data correlate with progression-free survival. Immune response data will be collected 12 times over the first 43 weeks and then every 3 months until two years or progressive disease. This data will be correlated with progression-free survival.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Combination Vaccine Immunotherapy (DRibbles) for Patients With Definitively-Treated Stage III Non-small Cell Lung Cancer
Official Title ICMJE	Randomized Phase II Trial of Cyclophosphamide With Allogeneic Non-Small Cell Lung Cancer (NSCLC) DRibble Vaccine Alone or With Granulocyte-Macrophage Colony-Stimulating Factor or Imiquimod for Adjuvant Treatment of Definitively-Treated Stage IIIA or IIIB NSCLC
Brief Summary	This study will test an investigational vaccine, called DRibbles, for the treatment of non-small cell lung cancer (NSCLC). We hypothesize that vaccination with the DRibble vaccine will cause an immune responses against proteins contained in the DRibble vaccine and the protein antigens targeted by this strong immune response will include common antigens shared by both the vaccine and the patient's tumor.
Detailed Description	This is an open-label, randomized study in which the first 33 patients will be assigned to receive the either: DRibbles vaccine and HPV vaccine; DRibbles vaccine, HPV vaccine, and imiquimod; DRibbles vaccine, HPV vaccine, and GM-CSF After 11 patients have been assigned to each group, the study arm with the greatest number of vaccine-induced strong antibody responses will then continue with enrollment of 15 further patients. The primary objective is to determine the best strategy to induce strong (>15 fold) tumor-specific or tumor-associated antibody responses in patients with stage III A and B NSCLC. The goal is to select one regimen to advance to additional clinical trials.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Carcinoma, Non-Small-Cell Lung
Intervention ICMJE	Drug: Cyclophosphamide Cyclophosphamide (300 mg/m2) will be administered as a single dose three days prior to beginning vaccine therapy. Other Name: Cytoxin; Biological: DRibble vaccine DRibble vaccine will be administered at Weeks 1, 4, 7, 10, 13, 16, 19, 25, 31, 37, and 43.; Drug: Imiquimod Imiquimod cream (5%, 250 mg containing 12.5 mg imiquimod - one packet/day) will be self applied once per day starting with the second vaccine (week 4). Immediately following vaccination and for four days following each vaccine cycle (total 5 days) imiquimod will be applied to a 4 x 5-cm outlined area of healthy extremity skin that includes the vaccine site. Other Name: Aldara; Drug: GM-CSF GM-CSF will be administered at 50 mcg/day starting with the second vaccine (week 4) and continuing with each subsequent vaccine. A volume of 0.2 cc will be delivered by the CADD-MSTM 3 Ambulatory infusion pump at a rate of 0.008 cc/hr. The pump will be refilled after three days for a total of six days of infusion. Other Name: Leukine; Biological: HPV vaccine Immunization with HPV vaccine will consist of two 0.5-mL intramuscular injection at the time of the first and third vaccinations. The preferred site of administration is the deltoid region of the upper arm. Other Name: Ceravix
Study Arms	Experimental: DRibble Vaccine Alone Cyclophosphamide (300 mg/m2) will be administered as a single dose three days prior to beginning vaccine therapy. DRibble vaccine will be administered at Weeks 1, 4, 7, 10, 13, 16, 19, 25, 31, 37, and 43. Immunization with HPV vaccine intramuscular injection at the time of the first and third vaccinations. Interventions: Drug: Cyclophosphamide Biological: DRibble vaccine Biological: HPV vaccine; Experimental: DRibble vaccine with imiquimod Cyclophosphamide (300 mg/m2) will be administered as a single dose three days prior to beginning vaccine therapy. DRibble vaccine will be administered at Weeks 1, 4, 7, 10, 13, 16, 19, 25, 31, 37, and 43. Imiquimod cream (5%, 250 mg containing 12.5 mg imiquimod - one packet/day) will be self applied once per day starting with the second vaccine (week 4) and for four days following each vaccine cycle. Immunization with HPV vaccine intramuscular injection at the time of the first and third vaccinations. Interventions: Drug: Cyclophosphamide Biological: DRibble vaccine Drug: Imiquimod Biological: HPV vaccine; Experimental: DRibble vaccine with GM-CSF Cyclophosphamide (300 mg/m2) will be administered as a single dose three days prior to beginning vaccine therapy. DRibble vaccine will be administered at Weeks 1, 4, 7, 10, 13, 16, 19, 25, 31, 37, and 43. GM-CSF will be administered at 50 mcg/day starting with the second vaccine (week 4) and continuing with each subsequent vaccine. Immunization with HPV vaccine intramuscular injection at the time of the first and third vaccinations. Interventions: Drug: Cyclophosphamide Biological: DRibble vaccine Drug: GM-CSF Biological: HPV vaccine
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 3, 2017)	12
Original Estimated Enrollment ICMJE; (submitted: July 24, 2013)	48
Actual Study Completion Date	April 2017
Actual Primary Completion Date	November 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Stage IIIA or IIIB histologically proven non-small cell lung cancer; Completion of definitive therapy; Enrollment from 28 days to 12 weeks from completion of definitive therapy; Toxicities from definitive therapy resolved to less than grade 1; ECOG performance status 0-1; Negative pregnancy test in women of childbearing potential; Agree to avoid pregnancy or fathering a child while on study treatment; Ability to give informed consent and comply with protocol; Anticipated survival minimum of 6 months; Prior therapy with investigational agents must be completed at least 3 weeks prior to study enrollment; Normal organ and marrow function as defined by specific lab tests; Archived tumor tissue available Exclusion Criteria: Active autoimmune disease except for vitilogo or hypothyroidism; Active other malignancy; Known HIV+ and/or Hepatitis B or C positive; Medical or psychiatric conditions that would preclude safe participation; Ongoing chemotherapy
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01909752
Other Study ID Numbers ICMJE	UbiVac DPV-001; R44CA121612 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	UbiVac
Study Sponsor ICMJE	UbiVac
Collaborators ICMJE	National Cancer Institute (NCI); Providence Cancer Center, Earle A. Chiles Research Institute; Providence Health & Services; Mayo Clinic; Louisiana State University Health Sciences Center in New Orleans
Investigators ICMJE	Study Director: Bernard Fox, PhD UbiVac
PRS Account	UbiVac
Verification Date	July 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP