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A Study of V934/V935 Vaccine in Cancer Participants With Selected Solid Tumors (V934-002)

Primary Purpose

Non-Small Cell Lung Carcinoma, Breast Cancer, Melanoma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
V935
V934-EP
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Carcinoma focused on measuring Urinary Bladder Neoplasms, Breast Neoplasms, Renal Cell carcinoma, Melanoma, Prostatic Neoplasms, Colonic Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Urinary Bladder Diseases, Urologic Diseases, Breast Diseases, Skin Diseases, Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type, Adenocarcinoma, Kidney Neoplasms, Kidney Diseases, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms, Nerve Tissue, Nevi and Melanomas, Genital Neoplasms, Male Genital Diseases, Male, Prostatic Diseases, Colorectal Neoplasms, Intestinal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Part A

  • Participant has one of the selected solid tumors with no distant metastases, and is more than 8 weeks from completion of definitive therapy with intention to cure. Selected Solid Tumors: Stage I to III non-small cell lung carcinoma (NSCLC); Stage III breast cancer; Stage IIB or III melanoma; Stage II or III upper gastrointestinal tract carcinoma (e.g., esophagus, stomach, gallbladder, pancreas); Stage III colon carcinoma; Stage II, III, or IV (M0 only) renal cell carcinoma; Stage II, III, or IV (M0 only) bladder carcinoma; clinically-localized prostate carcinoma
  • Participant has adequate organ function.
  • Female participant of childbearing potential has a negative serum pregnancy test within 3 days of study enrollment.

Exclusion Criteria Part A

  • Participant has known hypersensitivity to any component of study vaccine.
  • Participant has a history of clinically significant cardiac conditions, including cardiac arrhythmias which have not been controlled within the last 3 months, unstable angina, myocardial infarction (within the last 3 months), or New York Heart Association (NYHA) Class III or IV congestive heart failure. Participant must have no clinically significant electrocardiogram (ECG) abnormalities and not have a pacemaker or cardioverter/defibrillator implanted.
  • Participant has undergone splenectomy or has any history of autoimmune disorder.
  • Participant has received immunosuppressive treatment within 1 month prior to enrollment.
  • Participant has known acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections.
  • Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of study entry.
  • Participant is pregnant or breastfeeding, or expecting to conceive at any time during the study or within 1 year after receiving the last vaccination.
  • Participant is known to be Human Immunodeficiency Virus (HIV)-seropositive.
  • Participant has known history of Hepatitis B or C or active Hepatitis A.
  • Participant has been vaccinated for any disease or for prophylaxis within 1 month prior to the first vaccination.
  • The participant has been diagnosed with Systemic Lupus Erythematosus (SLE)

Inclusion Criteria Part B

  • Participant must have completed their respective vaccination Treatment Group regimen for Part A of this study.
  • Participant must have completed a ≥12 week safety observation period prior to receiving their first V934-EP boost.

Exclusion Criteria Part B

  • Participant has new or metastatic tumor lesions since enrollment in Part A.
  • Participant has developed any significant cardiac conditions since enrollment in Part A including cardiac arrhythmias which have not been controlled within the last 3 months, unstable angina, myocardial infarction (within the last 3 months), or NYHA Class III or IV congestive heart failure.
  • Participant has undergone a splenectomy, or has developed any autoimmune disorders, since enrollment in Part A.
  • Participant has received immunosuppressive treatment within 1 month prior to enrollment in Part B
  • Participant has developed any acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections
  • Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of entry to Part B.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm 6

    Arm 7

    Arm 8

    Arm 9

    Arm 10

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Part A: V935 LD

    Part A: V934 LD(3)+V935 LD

    Part A: V935 HD

    Part A: V934 HD(3)+V935 HD

    Part A: V934 HD(5)+V935 HD

    Part B: V935 LD/V934 Booster

    Part B: V934 LD(3)+V935 LD/V934 Booster

    Part B: V935 HD/V934 Booster

    Part B: V934 HD(3)+V935 HD/V934 Booster

    Part B: V934 HD(5)+V935 HD/V934 Booster

    Arm Description

    Two intramuscular (IM) injections of V935 low dose (LD), 1 given every other week over a 3-week period.

    Three electroporation (EP) injections of V934 (LD) , 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (LD) will be administered, 1 given every other week over a 3-week period.

    Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.

    Three EP injections of V934 (HD), 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) will be administered, 1 given every other week over a 3-week period.

    Five EP injections of V934 (HD), 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) will be administered, 1 given every other week over a 3-week period.

    Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.

    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.

    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.

    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.

    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.

    Outcomes

    Primary Outcome Measures

    Number of Participants With Dose-Limiting Toxicity (DLT)
    DLT was defined as a vaccine- or EP-related adverse event (AE) including the following: Hematological (Grade 3 neutropenia with fever, Grade 4 neutropenia ≥5 days, Grade 4 thrombocytopenia) or non-hematological AE, Grade 3, 4 or 5 with the exception of Grade 3 nausea, vomiting, diarrhea or serum glutamic oxaloacetic transaminase (SGOT) elevation, alopecia, Grade 3/4 creatinine phosphokinase (CPK) elevation or inadequately treated hypersensitivity. Any Grade 3/4 related AE that failed to return to ≤Grade 1 or baseline within 14 days was also considered a DLT.
    Number of Participants With Adverse Events (AEs)
    This analysis includes the number of participants with AEs and serious AEs (SAEs) during the Treatment Period plus the Acute Follow-up (FU) Period (up to 30 days following last vaccination). An AE was defined as any unfavorable or unintended change in the structure, function or chemistry of the body temporally associated with the use of the product, whether or not considered related to the product, including any worsening of a preexisting condition which was temporally associated with the product. An SAE was defined as an AE resulting in death, was life-threatening, resulted in or prolonged hospitalization, was a congenital anomaly, a cancer, an overdose or other important medical event.

    Secondary Outcome Measures

    Number of Participants With Immunologic Response to V934/V935 (Immunologic Response Rate)
    An Enzyme-Linked Immunosorbent Spot (ELISPOT) assay was planned to be used to demonstrate a cell mediated immune response to V935 and/or V934 in vaccinated participants. Collection of Peripheral Blood Mononuclear Cells (PBMCs) and serum took place at baseline (Screening and pre-vaccination Day 1), and various time points post vaccination across the three distinct regimens to be tested. A positive immune response was to be defined by a minimum number of spot-forming cells per million PBMC (SFC/10^6 PBMCs) for the antigen well and a minimum n-fold increase in the antigen well over the control well.

    Full Information

    First Posted
    September 15, 2008
    Last Updated
    February 26, 2015
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00753415
    Brief Title
    A Study of V934/V935 Vaccine in Cancer Participants With Selected Solid Tumors (V934-002)
    Official Title
    A Phase I Investigation of the Safety, Tolerability and Immunogenicity of V934/V935 hTERT Vaccination in Cancer Patients With Selected Solid Tumors
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    August 2008 (undefined)
    Primary Completion Date
    April 2011 (Actual)
    Study Completion Date
    April 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a two-part study to test the safety, tolerability, and immune response for V934/V935 vaccine using a new prime-boost regimen in participants with selected solid tumors.
    Detailed Description
    Two vaccines will be administered: V934-electroporation (EP) either low dose (LD) or high dose (HD), and V935 either LD or HD. In Part A, participants will be assigned to V935 vaccine alone or in combination with V934-EP. Part B will be an optional part of the study, offering V934-EP vaccine booster to participants who were enrolled in Part A.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Non-Small Cell Lung Carcinoma, Breast Cancer, Melanoma, Upper GI Tract Carcinoma, Colon Carcinoma, Renal Cell Carcinoma, Bladder Carcinoma, Prostate Cancer
    Keywords
    Urinary Bladder Neoplasms, Breast Neoplasms, Renal Cell carcinoma, Melanoma, Prostatic Neoplasms, Colonic Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Urinary Bladder Diseases, Urologic Diseases, Breast Diseases, Skin Diseases, Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type, Adenocarcinoma, Kidney Neoplasms, Kidney Diseases, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms, Nerve Tissue, Nevi and Melanomas, Genital Neoplasms, Male Genital Diseases, Male, Prostatic Diseases, Colorectal Neoplasms, Intestinal Neoplasms

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    37 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Part A: V935 LD
    Arm Type
    Experimental
    Arm Description
    Two intramuscular (IM) injections of V935 low dose (LD), 1 given every other week over a 3-week period.
    Arm Title
    Part A: V934 LD(3)+V935 LD
    Arm Type
    Experimental
    Arm Description
    Three electroporation (EP) injections of V934 (LD) , 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (LD) will be administered, 1 given every other week over a 3-week period.
    Arm Title
    Part A: V935 HD
    Arm Type
    Experimental
    Arm Description
    Two IM injections of V935 high dose (HD), 1 given very other week over a 3-week period.
    Arm Title
    Part A: V934 HD(3)+V935 HD
    Arm Type
    Experimental
    Arm Description
    Three EP injections of V934 (HD), 1 given every other week over a 5-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) will be administered, 1 given every other week over a 3-week period.
    Arm Title
    Part A: V934 HD(5)+V935 HD
    Arm Type
    Experimental
    Arm Description
    Five EP injections of V934 (HD), 1 given every other week over a 9-week period. Following a 4-week observation period, 2 IM injections of V935 (HD) will be administered, 1 given every other week over a 3-week period.
    Arm Title
    Part B: V935 LD/V934 Booster
    Arm Type
    Experimental
    Arm Description
    Participants who completed Part A could enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster were administered, 1 given every 2 weeks.
    Arm Title
    Part B: V934 LD(3)+V935 LD/V934 Booster
    Arm Type
    Experimental
    Arm Description
    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.
    Arm Title
    Part B: V935 HD/V934 Booster
    Arm Type
    Experimental
    Arm Description
    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.
    Arm Title
    Part B: V934 HD(3)+V935 HD/V934 Booster
    Arm Type
    Experimental
    Arm Description
    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.
    Arm Title
    Part B: V934 HD(5)+V935 HD/V934 Booster
    Arm Type
    Experimental
    Arm Description
    Participants who complete Part A can enter Part B. Following a 12-week observation period, 3 EP injections of V934 booster will be administered, 1 given every 2 weeks.
    Intervention Type
    Biological
    Intervention Name(s)
    V935
    Intervention Description
    A 0.5 mL vaccine administered IM every 2 weeks as either a LD (1 x 10^9 vector genomes/mL) or a HD (1 x 10^11 vector genomes/mL).
    Intervention Type
    Biological
    Intervention Name(s)
    V934-EP
    Intervention Description
    A 0.5 mL vaccine administered by EP as either a LD (0.5 mg plasmid/mL) or a HD (5.0 mg plasmid/mL).
    Primary Outcome Measure Information:
    Title
    Number of Participants With Dose-Limiting Toxicity (DLT)
    Description
    DLT was defined as a vaccine- or EP-related adverse event (AE) including the following: Hematological (Grade 3 neutropenia with fever, Grade 4 neutropenia ≥5 days, Grade 4 thrombocytopenia) or non-hematological AE, Grade 3, 4 or 5 with the exception of Grade 3 nausea, vomiting, diarrhea or serum glutamic oxaloacetic transaminase (SGOT) elevation, alopecia, Grade 3/4 creatinine phosphokinase (CPK) elevation or inadequately treated hypersensitivity. Any Grade 3/4 related AE that failed to return to ≤Grade 1 or baseline within 14 days was also considered a DLT.
    Time Frame
    Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period
    Title
    Number of Participants With Adverse Events (AEs)
    Description
    This analysis includes the number of participants with AEs and serious AEs (SAEs) during the Treatment Period plus the Acute Follow-up (FU) Period (up to 30 days following last vaccination). An AE was defined as any unfavorable or unintended change in the structure, function or chemistry of the body temporally associated with the use of the product, whether or not considered related to the product, including any worsening of a preexisting condition which was temporally associated with the product. An SAE was defined as an AE resulting in death, was life-threatening, resulted in or prolonged hospitalization, was a congenital anomaly, a cancer, an overdose or other important medical event.
    Time Frame
    Day 1 up to 30 days following the last vaccination (up to 77 weeks); Treatment Period + Acute Follow-up (FU) Period
    Secondary Outcome Measure Information:
    Title
    Number of Participants With Immunologic Response to V934/V935 (Immunologic Response Rate)
    Description
    An Enzyme-Linked Immunosorbent Spot (ELISPOT) assay was planned to be used to demonstrate a cell mediated immune response to V935 and/or V934 in vaccinated participants. Collection of Peripheral Blood Mononuclear Cells (PBMCs) and serum took place at baseline (Screening and pre-vaccination Day 1), and various time points post vaccination across the three distinct regimens to be tested. A positive immune response was to be defined by a minimum number of spot-forming cells per million PBMC (SFC/10^6 PBMCs) for the antigen well and a minimum n-fold increase in the antigen well over the control well.
    Time Frame
    From pre-vaccination to Week 69

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria Part A Participant has one of the selected solid tumors with no distant metastases, and is more than 8 weeks from completion of definitive therapy with intention to cure. Selected Solid Tumors: Stage I to III non-small cell lung carcinoma (NSCLC); Stage III breast cancer; Stage IIB or III melanoma; Stage II or III upper gastrointestinal tract carcinoma (e.g., esophagus, stomach, gallbladder, pancreas); Stage III colon carcinoma; Stage II, III, or IV (M0 only) renal cell carcinoma; Stage II, III, or IV (M0 only) bladder carcinoma; clinically-localized prostate carcinoma Participant has adequate organ function. Female participant of childbearing potential has a negative serum pregnancy test within 3 days of study enrollment. Exclusion Criteria Part A Participant has known hypersensitivity to any component of study vaccine. Participant has a history of clinically significant cardiac conditions, including cardiac arrhythmias which have not been controlled within the last 3 months, unstable angina, myocardial infarction (within the last 3 months), or New York Heart Association (NYHA) Class III or IV congestive heart failure. Participant must have no clinically significant electrocardiogram (ECG) abnormalities and not have a pacemaker or cardioverter/defibrillator implanted. Participant has undergone splenectomy or has any history of autoimmune disorder. Participant has received immunosuppressive treatment within 1 month prior to enrollment. Participant has known acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections. Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of study entry. Participant is pregnant or breastfeeding, or expecting to conceive at any time during the study or within 1 year after receiving the last vaccination. Participant is known to be Human Immunodeficiency Virus (HIV)-seropositive. Participant has known history of Hepatitis B or C or active Hepatitis A. Participant has been vaccinated for any disease or for prophylaxis within 1 month prior to the first vaccination. The participant has been diagnosed with Systemic Lupus Erythematosus (SLE) Inclusion Criteria Part B Participant must have completed their respective vaccination Treatment Group regimen for Part A of this study. Participant must have completed a ≥12 week safety observation period prior to receiving their first V934-EP boost. Exclusion Criteria Part B Participant has new or metastatic tumor lesions since enrollment in Part A. Participant has developed any significant cardiac conditions since enrollment in Part A including cardiac arrhythmias which have not been controlled within the last 3 months, unstable angina, myocardial infarction (within the last 3 months), or NYHA Class III or IV congestive heart failure. Participant has undergone a splenectomy, or has developed any autoimmune disorders, since enrollment in Part A. Participant has received immunosuppressive treatment within 1 month prior to enrollment in Part B Participant has developed any acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of entry to Part B.

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    32000810
    Citation
    Aurisicchio L, Fridman A, Mauro D, Sheloditna R, Chiappori A, Bagchi A, Ciliberto G. Safety, tolerability and immunogenicity of V934/V935 hTERT vaccination in cancer patients with selected solid tumors: a phase I study. J Transl Med. 2020 Jan 30;18(1):39. doi: 10.1186/s12967-020-02228-9.
    Results Reference
    derived

    Learn more about this trial

    A Study of V934/V935 Vaccine in Cancer Participants With Selected Solid Tumors (V934-002)

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