A Study of V934/V935 Vaccine in Cancer Patients With Selected Solid Tumors (V934-002 AM 4)

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00753415
First received: September 15, 2008
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

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. In Part A, participants will be assigned to get V935 vaccine alone or V934 and V935 vaccine. Part B is an optional part of the study, offering V934 vaccine boosts to participants who were enrolled in Part A.


Condition Intervention Phase
Non-Small Cell Lung Carcinoma
Breast Cancer
Melanoma
Upper GI Tract Carcinoma
Colon Carcinoma
Renal Cell Carcinoma
Bladder Carcinoma
Prostate Cancer
Biological: V935
Biological: V934
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Investigation of the Safety, Tolerability and Immunogenicity of V934/V935 hTERT Vaccination in Cancer Patients With Selected Solid Tumors

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of participants with adverse events (AEs) [ Time Frame: Day 1 up to Week 69 for Part A; 6 months from last vaccination for Part B. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with an immunologic response to V934/V935 [ Time Frame: From first vaccination up to 6 months after last vaccination. ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: August 2008
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A - Arm 1 V935 Biological: V935
A low-dose cohort will be enrolled first, then a high-dose cohort. V935 will be administered in 0.5 mL doses intramuscularly (IM) every 2 weeks for 2 doses followed by a 4-week observation period. In Part A, Arm 1, only V935 will be administered. In Part A, Arms 2 and 3, the two V935 doses will be administered after the 4 week observation period following the V934 doses.
Experimental: Part A - Arm 2 V934-EP (3 doses) + V935 Biological: V935
A low-dose cohort will be enrolled first, then a high-dose cohort. V935 will be administered in 0.5 mL doses intramuscularly (IM) every 2 weeks for 2 doses followed by a 4-week observation period. In Part A, Arm 1, only V935 will be administered. In Part A, Arms 2 and 3, the two V935 doses will be administered after the 4 week observation period following the V934 doses.
Biological: V934
The low-dose cohort will be enrolled first, then the high-dose cohort will be enrolled. Low-dose V934 will be administered in 0.5 mL doses IM followed by electroportation (EP) every 2 weeks for 3 doses, followed by a 4 week observation period. High-dose V934 will be administered 0.5 mL doses IM followed by EP every 2 weeks for 5 doses, followed by a 4 week observation period. V934 will be administered prior to V935 in Arms 2 and 3. In the optional V934 boost phase, V934 only will be administered in 0.5 mL doses IM every 2 weeks for 3 doses.
Experimental: Part A - Arm 3 V934-EP (5 doses) + V935 Biological: V935
A low-dose cohort will be enrolled first, then a high-dose cohort. V935 will be administered in 0.5 mL doses intramuscularly (IM) every 2 weeks for 2 doses followed by a 4-week observation period. In Part A, Arm 1, only V935 will be administered. In Part A, Arms 2 and 3, the two V935 doses will be administered after the 4 week observation period following the V934 doses.
Biological: V934
The low-dose cohort will be enrolled first, then the high-dose cohort will be enrolled. Low-dose V934 will be administered in 0.5 mL doses IM followed by electroportation (EP) every 2 weeks for 3 doses, followed by a 4 week observation period. High-dose V934 will be administered 0.5 mL doses IM followed by EP every 2 weeks for 5 doses, followed by a 4 week observation period. V934 will be administered prior to V935 in Arms 2 and 3. In the optional V934 boost phase, V934 only will be administered in 0.5 mL doses IM every 2 weeks for 3 doses.
Experimental: Part B - V934 Vaccine Boost Phase Biological: V934
The low-dose cohort will be enrolled first, then the high-dose cohort will be enrolled. Low-dose V934 will be administered in 0.5 mL doses IM followed by electroportation (EP) every 2 weeks for 3 doses, followed by a 4 week observation period. High-dose V934 will be administered 0.5 mL doses IM followed by EP every 2 weeks for 5 doses, followed by a 4 week observation period. V934 will be administered prior to V935 in Arms 2 and 3. In the optional V934 boost phase, V934 only will be administered in 0.5 mL doses IM every 2 weeks for 3 doses.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 and no evidence of progressive disease on routine evaluations prior to enrollment (with the exception for prostate carcinoma). 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 in participants who have completed definitive surgical resection and/or therapy no less than 8 weeks prior to protocol enrollment, but now have a biochemical-only relapse with a rising serum prostate-specific antigen (PSA) of >0.2 ng/mL after surgery or >1.5 ng/mL after radiation.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • 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 been previously treated with any human telomerase reverse-transcriptase (hTERT)-containing/targeted vaccine or any prior adenoviral or DNA vaccine.
  • Participant is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
  • Participant has known hypersensitivity to any component of study vaccine.
  • Participant has any laboratory value (with the exception of absolute lymphocyte count) at the time of study entry and prior to the first vaccine administration that would be considered Grade 3 or Grade 4 toxicity.
  • 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 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 (e.g., substances or treatments known to diminish immune response such as radiation, antimetabolites, alkylators, antilymphocytic sera, systemic corticosteroids) within 1 month prior to enrollment. Topical hydrocortisone up to a concentration of ≤1%, as well as participants receiving hormonal therapies (e.g., Lupron or Tamoxifen) or Herceptin, will be allowed.
  • Participant has known acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections. Participant must also have discontinued aspirin, NSAID, or any therapeutic warfarin or low molecular weight heparin at least 2 weeks prior to enrollment. Participants on prophylactic anticoagulant therapy such as low dose warfarin or heparin flush for in-dwelling catheters, or low dose, cardiac-protective aspirin may be enrolled providing they meet the coagulation entry parameters following discussion with the Sponsor.
  • The presence of Coombs positive serology at the time of entry.
  • 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 muscle group (deltoid, triceps, or thigh) that cannot be accessed with a 1.27 cm (1/2") needle.
  • Participant has been vaccinated for any disease or for prophylaxis within 1 month prior to the first vaccination.
  • Participant has any metal implants in the area of the injection site (e.g., shoulder implant, in the upper arms or shoulder girdle).
  • The participant has been diagnosed with Systemic Lupus Erythematosus (SLE) or has a positive antinuclear antibody (ANA) titer and 1 of the following: positive anti-double-stranded DNA antibodies, positive anti-Sm antibodies, or low C3 levels. Participants with a positive ANA screen and/or a positive ANA titer only can be admitted to the trial, if in the opinion of the Investigator, the participant does not meet the American College of Rheumatology (ACR) diagnostic criteria for SLE.
  • Participant with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with PSA <1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.

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 DNA-EP boost.
  • Prostrate cancer participants are allowed to have rising PSA levels.
  • Participant is allowed to have local advancement of a pre-existing tumor lesion documented in Part A of this study.
  • Patient has an ECOG performance status of 0 or 1.
  • Female participant of childbearing potential has a negative serum pregnancy test within 3 days of Part B study enrollment.

Exclusion criteria Part B

  • Participant has new or metastatic tumor lesions since enrollment in Part A.
  • Participant has any laboratory value (with the exception of absolute lymphocyte count) at the time of study entry and prior to the first vaccine administration that would be considered Grade 3 or Grade 4 toxicity.
  • 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 New York Heart Association (NYHA) Class III or IV congestive heart failure.
  • Participant must have no clinically significant ECG abnormalities and not have a pacemaker or cardioverter/defibrillator implanted.
  • Participant has undergone a splenectomy, or has developed any autoimmune disorders, since enrollment in Part A.
  • Participant has received immunosuppressive treatment (e.g., substances or treatments known to diminish immune response such as radiation, antimetabolites, alkylators, antilymphocytic sera, systemic corticosteroids) within 1 month prior to enrollment for Part B. Topical hydrocortisone up to a concentration of ≤1%, as well as participants receiving hormonal therapies (e.g., Lupron or Tamoxifen) or Herceptin, will be allowed.
  • Participant has developed any acquired, inherited, or idiopathic thrombocytopenia, platelet dysfunction or coagulopathy that would contraindicate IM injections, since enrollment in PART A. Participant must also have discontinued aspirin, NSAID, or any therapeutic warfarin or low molecular-weight heparin at least 2 weeks prior to enrollment in Part B. Participants on prophylactic anticoagulant therapy such as low dose warfarin or heparin flush for in-dwelling catheters, or low dose, cardiac-protective aspirin may be enrolled providing they meet the coagulation entry parameters, following discussion with the SPONSOR.
  • The presence of Coombs positive serology at the time of entry to Part B.
  • Participant has an acute infection requiring intravenous antibiotic, antiviral or antifungal agents within 2 weeks of entry to Part B.
  • Participant has developed an interval history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, since enrollment in Part A.
  • Participant has developed a psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial since enrollment in Part A.
  • Participant is, at the time of signing informed consent for enrollment in Part B, a regular user (including use of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
  • Participant is expecting to conceive at any time during the study or within 6 months 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 muscle group (deltoid, triceps, or thigh) that cannot be accessed with a 1.27 cm (1/2" needle length).
  • Participant has been vaccinated for any disease or for prophylaxis within 1 month prior to the first vaccination.
  • Participant has any metal implants in the area of the injection site (e.g., shoulder implant, in the upper arms or shoulder girdle).
  • Participant has been diagnosed with Systemic Lupus Erythematosus (SLE) or has a positive ANA titer and 1 of the following: positive anti-double-stranded DNA antibodies, positive anti-smooth muscle (Sm) antibodies, or low complement C3 levels, since enrollment in Part A.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Vice President, Late State Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT00753415     History of Changes
Other Study ID Numbers: V934-002, 2008_541
Study First Received: September 15, 2008
Last Updated: August 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
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

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Breast Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Lung Neoplasms
Melanoma
Prostatic Neoplasms
Colonic Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Kidney Neoplasms
Kidney Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on April 17, 2014