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Trial record 3 of 226 for:    Vigil

Trial of Atezolizumab and Vigil for Advanced Gynecological Cancers (A Companion Study to CL-PTL-119)

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ClinicalTrials.gov Identifier: NCT03073525
Recruitment Status : Recruiting
First Posted : March 8, 2017
Last Update Posted : May 23, 2018
Sponsor:
Collaborator:
Roche-Genentech
Information provided by (Responsible Party):
Gradalis, Inc.

Brief Summary:
This is a crossover study of Vigil, Atezolizumab and their combination in patients who have tumor harvested at surgery and successful manufacturing of Vigil but are ineligible for CL-PTL-119 (the VITAL study) or previously randomized to placebo.

Condition or disease Intervention/treatment Phase
Advanced Gynecological Cancers Ovarian Cancer Cervical Cancer Uterine Cancer Biological: Vigil Drug: Atezolizumab Phase 2

Detailed Description:

This is a randomized, open label intra-patient crossover study of Vigil, the checkpoint inhibitor Atezolizumab and the combination of the two agents, in patients with epithelial ovarian cancer, or other gynecological cancers (i.e., cervical, uterine). Eligible patients will be randomized to receive two cycles of Vigil alone or two cycles of atezolizumab alone, followed by combination treatment with the two agents.

This study is intended as a companion study to protocol CL-PTL-119, A Randomized, Double Blind, Placebo Controlled Phase 3 trial of Vigil Engineered Autologous Tumor Cell Immunotherapy in Subjects with Stage IIIb-IV Ovarian Cancer in Clinical Complete Response following Surgery and Primary Chemotherapy, otherwise known as the VITAL study. Patients who have tumor harvested at surgery and Vigil successfully manufactured, but then are ineligible for randomization onto the VITAL study or previously randomized to placebo, will be offered the opportunity to participate in this protocol.

Subjects enrolled will either be:

• Patients with recurrent disease, undergoing a standard surgical procedure (e.g. surgical debulking, palliative resection, malignant ascites or others) will have tumor procured for manufacture of Vigil.

OR

  • Patients with ovarian cancer who failed to meet the eligibility criteria for Protocol CL-PTL-119 because of failure to achieve a complete clinical response following primary debulking surgery and standard paclitaxel/carboplatin therapy, OR
  • Patients who fail to meet the eligibility criteria for Protocol CL-PTL-119 because of a histologic diagnosis of another gynecological cancer (i.e., cervical, uterine) and not ovarian cancer.

OR

• Patients who were randomized on Protocol CL-PTL 119 and were subsequently unblinded at recurrence and were assigned to the placebo arm.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Eligible patients will be randomized to receive two cycles of either Vigil alone or Atezolizumab alone, then followed by combination treatment with the two agents.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Intra-patient Crossover, Safety, Biomarker and Anti-Tumor Activity Assessment of the Combination of Atezolizumab and Vigil in Patients With Advanced Gynecological Cancers
Actual Study Start Date : May 25, 2017
Estimated Primary Completion Date : October 1, 2018
Estimated Study Completion Date : April 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Vigil then Vigil + Atezolizumab
Vigil immunotherapy will be administered at a concentration of 1x10e7 cells/dose given via intradermal injection every 3 weeks for a minimum of 4 doses and a maximum of 12 doses for 2 cycles (1 cycle = 21 days). Combination of Vigil and Atezolizumab thereafter with maximum duration of 36 weeks, inclusive of monotherapy and combination therapy.
Biological: Vigil
Vigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms (TGFβ-1 and TGFβ-2).
Other Names:
  • Engineered Autologous Tumor Cell Immunotherapy
  • Gemogenovatucel-T
  • FANG
  • IND14205

Drug: Atezolizumab
Atezolizumab is provided in a single-use, 20-cc USP/Ph. Eur. Type 1 glass vial as a colorless to slightly-yellow, sterile, preservative-free clear liquid solution intended for IV administration. The vial is designed to deliver 20 mL (1200 mg) of atezolizumab solution but may contain more than the stated volume to enable delivery of the entire 20 mL volume. The atezolizumab drug product is formulated as 60 mg/mL atezolizumab in 20 mM histidine acetate, 120 mM sucrose, 0.04% polysorbate 20, pH 5.8 (Phase III formulation).
Other Names:
  • TECENTRIQ™
  • MPDL3280A

Active Comparator: Atezolizumab then Vigil + Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg as an intravenous infusion every 3 weeks for 2 cycles (1 cycle = 21 days). The initial dose is to be administered over one hour and if well tolerated, subsequent infusions may be administered over 30 minutes. Combination of Vigil and Atezolizumab thereafter with maximum duration of 36 weeks, inclusive of monotherapy and combination therapy.
Biological: Vigil
Vigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms (TGFβ-1 and TGFβ-2).
Other Names:
  • Engineered Autologous Tumor Cell Immunotherapy
  • Gemogenovatucel-T
  • FANG
  • IND14205

Drug: Atezolizumab
Atezolizumab is provided in a single-use, 20-cc USP/Ph. Eur. Type 1 glass vial as a colorless to slightly-yellow, sterile, preservative-free clear liquid solution intended for IV administration. The vial is designed to deliver 20 mL (1200 mg) of atezolizumab solution but may contain more than the stated volume to enable delivery of the entire 20 mL volume. The atezolizumab drug product is formulated as 60 mg/mL atezolizumab in 20 mM histidine acetate, 120 mM sucrose, 0.04% polysorbate 20, pH 5.8 (Phase III formulation).
Other Names:
  • TECENTRIQ™
  • MPDL3280A




Primary Outcome Measures :
  1. Number of treatment-emergent AEs of Vigil + Atezolizumab [ Time Frame: Up to 30 days after last treatment ]
    The safety evaluation will include collection of AEs, AESIs and SAEs from baseline to 30 days after treatment. These AEs will be graded according to the NCI CTCAE v4.03.


Secondary Outcome Measures :
  1. ELISPOT conversion rate to Vigil alone, Atezolizumab alone and Vigil + Atezolizumab [ Time Frame: Up to 30 days after last treatment ]
    Whole blood for correlative studies (ELISPOT and ctDNA) will be obtained at baseline, at the start of cycle 3 (the first cycle of combination therapy) and every 3 cycles thereafter.

  2. Radiological Tumor Assessment [ Time Frame: Up to 30 days after last treatment ]
    In patients with measureable disease, anti-tumor activity as assessed by RECIST 1.1 criteria, will also be summarized and correlated to baseline tumor mutation burden, baseline PDL-1 expression, post treatment TIL infiltration, change in PDL-1 expression and circulating ELISPOT response. Radiological assessment of tumor response will be performed at baseline, at the end of cycle 2 of single agent therapy and every third cycle thereafter. Tumor biopsy for correlative studies including scoring of tumor infiltrating lymphocyte (TIL) and PD-1 / PDL1 expression analysis will be obtained at tissue procurement and at any time after the end of cycle 3.

  3. Time to Progression [ Time Frame: Up to 3 years ]
    Overall assessment of time to progression and survival will be measured by Radiological Tumor Assessment. This will be performed at baseline, at the end of Cycle 2 of single agent therapy and every third cycle thereafter, and at End of Treatment. Survival will be followed annually for 3 years.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Tissue Procurement Inclusion Criteria:

Subjects will be eligible for tissue procurement for the Vigil manufacturing process, if they meet all of the following criteria:

  1. Histologically confirmed Stage IIIb, IIIc or IV high-grade papillary serous, clear cell, or endometrioid ovarian, fallopian tube or primary peritoneal carcinoma
  2. Age ≥ 18 years.
  3. Estimated survival ≥ 6 months.
  4. ECOG Performance Status ≤ 1
  5. Metastatic disease
  6. Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative soft-tissue mass of ~10-30 grams tissue ("grape" to "golf-ball" size) or ascites fluid estimated volume ≥ 500mL (from a primary or secondary paracentesis, yielding in a high volume of tumor cells) for immunotherapy manufacture.
  7. Tumor intended for immunotherapy manufacture is not embedded in bone and does not contain luminal tissue (e.g. bowel, ureter, bile duct).
  8. Presence of at least one additional site of disease that is RECIST 1.1 evaluable/measurable.
  9. Ability to understand and the willingness to sign a written informed protocol specific consent for tissue harvest or a parental/guardian informed consent and pediatric assent when appropriate.

Tissue Procurement Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for tissue procurement for the Vigil manufacturing:

  1. Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for < 30 days duration.
  2. Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
  3. Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
  4. Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids.
  5. Known HIV or chronic Hepatitis B or C infection.
  6. Known history of allergies or sensitivities to gentamicin.
  7. History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.

Study Enrollment Inclusion Criteria:

Subjects will be eligible for registration into the trial if they meet all of the following inclusion criteria:

  1. Successful manufacturing of at least 4 vials of Vigil.
  2. One of the following:

    1. Failure to meet the eligibililty criteria for Protocol CL-PTL-119 due to i) histology of ovarian cancer and failure to achieve a complete clinical response following primary debulking surgery and standard paclitaxel/carboplatin therapy OR, ii) a histologic diagnosis of another gynecologic malignancy which is not ovarian cancer.
    2. Recurrent ovarian cancer.
    3. Randomized on Protocol CL-PTL-119 and were subsequently unblinded at recurrence and were assigned to the placebo arm.
  3. ECOG performance status (PS) ≤ 1
  4. Estimated survival ≥ 6 months.
  5. Measureable or evaluable disease.
  6. Adequate organ and bone marrow function as defined below:

    1. Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L (1500 per mm^3)
    2. Platelets >100 × 10e9/L (100,000 per mm^3)
    3. Hemoglobin ≥9.0 g/dL (5.59 mmol/L)
    4. Creatinine clearance (CrCL) >50 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance:

      Females:

      CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL)

    5. Serum bilirubin ≤1.5 × upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of hemolysis or hepatic pathology) who will be allowed in consultation with their physician.
    6. AST and ALT ≤2.5 × ULN in patients with no liver metastasis
    7. AST or ALT ≤5 × ULN in patients with liver metastasis
    8. TSH within institutional limits. If TSH is greater or less than institutional limits patients may participate if their T4 is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed
  7. Subject has recovered to CTCAE Grade 1 or better from all adverse events associated with prior therapy or surgery
  8. Pre-existing motor or sensory neurologic pathology or symptoms must be recovered to CTCAE Grade 2 or better
  9. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the IPs may be included (e.g., hearing loss) after consultation with the Principal Investigator
  10. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) prior to tissue procurement and at least 21 days prior to the first dose of study drug (at least 21 days prior to the first dose of study drug for subjects who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C).
  11. Subjects who are not rendered surgically sterile as a result of surgery for ovarian cancer, must have, negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry.
  12. Ability to understand and the willingness to sign a written informed protocol specific consent.
  13. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Study Enrollment Exclusion Criteria:

Subjects will NOT be eligible for study registration and enrollment if meeting any of the following criteria:

  1. Have received more than two additional chemotherapy regimens for recurrent ovarian cancer, after their initial treatment with paclitaxel/carboplatin, OR have received more than two additional chemotherapy regimens for the treatment of another gynecologic malignancy

    1. Patients must have fully recovered from chemotherapy associated toxicities prior to starting treatment on this protocol.
    2. Palliative radiotherapy is permitted provided:

    i. More than 3 weeks have elapsed between the end of radiotherapy and the first dose of study therapy, AND ii. The lung is not in the radiation field, AND iii. The irradiated lesion(s) cannot be used as target lesions.

  2. Participation in another clinical study with an investigational product within the last 3 weeks prior to study start.
  3. Patients with autoimmune diseases are excluded from enrollment with the exception of patients with hypothyroidism on stable thyroxine replacement, and patients with T1DM on stable insulin replacement.
  4. Receipt of steroid therapy within the 2 weeks of the first dose of study therapy.
  5. Live vaccine used for the prevention of infectious disease administered < 30 days prior to the start of study therapy. NOTE: Subjects, if enrolled, should not receive live vaccine during the study and for 5 months after the last dose of atezolizumab.
  6. Post-surgery complication that in the opinion of the treating investigator would interfere with the subject's study participation or make it not in the best interest of the subject to participate.
  7. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
  8. Female subjects who are pregnant, breast-feeding or of reproductive potential who are not employing an effective method of birth control defined in the protocol. Effective contraception is required for women receiving atezolizumab for 5 months after the last dose.
  9. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03073525


Contacts
Contact: Gladice Wallraven 214-442-8124 info@gradalisinc.com

Locations
United States, Alabama
University of South Alabama Mitchell Cancer Institute Recruiting
Mobile, Alabama, United States, 36604
Contact: Rodney Rocconi, MD    251-665-8000    rocconi@health.southalabama.edu   
Principal Investigator: Rodney Rocconi, MD         
United States, Georgia
Augusta University Recruiting
Augusta, Georgia, United States, 30912
Contact: Lisa Hatch, RN    706-721-4805    lhatch@augusta.edu   
Principal Investigator: Sharad A Ghamande, MD         
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Nicole Leon, RN    313-916-6781    sleon9@hfhs.org   
Principal Investigator: Adnan Munkarah, MD         
United States, Montana
Billings Clinic Recruiting
Billings, Montana, United States, 59101
Contact: Kathy Wilkinson, RN BSN OCN    406-435-7415    kwilkinson@billingsclinic.org   
Principal Investigator: Erin Stevens, MD         
United States, New Hampshire
Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Kathy Phipps, CCRP    603-653-3537    kathy.phipps@hitchcock.org   
Principal Investigator: Leslie DeMars, MD         
United States, South Carolina
GHS Cancer Institute Recruiting
Greenville, South Carolina, United States, 29605
Contact: Gina Norris    864-241-6251    gnorris@ghs.org   
Principal Investigator: Jeffrey Elder, MD         
Sponsors and Collaborators
Gradalis, Inc.
Roche-Genentech
Investigators
Study Director: Luisa Manning, MD Gradalis, Inc.

Publications:
Senzer N, Barve M, Nemunaitis J, Kuhn J, Melnyk A, et al. (2013) Long Term Follow Up: Phase I Trial of "Bi-Shrnafurin/GMCSF DNA/Autologous Tumor Cell" Immunotherapy (FANG™) in Advanced Cancer. J Vaccines Vaccin 4:209. doi:10.4172/2157-7560.1000209

Responsible Party: Gradalis, Inc.
ClinicalTrials.gov Identifier: NCT03073525     History of Changes
Other Study ID Numbers: CL-PTL-126
First Posted: March 8, 2017    Key Record Dates
Last Update Posted: May 23, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gradalis, Inc.:
Stage IIIb
Stage IV
Ovarian Cancer
Cervical Cancer
Uterine Cancer
Immunotherapy

Additional relevant MeSH terms:
Modafinil
Armodafinil
Ovarian Neoplasms
Uterine Cervical Neoplasms
Uterine Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Cervical Diseases
Uterine Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action