Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal Cancer
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ClinicalTrials.gov Identifier: NCT05898828 |
Recruitment Status :
Recruiting
First Posted : June 12, 2023
Last Update Posted : May 20, 2024
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Condition or disease | Intervention/treatment | Phase |
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Neoplasms Esophageal Neoplasms Esophagus Neoplasm Esophagus Cancer Neoplasms, Esophageal Esophageal Cancer (EsC) | Drug: Nivolumab Drug: Entinostat Biological: Montanide(R) ISA-51 VG Adjuvant Biological: H1299 Cell Lysates | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 50 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal Cancer |
Estimated Study Start Date : | May 23, 2024 |
Estimated Primary Completion Date : | December 30, 2034 |
Estimated Study Completion Date : | December 30, 2036 |
Arm | Intervention/treatment |
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Experimental: 1/ Phase I
H1299 cell lysate vaccine with Montanide(R) ISA-51 VG, entinostat, and nivolumab (Phase I component to determine lysate dose)
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Drug: Nivolumab
Nivolumab 480 mg flat dose via intravenous infusion on Day 3 of every cycle starting at Cycle 2, for intended duration of 1 year. Drug: Entinostat Entinostat (5 mg) self-administered on Days -14 and -7 prior to the first vaccination cycle, then entinostat (3 mg) self-administered on Days 1, 8, 15, and 22 of each vaccine cycle (Cycles 1-6). Entinostat continuation for subjects with immunologic response and NED during additional 2 vaccine injections. Biological: Montanide(R) ISA-51 VG Adjuvant H1299 cell lysate with Montanide(R) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mg lysate protein in 2-2.5 mL Montanide(R) ISA-51 VG adjuvant; lysate concentration will be 8-10 mg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED. Biological: H1299 Cell Lysates H1299 cell lysate with Montanide(R) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mg lysate protein in 2-2.5 mL Montanide(R) ISA-51 VG adjuvant; lysate concentration will be 8-10 mg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED. |
Experimental: 2/ Phase II
H1299 cell lysate vaccine with Montanide(R) ISA-51 VG, entinostat, and nivolumab (lysate at dose determined in Phase I)
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Drug: Nivolumab
Nivolumab 480 mg flat dose via intravenous infusion on Day 3 of every cycle starting at Cycle 2, for intended duration of 1 year. Drug: Entinostat Entinostat (5 mg) self-administered on Days -14 and -7 prior to the first vaccination cycle, then entinostat (3 mg) self-administered on Days 1, 8, 15, and 22 of each vaccine cycle (Cycles 1-6). Entinostat continuation for subjects with immunologic response and NED during additional 2 vaccine injections. Biological: Montanide(R) ISA-51 VG Adjuvant H1299 cell lysate with Montanide(R) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mg lysate protein in 2-2.5 mL Montanide(R) ISA-51 VG adjuvant; lysate concentration will be 8-10 mg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED. Biological: H1299 Cell Lysates H1299 cell lysate with Montanide(R) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mg lysate protein in 2-2.5 mL Montanide(R) ISA-51 VG adjuvant; lysate concentration will be 8-10 mg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED. |
- Phase I Component: To determine the safe dose of adjuvant H1299 lung cancer cell lysate vaccines with Montanide(R) ISA-51 VG administered in conjunction with entinostat and nivolumab in participants with locally advanced esophageal cancers (EsC)... [ Time Frame: before each cycle, every 2 weeks during Cycles 1 and 2 (AE only), at each treatment evaluation, and at the safety visit ]Assessment of safety and tolerability as determined by the frequency and severity of adverse events
- Phase II Component: To assess the frequency of immunologic responses to purified cancer-testis (CT) antigens in EsC participants receiving adjuvant vaccinations with H1299 cell lysate/Montanide(R) ISA-51 VG in combination with entinostat and niv... [ Time Frame: within 2 weeks prior to initiation of treatment, prior to 1st vaccination, 1 month following first 6 vaccinations, and every 6 months (24 weeks) during treatment continuation ]Assessment of immune response to CT antigens (new serologic reactivity or increase in existing antibody response to CT antigens, evidenced by IgM/IgG class switch or antibody titer)
- Phase I Component: To assess the frequency of immunologic responses to purified cancer-testis (CT) antigens in EsC participants receiving adjuvant vaccinations with H1299 cell lysate/Montanide(R) ISA-51 VG in combination with entinostat and nivo... [ Time Frame: within 2 weeks prior to initiation of treatment, prior to 1st vaccine, one month following the first six vaccinations (start of cycle 7), and every 6 months (24 weeks) during treatment continuation ]Analyses which investigate immunologic response (i.e., immune response to CT antigens); response to vaccine will be the appearance of new serologic reactivity or an increase in existing antibody response to CT antigens, evidenced by IgM/IgG class switch or antibody titer.
- Phase I + II Component: To assess safety of adjuvant H1299 lung cancer cell lysate vaccines with Montanide(R) ISA-51 VG administered in conjunction with entinostat and nivolumab in participants with locally advanced esophageal cancers (EsC) with... [ Time Frame: before each cycle, every 2 weeks between vaccines 1 and 2, at each treatment evaluation, and at the safety visit ]Assessment of safety and tolerability as determined by the frequency and severity of adverse events
- Phase II Component: To determine progression free survival (PFS) in EsC participants receiving the investigational adjuvant vaccine regimen [ Time Frame: every 12 weeks while on treatment or continued treatment, and during follow up every 3 months for 3 years, every 6 months for another 2 years or through disease progression ending at time of final PFS evaluation at 5 years post-enrollment ]Progression free survival (PFS) determined by RECIST using the Kaplan-Meier method
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Ages Eligible for Study: | 18 Years to 120 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
- Participants with clinical Stage II (T2/N0-N1; T3/N0) or Stage III (T1-T2/N2, T3/N1-N2) EsC per 8th edition TNM Staging System who have histologically documented or suspected residual disease in the esophagus or regional nodes following nCRT. Diagnosis must be confirmed by the NIH Laboratory of Pathology.
- No prior anti-PD1/anti-PD-L1 therapy for their EsC.
- Participant must be enrolled within 16 weeks following completion of nCRT or nCRT/surgery
- ECOG performance status of 0-1.
- 18 years of age or older
- Participant must be willing to co-enroll on 06C0014 (Prospective Analysis of Genetic and Epigenetic Alterations in Patients with Thoracic Malignancies) allowing for the use of tumor or normal tissues for correlative experiments pertaining to this protocol and related translational research efforts in the Thoracic Surgery Branch (TSB).
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Adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters (all eligibility assessment/enrollment bloodwork must be done at NIH no more than 2 weeks prior to initiation of study therapy):
- Absolute neutrophil count greater than 1500/mm^3
- Platelet count greater than 100,000/mm^3
- Hemoglobin greater than 8 g/dL (participants may receive transfusions to meet this parameter)
- INR <= 1.5 x ULN
- Total bilirubin <1.5 x upper limits of normal (except those with Gilberts disease)
- Serum creatinine less than or equal to 1.6 mg/mL or the eGFR (calculated per institutional standards) must be greater than 60 mL/min/1.73m^2
- Oxygen saturation equal to or greater than 92% on room air within 2 weeks of initiation of study therapy.
- Seronegative for HIV antibody by bloodwork performed at NIH no more than 4 weeks prior to initiation of study therapy.
- Seronegative for active hepatitis B, and seronegative for hepatitis C antibody by bloodwork performed at NIH no more than 4 weeks prior to initiation of study therapy. If hepatitis C antibody test is positive, then participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
- Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) within 28 days prior to initiation of study therapy, for the duration of study participation and up to 5 months after the last dose of study therapy.
- Participants who are breastfeeding or plan to breastfeed must agree to discontinue/postpone breastfeeding while receiving investigational treatment and for 5 months after the last dose study therapy.
- Participants must be able to understand and willing to sign an informed consent.
EXCLUSION CRITERIA:
- Participants who are receiving any other investigational agents
- Participants with a history of pneumonitis will be excluded unless cleared by Pulmonary Medicine consultants
- Participants requiring chronic systemic treatment with steroids above physiologic doses.
- Participants receiving warfarin anticoagulation, who cannot be transitioned to other agents such as enoxaparin or dabigatran, and for whom anticoagulants cannot be held for up to 24 hours.
- Participants with uncontrolled hypertension (>160/95) at screening, unstable coronary disease evidenced by EKG evidence of cardiac ischemia or uncontrolled arrhythmias, unstable angina, decompensated CHF (>NYHA Class II), or myocardial infarction within 6 months prior to initiation of study therapy.
- Participants with any of the following pulmonary function abnormalities: FEV, < 35% predicted; DLCO < 35% predicted (post-bronchodilator); based on assessment performed no more than 4 weeks prior to initiation of study therapy.
- Participant pregnancy.
- Other malignancy requiring treatment with the exception of localized skin cancer amenable to topical therapies
- Uncontrolled intercurrent illness occurring within 3 months prior to initiation of study therapy that would limit compliance with study requirements. Intercurrent illness may include any conditions uncovered during screening assessments (physical examination, laboratory assessments, etc.) that, in the judgment of the investigator, precludes participation because it could present disproportionate risk to the participant
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): NCT05898828
Contact: Deneise Francis, R.N. | (240) 858-3974 | deneise.francis@nih.gov | |
Contact: David S Schrump, M.D. | (240) 760-6239 | david_schrump@nih.gov |
United States, Maryland | |
National Institutes of Health Clinical Center | Recruiting |
Bethesda, Maryland, United States, 20892 | |
Contact: National Cancer Institute Referral Office 888-624-1937 |
Principal Investigator: | David S Schrump, M.D. | National Cancer Institute (NCI) |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT05898828 |
Other Study ID Numbers: |
10001544 001544-C |
First Posted: | June 12, 2023 Key Record Dates |
Last Update Posted: | May 20, 2024 |
Last Verified: | April 17, 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | .All IPD recorded will be shared upon request. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) |
Time Frame: | Data from this study may be requested from other researchers after the trial has been completed and closed. |
Access Criteria: | Data from this study may be requested by contacting the PI. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Cell Mediated Response immune subsets peripheral immune subsets CT antigens |
neoadjuvant chemoradiation therapy (nCRT) H1299 Cell Lysates EsC Immunotherapy |
Neoplasms Esophageal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Head and Neck Neoplasms Digestive System Diseases Esophageal Diseases Gastrointestinal Diseases Nivolumab Entinostat |
Monatide (IMS 3015) Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Histone Deacetylase Inhibitors Enzyme Inhibitors |