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Testing the Addition of the Anti-cancer Viral Therapy Telomelysin™ to Chemoradiation for Patients With Advanced Esophageal Cancer and Are Not Candidates for Surgery

NCT04391049

Description:

This phase I trial studies the side effects of OBP-301 when given together with carboplatin, paclitaxel, and radiation therapy in treating patients with esophageal or gastroesophageal cancer that invades local or regional structures. OBP-301 is a virus that has been designed to infect and destroy tumor cells (although there is a small risk that it can also infect normal cells). Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving OBP-301 with chemotherapy and radiation therapy may work better than standard chemotherapy and radiation therapy in treating patients with esophageal or gastroesophageal cancer.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Testing the Addition of the Anti-cancer Viral Therapy Telomelysin™ to Chemoradiation for Patients With Advanced Esophageal Cancer and Are Not Candidates for Surgery
  • Official Title: Phase I Trial With Expansion Cohort of OBP-301 (Telomelysin™) and Definitive Chemoradiation for Patients With Locally Advanced Esophageal and Gastroesophageal Adenocarcinoma Who Are Not Candidates for Surgery

Clinical Trial IDs

  • ORG STUDY ID: NRG-GI007
  • SECONDARY ID: NCI-2020-02320
  • SECONDARY ID: NRG-GI007
  • SECONDARY ID: NRG-GI007
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT04391049

Conditions

  • Advanced Esophageal Adenocarcinoma
  • Advanced Gastroesophageal Junction Adenocarcinoma
  • Clinical Stage II Esophageal Adenocarcinoma AJCC v8
  • Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Clinical Stage IIA Esophageal Adenocarcinoma AJCC v8
  • Clinical Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Clinical Stage IIB Esophageal Adenocarcinoma AJCC v8
  • Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Clinical Stage III Esophageal Adenocarcinoma AJCC v8
  • Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage II Esophageal Adenocarcinoma AJCC v8
  • Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IIA Esophageal Adenocarcinoma AJCC v8
  • Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IIB Esophageal Adenocarcinoma AJCC v8
  • Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage III Esophageal Adenocarcinoma AJCC v8
  • Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8
  • Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8
  • Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage II Esophageal Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage III Esophageal Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IIIA Esophageal Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IIIB Esophageal Adenocarcinoma AJCC v8
  • Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8
  • Unresectable Gastroesophageal Junction Adenocarcinoma

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (OBP-301, carboplatin, paclitaxel, radiation)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratTreatment (OBP-301, carboplatin, paclitaxel, radiation)
Telomerase-specific Type 5 Adenovirus OBP-301OBP-301, Telomelysin ™Treatment (OBP-301, carboplatin, paclitaxel, radiation)

Purpose

This phase I trial studies the side effects of OBP-301 when given together with carboplatin, paclitaxel, and radiation therapy in treating patients with esophageal or gastroesophageal cancer that invades local or regional structures. OBP-301 is a virus that has been designed to infect and destroy tumor cells (although there is a small risk that it can also infect normal cells). Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving OBP-301 with chemotherapy and radiation therapy may work better than standard chemotherapy and radiation therapy in treating patients with esophageal or gastroesophageal cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine if the addition of OBP-301 to chemoradiation with carboplatin/paclitaxel is
      safe.

      SECONDARY OBJECTIVES:

      I. To assess toxicities associated with the addition of OBP-301 to chemoradiation.

      II. To assess the number of clinical complete responses (cCR). III. To assess the number of
      patients alive/without progression (progression-free survival [PFS]) and the number of
      patients alive (overall survival [OS]) at 1 and 2 years.

      EXPLORATORY OBJECTIVE:

      I. To report correlate outcomes - cCR, PFS and OS - with immune and virus-based correlative
      assays.

      OUTLINE:

      This study will evaluate an initial dose of OBP-301 and a de-escalated dose, if needed.

      Patients receive OBP-301 by intratumoral injection via endoscopy on days -3, 12, and 26.
      Patients also receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over
      60 minutes on days 1, 8, 15, 22, and 29, and undergo radiation therapy on Monday through
      Friday beginning day 1 for 28 fractions over 5.5 weeks. All treatment continues in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 1 and 6-8 weeks, then every
      3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (OBP-301, carboplatin, paclitaxel, radiation)ExperimentalPatients receive OBP-301 by intratumoral injection on days -3, 12, and 26. Patients also receive carboplatin IV over 30 minutes and paclitaxel IV over 60 minutes on days 1, 8, 15, 22, and 29, and undergo radiation therapy on Monday through Friday beginning day 1 for 28 fractions over 5.5 weeks. All treatment continues in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Paclitaxel
  • Telomerase-specific Type 5 Adenovirus OBP-301

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of
             the esophagus or gastroesophageal junction (GEJ) within 90 days prior to registration

               -  Gastroesophageal junction tumors must be Siewert type I/II

          -  Required diagnostic workup for study entry:

               -  History/physical examination prior to registration

               -  Computed tomography (CT) of the chest/abdomen with intravenous contrast within 28
                  days prior to registration; If CT contrast is contraindicated magnetic resonance
                  imaging (MRI) of the chest/abdomen without contrast is permitted

               -  Endoscopic ultrasound (if technically feasible) within 90 days prior to
                  registration

               -  Whole body positron emission tomography (PET)/CT scan within 42 days prior to
                  registration: Note: scan will be used for radiation treatment planning, in
                  addition to ruling out metastatic disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 days
             prior to registration

          -  White blood cell (WBC) ≥ 3,000/mcL (within 14 days prior to registration)

          -  Absolute neutrophil count ≥ 1,500/mcL (within 14 days prior to registration)

          -  Hemoglobin ≥ 9 gm/dL (within 14 days prior to registration)

          -  Platelets ≥ 100,000/mcL (within 14 days prior to registration)

          -  Creatinine clearance of ≥ 50 ml/min (as calculated by Cockcroft-Gault equation)
             (within 14 days prior to registration)

          -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 14 days prior to
             registration)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN (within 14
             days prior to registration)

          -  Patients must, in the opinion of a thoracic surgeon and/or multidisciplinary team, not
             be a candidate for surgery but are candidates for chemoradiation

          -  Patients must, in the opinion of a treating gastroenterologist, have a tumor that is
             amenable to intratumoral injection with at least 1 mL (1 x 10^12 vp/mL) of OBP-301 and
             be a candidate for 3 endoscopy procedures

          -  Female patients of child bearing potential must have a negative serum/urine pregnancy
             test within 14 days prior to study entry. A female not of childbearing potential is
             one who has undergone a hysterectomy, bilateral oophorectomy, tubal ligation, or who
             has had no menses for 12 consecutive months

          -  Patients of reproductive potential must agree to use effective contraception for the
             duration of study treatment as well as 6 months (for women) or 12 months (for men)
             after the last administered injection of OBP-301. Effective contraception includes
             oral contraceptives, implantable hormonal contraception, double-barrier method or
             intrauterine device

          -  The patient or a legally authorized representative must provide study-specific
             informed consent prior to study entry

          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial

          -  Known acute or chronic hepatitis B or C infection (testing not required prior to study
             entry in patients with no known history of hepatitis B or C)

               -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
                  viral load must be undetectable on suppressive therapy, if indicated

               -  For patients with a history of hepatitis C virus (HCV) infection, they must (i)
                  have been treated and cured, (ii) for patients with HCV infection who are
                  currently on treatment, they are eligible if they have an undetectable HCV viral
                  load

          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months prior to study entry are eligible
             for this trial

        Exclusion Criteria:

          -  Definitive clinical or radiologic evidence of metastatic disease including:

               -  Positive malignant cytology of the pleura, pericardium or peritoneum

               -  Radiographic evidence of involvement of any adjacent mediastinal structure, e.g.
                  aorta, trachea, which would increase the risk of repeated endoscopic
                  interventions

               -  Radiographic evidence of distant organ involvement

               -  Non-regional lymph nodes that cannot be contained within a radiation field

          -  More than 1 esophageal lesion

          -  Prior systemic chemotherapy for the study cancer

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields

          -  Biopsy-proven tumor invasion of the tracheobronchial tree or presence of
             tracheoesophageal fistula or recurrent laryngeal or phrenic nerve paralysis

          -  For patients with known history or current symptoms of cardiac disease, or history of
             treatment with cardiotoxic agents, a New York Heart Association functional
             classification 2C or worse

          -  Uncontrolled diabetes

          -  Infection requiring IV antibiotics at the time of registration

          -  Patients requiring immunosuppressive medications including chronic suppressive steroid
             therapy (greater than the equivalent of 20 mg/day of prednisone), methotrexate,
             azathioprine and TNF-alpha blockers within 7 days prior to study entry

          -  Received live vaccine within 30 days prior to registration

          -  Received a blood transfusion, hematopoietic agent; granulocyte-colony stimulating
             factor (G-CSF), and/or oxygen supplementation within 7 days before the screening lab

          -  Breast feeding females
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:From start of protocol treatment until 30 days after the completion of chemoradiation
Safety Issue:
Description:All adverse events will be graded according to Common Terminology Criteria for Adverse Events version 5.0

Secondary Outcome Measures

Measure:Incidence of Adverse Events
Time Frame:Up to 2 years
Safety Issue:
Description:Assessed using Common Terminology Criteria for Adverse Events version 5.0. Counts of all adverse events (AEs) by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm and within the subset of AEs related to treatment. No formal statistical testing will be performed on these summary data.
Measure:Clinical Complete Response (cCR)
Time Frame:6-8 weeks after completion of chemoradiation
Safety Issue:
Description:If one of the OBP-301 regimens is declared to be safe, the number of cCRs will be reported. No formal statistical testing will be performed on these summary data.
Measure:Progression-free Survival
Time Frame:Time from registration to progressive disease or death, whichever occurs first, assessed up to 2 years
Safety Issue:
Description:If one of the OBP-301 regimens is declared to be safe, number of patients alive without progression will be reported. No formal statistical testing will be performed on these summary data.
Measure:Overall Survival
Time Frame:Time from registration to death, assessed up to 2 years
Safety Issue:
Description:If one of the OBP-301 regimens is declared to be safe, number of patients alive will be reported. No formal statistical testing will be performed on these summary data.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NRG Oncology

Trial Keywords

  • OBP-301
  • viral therapy

Last Updated

September 14, 2020