Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04391049
Recruitment Status : Recruiting
First Posted : May 18, 2020
Last Update Posted : December 9, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: Carboplatin Drug: Paclitaxel Radiation: Radiation Therapy Biological: Telomerase-specific Type 5 Adenovirus OBP-301 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 29, 2020
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (OBP-301, carboplatin, paclitaxel, radiation)
Patients 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.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiation
  • Radiation Therapy, NOS
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

Biological: Telomerase-specific Type 5 Adenovirus OBP-301
Given by intratumoral injection
Other Names:
  • OBP-301
  • Telomelysin ™




Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: From start of protocol treatment until 30 days after the completion of chemoradiation ]
    All adverse events will be graded according to Common Terminology Criteria for Adverse Events version 5.0


Secondary Outcome Measures :
  1. Incidence of Adverse Events [ Time Frame: Up to 2 years ]
    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.

  2. Clinical Complete Response (cCR) [ Time Frame: 6-8 weeks after completion of chemoradiation ]
    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.

  3. Progression-free Survival [ Time Frame: Time from registration to progressive disease or death, whichever occurs first, assessed up to 2 years ]
    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.

  4. Overall Survival [ Time Frame: Time from registration to death, assessed up to 2 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT04391049


Locations
Layout table for location information
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Site Public Contact    212-639-7592      
Principal Investigator: Geoffrey Y. Ku         
Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Geoffrey Y Ku NRG Oncology
Layout table for additonal information
Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT04391049    
Other Study ID Numbers: NRG-GI007
NCI-2020-02320 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GI007 ( Other Identifier: NRG Oncology )
NRG-GI007 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: May 18, 2020    Key Record Dates
Last Update Posted: December 9, 2020
Last Verified: December 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by NRG Oncology:
OBP-301
viral therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Paclitaxel
Carboplatin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action