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 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 3 other identifiers: NRG-GI007NCI-2020-02320U10CA180868
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 17

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.

Conditions

Advanced Esophageal Adenocarcinoma; Clinical Stage II 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 IIA Esophageal Adenocarcinoma AJCC v8; Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIB 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; Squamous Cell Cancer; Advanced Gastroesophageal Junction Adenocarcinoma; Clinical Stage II Esophageal 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; Pathologic Stage II Gastroesophageal Junction 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; Squamous Cell Carcinoma

Keywords

OBP-301; viral therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Any Dose-Limiting Toxicities (DLTs)

  Adverse events are graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, which grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. A DLT is defined as the following that are definitely or probably attributed to OBP-301: * Any grade ≥3 adverse event EXCEPT for the following: * Grade 3 nausea/vomiting * Grade 3 esophagitis or dehydration * The first occurrence of grade 3/4 neutropenia * Grade 3/4 lymphopenia (since this is a known toxicity of chemoradiation and OBP-301) * Any toxicity that leads to a \>14-day cumulative delay in chemoradiation. If 0 or 1 participants of 6 participants experienced a DLT, then the treatment regimen would be considered safe (and 9 more would be accrued for secondary endpoints). Otherwise, the regimen would be deemed too toxic and a second cohort of six participants would be accrued to a lower dose of OBP-301 (1 x 10\^11 vp/mL).

  From start of protocol treatment until 30 days after the completion of chemoradiation, approximately 10 weeks.

Secondary Outcomes (4)

• Number of Participants by Highest Grade Adverse Event Reported

  From start of protocol treatment to last follow-up. Maximum follow-up was 28.7 months.

• Number of Participants With Clinical Complete Response (cCR)

  6-8 weeks after completion of chemoradiation, approximately 11.5-13.5 weeks from baseline.

• Number of Participants Alive Without Progression at 1 and 2 Years

  At 1 and 2 years

• Number of Participants Alive at 1 and 2 Years

  At 1 and 2 years

Study Arms (1)

Treatment (OBP-301, carboplatin, paclitaxel, radiation)

EXPERIMENTAL

Patients receive OBP-301 (1×10\^12 vp/mL) by intra-tumoral injection via endoscopy on days -3, 12, and 26. Patients also receive paclitaxel IV (50 mg/m\^2) over 60 minutes followed by carboplatin IV (AUC 2) over 30 minutes and on days 1, 8, 15, 22, and 29, and undergo radiation therapy (1.8 Gy/faction) on Monday through Friday beginning day 1 for 28 fractions (50.4 Gy total) over 5.5 weeks. All treatment continues in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy; Biological: Telomerase-specific Type 5 Adenovirus OBP-301

Interventions

Carboplatin DRUG

Intravenously (IV)

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (OBP-301, carboplatin, paclitaxel, radiation)

Paclitaxel DRUG

Intravenously (IV)

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (OBP-301, carboplatin, paclitaxel, radiation)

Radiation Therapy RADIATION

Daily fractions

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, RADIOTHERAPY, RT, Therapy, Radiation

Treatment (OBP-301, carboplatin, paclitaxel, radiation)

Telomerase-specific Type 5 Adenovirus OBP-301 BIOLOGICAL

Intra-tumoral injection

Also known as: OBP-301, Telomelysin ™

Treatment (OBP-301, carboplatin, paclitaxel, radiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma or squamous cell carcinoma (SCC) 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
• Bronchoscopy for squamous cell carcinoma (SCC) tumors that are adjacent to the airway to exclude a tracheoesophageal fistula within 42 days prior to registration
• 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 0-2 within 14 days prior to registration
• Adequate hematologic function within 14 days prior to registration defined as follows 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)
• Adequate renal function within 14 days prior to registration defined as follows 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)
• AST/ALT ≤ 2.5 x ULN
• Patients for whom non-operative management is a viable option in the opinion of a thoracic surgeon and/or multidisciplinary team and are candidates for chemoradiation; this does not preclude patients from receiving surgery after chemoradiation if felt to me medically indicated;
• 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

You may not qualify if:

• 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
• Tracheoesophageal fistula
• 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

Sponsors & Collaborators

• NRG Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (17)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

City of Hope Upland

Upland, California, 91786, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Neoplasms, Squamous Cell

Interventions

Carboplatin; Paclitaxel; Taxes; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

215-574-3208

Study Officials

• Geoffrey Y Ku

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 18, 2020
• Study Start: December 2, 2021
• Primary Completion: October 6, 2024
• Study Completion (Estimated): October 1, 2026
• Last Updated: January 30, 2026
• Results First Posted: May 29, 2025

Record last verified: 2026-01

Locations

US (17)