Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer
A Phase 2 Randomized Study of the BER Inhibitor TRC102 in Combination With Standard Pemetrexed-Platinum-Radiation in Stage III Non-Squamous Non-Small Cell Lung Cancer
4 other identifiers
interventional
42
1 country
34
Brief Summary
This phase II trial tests whether TRC102 (methoxyamine hydrochloride) in combination usual care treatment comprised of pemetrexed, cisplatin or carboplatin, and radiation therapy followed by durvalumab works better than the usual care treatment alone to shrink tumors in patients with stage III non-squamous non-small cell lung cancer (NSCLC). TRC102 is in a class of drugs called antineoplastic agents. It blocks the ability of a cell to repair damage to its deoxyribonucleic acid (DNA) and may kill tumor cells. It may also help some anticancer drugs work better. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy sources to kill tumor cells and shrink tumors. Giving TRC102 in combination with usual care treatment may be more effective than usual care treatment alone in stabilizing and lengthening survival time in patients with stage III non-squamous NSCLC.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Dec 2022
Typical duration for phase_2
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 14, 2022
CompletedFirst Posted
Study publicly available on registry
January 20, 2022
CompletedStudy Start
First participant enrolled
December 15, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
June 11, 2026
June 1, 2026
4.5 years
January 14, 2022
June 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS)
PFS primary analysis will be performed using a stratified log-rank test (with the strata being the same as the randomization strata) with a one-sided significance level of 0.10.
From randomization to the date of the first documented event of tumor progression or death in the absence of disease progression, assessed at 12 months from randomization and up to 5 years
Secondary Outcomes (2)
Overall survival (OS)
From randomization until death from any cause, assessed up to 5 years
Incidence of grade 3 or higher adverse events
Up to 1 year
Study Arms (2)
Arm I (methoxyamine, usual care)
EXPERIMENTALPatients receive methoxyamine PO on day 1 of each cycle, pemetrexed IV over 10 minutes on day 1 of each cycle, and cisplatin IV over 60 minutes or carboplatin IV over 30 minutes on day 3 of each cycle. Beginning day 3, patients also undergo radiation therapy daily Monday-Friday. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after cycle 2, patients receive durvalumab IV over 60 minutes every 2 weeks or monthly for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial and FDG-PET/CT scan during screening and optionally on study.
Arm II (usual care)
ACTIVE COMPARATORPatients receive pemetrexed IV over 10 minutes and cisplatin IV over 60 minutes or carboplatin IV over 30 minutes on day 1 of each cycle. Beginning day 1 of each cycle, patients also undergo radiation therapy daily Monday-Friday. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after cycle 2, patients receive durvalumab IV over 60 minutes every 2 weeks or monthly for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial and FDG-PET/CT scan during screening and optionally on study.
Interventions
Undergo FDG-PET/CT
Undergo thoracic radiation
Given IV
Given IV
Given IV
Given IV
Undergo CT and FDG-PET/CT
Undergo MRI
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed adenocarcinoma or large cell carcinoma of the lung with confirmation by immunohistochemistry (histologic tissue diagnosis is preferred, but cytology is acceptable).
- Patients must have newly staged IIIA, IIIB or IIIC disease according to the 8th tumor, node, metastasis (TNM) staging classification and to be considered appropriate candidates for aggressive chemoradiotherapy.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam.
- Patients must have diagnosed NSCLC, with no prior overlapping radiation therapy delivered for locally advanced NSCLC. Prior stereotactic radiation therapy for stage I lung cancer without overlapping is allowed. Prior systemic antineoplastic therapy is allowed, as deemed appropriate by the treating physician. Prior surgery is allowed. History of previous stage I NSCLC with new mediastinal nodal recurrence (new stage III are eligible).
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of TRC102 in combination with pemetrexed, cisplatin, and durvalumab in patients \< 18 years of age, children are excluded from this study.
- Body weight \> 30 kg with acceptable nutritional status based on evaluation by treating physician.
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%).
- Leukocytes \>= 3,000/mcL.
- Hemoglobin \>= 9.0 g/dL.
- Absolute neutrophil count \>= 1,500/mcL.
- Platelets \>= 150,000/mcL.
- Serum bilirubin within normal institutional limits (0 - 1.2 mg/ dl). (This will not apply to patients with confirmed Gilbert's syndrome \[persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology\], who will be allowed only in consultation with their physician.).
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 x institutional upper limit of normal (=\< 39 U/L).
- Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal (=\< 52 U/L).
- Creatinine =\< 1.3 mg/dL.
- +19 more criteria
You may not qualify if:
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia.
- Patients who are receiving any other investigational agents.
- Patients with treated brain metastases are not eligible as the study is for stage III disease only.
- Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are not eligible as the study includes only stage III disease.
- Patients with EGFR or ALK mutations are ineligible.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC102 or other agents used in study.
- Patients with uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent.
- Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because TRC102 is a biochemical inhibitor of the BER pathway and durvalumab is an anti-PDL1 antibody, agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TRC102 or durvalumab, breastfeeding should be discontinued if the mother is treated with TRC102 or durvalumab. These potential risks may also apply to other agents used in this study.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after durvalumab monotherapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of durvalumab.
- Patients with active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia.
- Patients with hypothyroidism (e.g. following Hashimoto thyroiditis) stable on hormone replacement.
- Any chronic skin condition that does not require systemic therapy.
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (34)
Keck Medicine of USC Buena Park
Buena Park, California, 90621, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
City of Hope at Irvine Lennar
Irvine, California, 92618, United States
City of Hope Antelope Valley
Lancaster, California, 93534, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, 92663, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
City of Hope Upland
Upland, California, 91786, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
UChicago Medicine Northwest Indiana
Crown Point, Indiana, 46307, United States
Jersey City Medical Center
Jersey City, New Jersey, 07302, United States
Saint Barnabas Medical Center
Livingston, New Jersey, 07039, United States
Monmouth Medical Center
Long Branch, New Jersey, 07740, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
Robert Wood Johnson University Hospital Somerset
Somerville, New Jersey, 08876, United States
Community Medical Center
Toms River, New Jersey, 08755, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Texas Medical Branch
Galveston, Texas, 77555-0565, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Afshin Dowlati
Case Western Reserve University
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 14, 2022
First Posted
January 20, 2022
Study Start
December 15, 2022
Primary Completion (Estimated)
June 30, 2027
Study Completion (Estimated)
June 30, 2027
Last Updated
June 11, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.