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Trial record 1 of 1 for:    NCT02535325
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Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

This study is currently recruiting participants.
See Contacts and Locations
Verified May 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02535325
First received: August 27, 2015
Last updated: June 26, 2017
Last verified: May 2017
  Purpose
This phase I trial studies the side effects and best dose of methoxyamine when given together with pemetrexed disodium, cisplatin, and radiation therapy in treating patients with stage IIIA-IV non-small cell lung cancer. Drugs used in chemotherapy, such as methoxyamine, pemetrexed disodium, and cisplatin, 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 methoxyamine together with pemetrexed disodium, cisplatin, and radiation therapy may kill more tumor cells.

Condition Intervention Phase
Metastatic Malignant Neoplasm in the Brain Stage IIIA Large Cell Lung Carcinoma Stage IIIA Lung Adenocarcinoma Stage IIIA Non-Small Cell Lung Cancer Stage IIIB Large Cell Lung Carcinoma Stage IIIB Lung Adenocarcinoma Stage IIIB Non-Small Cell Lung Cancer Stage IV Large Cell Lung Carcinoma Stage IV Lung Adenocarcinoma Stage IV Non-Small Cell Lung Cancer Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Cisplatin Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Drug: Methoxyamine Drug: Pemetrexed Disodium Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I Study of Methoxyamine Combined With Chemo-radiation for Locally Advanced Non-squamous Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Incidence of toxicity of the combination therapy, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 6 months ]
    Toxicity data will be tabulated.

  • MTD of methoxyamine in combination with pemetrexed disodium, cisplatin and RT, graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 21 days ]
    MTD is defined as the highest dose level in which 0/6 or 1/6 patients suffer dose-limiting toxicity.


Secondary Outcome Measures:
  • Change in lab correlative expression levels (including UNG, TS, ERCC1, Ki-67 and TopoII-alpha) [ Time Frame: Baseline to up to 6 months ]
    The change of lab correlatives measured at baseline and post-treatment will be compared by paired T-test for interval scale measure and McNemar test for nominal measure.

  • Disease-free survival [ Time Frame: Up to 6 months ]
    Disease-free survival is analyzed using the Kaplan-Meier method. Factors, such as age, gender, baseline histology and lab correlates including UNG, TS, ERCC1, Ki-67 and TopoII-alpha that predict survival will be identified by Cox model or extended Cox model.

  • Progression-free survival (PFS) [ Time Frame: At 6 months ]
    PFS is analyzed using the Kaplan-Meier method. Factors, such as age, gender, baseline histology and lab correlates including uracil deoxyribonucleic acid (DNA) N-glycosylase (UNG), thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), Ki-67 and Topoisomerase II-alpha (TopoII-alpha) that predict survival will be identified by Cox model or extended Cox model.

  • Response rate (clinical/tumor response) [ Time Frame: Up to 6 months ]
    The true response rate of the combination therapy for this patient population will be estimated based on the number of responses using a binomial distribution and its confidence intervals will be estimated using Wilson's method. The factors that predict the response will be identified by logistic regression.


Estimated Enrollment: 15
Actual Study Start Date: September 30, 2015
Estimated Primary Completion Date: October 1, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pemetrexed, methoxyamine, cisplatin, RT)

COURSES 1-2: Patients receive pemetrexed disodium IV over 10 minutes and methoxyamine PO day 1; and cisplatin IV over 0.5-24 hours on day 3. Patients also undergo 3-D conformal RT or IMRT QD 5 days a week (3 days of week 1 and 4 days of week 4) for 30 fractions total.

COURSES 3-4: Beginning at least 10 days after RT completion, patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 0.5-24 hours on day 1.

Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo 3-D conformal RT
Other Names:
  • 3-dimensional radiation therapy
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Methoxyamine
Given PO
Other Name: TRC102
Drug: Pemetrexed Disodium
Given IV
Other Names:
  • Alimta
  • LY231514
  • N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of methoxyamine (TRC102) in combination with pemetrexed (pemetrexed disodium)-cisplatin and thoracic radiotherapy.

SECONDARY OBJECTIVES:

I. To (descriptively) assess the toxicity profile of methoxyamine (TRC102) in combination with pemetrexed-cisplatin and thoracic radiotherapy.

II. To (descriptively) assess the short-term progression-free survival at 6 months (PFS6) in the patients treated on this protocol.

III. To observe and record anti-tumor activity.

OUTLINE: This is a dose-escalation study of methoxyamine.

COURSES 1-2: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes and methoxyamine orally (PO) day 1; and cisplatin IV over 0.5-24 hours on day 3. Patients also undergo 3-dimensional (3-D) conformal radiation therapy (RT) or intensity-modulated radiation therapy (IMRT) once daily (QD) 5 days a week (3 days of week 1 and 4 days of week 4) for 30 fractions total.

COURSES 3-4: Beginning at least 10 days after RT completion, patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 0.5-24 hours on day 1.

Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 weeks and then every 3 months for 6 months.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have pathologic diagnosis of adenocarcinoma or large cell carcinoma of the lung with confirmation by immunohistochemistry (e.g., transcription termination factor 1 [TTF-1] positivity) (histologic tissue diagnosis is recommended, but cytology is acceptable); stage IIIA/IIIB or oligometastatic stage IV in which the patient is still considered an appropriate candidate for aggressive chemoradiotherapy for the primary tumor; oligometastatic disease is defined as =< 5 metastatic sites (=< 3 lesions per organ); for intracranial metastasis, the patient should have asymptomatic disease that is stable on steroids or 1 to 3 symptomatic metastatic lesions treated with stereotactic radiosurgery (SRS)
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2
  • Life expectancy of greater than 12 months
  • Ability to swallow and retain orally-administered medication and does not have any clinically significant gastro-intestinal abnormalities (e.g., malabsorption syndrome or major resection of the stomach or bowel)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 × institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
  • Creatinine within normal institutional limits OR
  • Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Hemoglobin >= 9 g/dL without transfusion within 7 days prior to enrollment
  • 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 and for the duration of study participation; 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 and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of methoxyamine administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had prior chemotherapy or any other investigational drug within 30 days of registration or prior radiotherapy to the study treatment volume; prior surgery is allowed; there must be at least 6 weeks between mitomycin or nitrosoureas and any new therapy
  • Patients who are receiving any other investigational agents
  • Patients with a history of any active malignancy requiring on-going treatment, except basal cell carcinoma or squamous cell carcinoma of the skin
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to methoxyamine or to pemetrexed or cisplatin
  • Undetectable haptoglobin or evidence of glucose-6-phophate dehydrogenase (G6PD) deficiency, pyruvate kinase deficiency, hemoglobinopathy, hereditary spherocytosis, thalassemia or other disorder associated with hemolysis
  • Patients receiving any medications or substances that are inhibitors or inducers of nonsteroidal anti-inflammatory drugs (NSAIDS), probenecid, salisylates, sulfonamides are ineligible; concomitant drugs that are sensitive cytochrome P450 (CYP450) substrates or strong and moderate CYP450 inducers and inhibitors should be avoided; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with methoxyamine
  • Patients who are known to be human immunodeficiency positive (HIV)-positive and are on combination antiretroviral therapy are ineligible
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02535325

Locations
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Tithi Biswas    800-641-2422      
Principal Investigator: Tithi Biswas         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Tithi Biswas Case Western Reserve University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02535325     History of Changes
Other Study ID Numbers: NCI-2015-01408
NCI-2015-01408 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA204397
CASE 5514
CASE 5514 ( Other Identifier: Case Western Reserve University )
9834 ( Other Identifier: CTEP )
P30CA043703 ( US NIH Grant/Contract Award Number )
Study First Received: August 27, 2015
Last Updated: June 26, 2017

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Neoplasms
Neoplasms, Second Primary
Brain Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cisplatin
Pemetrexed
Succinylcholine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Neuromuscular Depolarizing Agents

ClinicalTrials.gov processed this record on June 27, 2017