Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Pemetrexed Disodium and Cisplatin or Carboplatin
NCT ID: NCT02535312
Last Updated: 2025-10-29
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
30 participants
INTERVENTIONAL
2016-03-08
2026-10-15
Brief Summary
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Detailed Description
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I. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) for the combination of methoxyamine (TRC102) with pemetrexed (pemetrexed disodium) and cisplatin in patients with advanced solid tumors. (Arm A) II. To describe the toxicities of TRC102 combined with pemetrexed and cisplatin at each dose studied. (Arm A) III. To describe responses to the drug combination at each dose level. (Arm A) IV. To detect activity of the combination of TRC102 and pemetrexed, as evidenced by tumor response in patients with advanced malignant mesothelioma previously treated with pemetrexed and cisplatin. (Arm B)
SECONDARY OBJECTIVES:
I. To describe pharmacokinetic parameters of TRC102 given concurrent with pemetrexed and cisplatin.
II. To evaluate the pharmacodynamic parameters of TRC102 given concurrently with pemetrexed and cisplatin.
III. To explore the feasibility of establishing pleural and peritoneal effluent-derived cell lines and to evaluate the response of cultured pleural and peritoneal mesothelioma cells to cisplatin, pemetrexed, and TRC102.
IV. To document all objective clinical responses to TRC102 in combination with pemetrexed and cisplatin.
OUTLINE: This is a phase I, dose-escalation study of methoxyamine, followed by a phase II study. Patients are assigned to 1 of 2 treatment arms.
ARM A: Patients receive methoxyamine orally (PO) once daily (QD) on days 1-4, pemetrexed disodium intravenously (IV) over 10 minutes, and cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician.
ARM B: Patients receive methoxyamine PO QD on days 1-4 and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician.
After completion of study treatment, patients are followed up for 8 weeks.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A (methoxyamine, pemetrexed disodium, cisplatin)
Patients receive methoxyamine PO QD on days 1-4, pemetrexed disodium IV over 10 minutes, and cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician.
Cisplatin
Given IV
Methoxyamine
Given PO
Pemetrexed Disodium
Given IV
Arm B (methoxyamine, pemetrexed disodium)
Patients receive methoxyamine PO QD on days 1-4 and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may continue methoxyamine and pemetrexed disodium beyond cycle 6 if the patient continues to benefit from treatment at the discretion of the treating physician.
Methoxyamine
Given PO
Pemetrexed Disodium
Given IV
Interventions
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Cisplatin
Given IV
Methoxyamine
Given PO
Pemetrexed Disodium
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Arm A dose level 4 (75 mg/m\^2 cisplatin): patients with histologically proven chemotherapy-naive advanced unresectable solid tumors for which pemetrexed combined with cisplatin is an indicated regimen
* Arm B (first stage of phase II of TRC102 and pemetrexed): patients with malignant pleural or peritoneal mesothelioma who had progressed while being treated with or had recurred within 6 months of being treated with pemetrexed and cisplatin or carboplatin frontline; intervening treatment is allowed
* Prior pemetrexed is allowed except Arm A dose level 4 (cisplatin 75 mg/m\^2)
* Eastern Cooperative Oncology Group (ECOG) performance status 0 -1 (Karnofsky \>= 70%)
* Life expectancy of greater than 3 months
* Absolute neutrophil count \>= 1,500/uL
* Platelets \>= 100,000/uL
* Hemoglobin \>= 10.0 g/dl
* Prothrombin time or international normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN)
* Total bilirubin \< 1.5 x ULN
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN or =\< 5 x ULN if metastatic disease involves liver
* Serum creatinine =\< 1.5 x ULN or a calculated creatinine clearance \>= 60 ml/min/1.73 m\^2 (Cockcroft-Gault method) for patients receiving combination of cisplatin and pemetrexed and \>= 45 ml/min/1.73 m\^2 for patients receiving pemetrexed; 24 hour urine for creatinine clearance is acceptable if the calculated creatinine clearance is insufficient
* For patients enrolled in Arm B (first stage of phase II of TRC102 and pemetrexed) measurable disease is required according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for patients with solid tumors and modified RECIST criteria as described by Byrne and Novak for patients with malignant pleural mesothelioma; pleural effusion and ascites are not considered measurable disease
* Patients must be able to swallow whole capsules; nasogastric or gastrointestinal (G)-tube administration is not allowed
* The effects of TRC102 on the developing human fetus are unknown; for this reason and because TRC102 as well as other therapeutic agents used in this trial are known to be teratogenic, 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 4 months after completion of the study drugs; 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 4 months after completion of TRC102, pemetrexed and cisplatin administration; non-childbearing potential is defined as (by other than medical reasons): \>= 45 years of age and has not had menses for \>= 2 years, amenorrheic for \< 2 years without hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation, or post hysterectomy, oophorectomy or tubal ligation; documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by ultrasound; tubal ligation must be confirmed with medical records of the actual procedure otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit though 4 months after the last dose of study drugs
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
* Patients who are receiving any other investigational agents
* Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial; patients with treated brain metastases, whose brain metastatic disease has remained stable for greater than or equal to 4 weeks without requiring steroid and anti-seizure medications are eligible to participate
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TRC102 or pemetrexed and cisplatin
* No studies have been performed to assess potential metabolic and transport interactions of TRC102; 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; the case report form must capture the concurrent use of all other drugs, over-the-counter medications, or alternative therapies
* 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 because TRC102 is agent 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, breastfeeding should be discontinued if the mother is treated with TRC102; these potential risks may also apply to other agents used in this study
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with TRC102; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
* Patients with known disorders associated with hemolysis
* Patients with thromboembolic disease and on anticoagulation
* Patients with a prior cumulative cisplatin dose \> 300 mg/m\^2 (pertains to Arm A only)
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Marianna Koczywas
Role: PRINCIPAL_INVESTIGATOR
City of Hope Comprehensive Cancer Center LAO
Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Keck Medical Center of USC Pasadena
Pasadena, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2015-00127
Identifier Type: REGISTRY
Identifier Source: secondary_id
PHI-76
Identifier Type: -
Identifier Source: secondary_id
9837
Identifier Type: OTHER
Identifier Source: secondary_id
9837
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2015-00127
Identifier Type: -
Identifier Source: org_study_id
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