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

NCT02535312 | Active Not Recruiting Phase 1 Results

• 7 other identifiers: NCI-2015-00127PHI-769837UM1CA186689UM1CA186705UM1CA186717ZIABC011078
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 14

Brief Summary

This phase I/II trial studies the side effects and the best dose of methoxyamine when given together with cisplatin and pemetrexed disodium and to see how well it works in treating patients with solid tumors or mesothelioma that have spread to other places in the body and usually cannot be cured or controlled with standard treatment (advanced), or mesothelioma that does not respond to pemetrexed disodium and cisplatin or carboplatin (refractory). Methoxyamine may shrink the tumor and may also help cisplatin and pemetrexed disodium work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as cisplatin and pemetrexed disodium, 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. Giving methoxyamine together with cisplatin and pemetrexed disodium may be a better treatment for solid tumors or mesothelioma than methoxyamine and pemetrexed disodium.

Conditions

Unresectable Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Malignant Solid Neoplasm; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Refractory Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (3)

• Number of Participants With at Least One Dose Limiting Toxicity (DLT) - Phase I

  Dose-limiting toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Pre-specified DLT criteria included the following adverse events (AE), judged to be at least possibly related to study therapy: grade 3 or greater non-hematologic toxicity, grade 3 thrombocytopenia with bleeding, any grade 4 thrombocytopenia, grade 4 febrile neutropenia lasting \> 7 day, any grade febrile neutropenia, any grade 5 toxicity. Treatment delay of cycle 2 by more than 2 weeks and inability to administer 3 of the 4 doses due to toxicity in the first treatment course were also considered DLTs. Controllable nausea, vomiting and diarrhea, electrolyte toxicities correctable (to baseline or grade 1) with repletion and grade 3 creatinine elevation correctable (to grade 1 or less) with IV hydration were not considered DLT's.

  During the first cycle of treatment, up to 21 days

• Maximum Tolerated Dose (MTD)

  The maximum tolerated dose of TRC102 in combination with 500mg/m\^2 IV of Pemetrex and 60 or 75 mg/m\^2 IV of Cisplatin is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.

  21 days from start of treatment, up to 2 years

• Number of Subject With Overall Response

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; Partial Response (PR), at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Overall Response (OR) = CR + PR

  Up to 8 weeks post-treatment

Secondary Outcomes (2)

• Progression-free Survival

  From start of treatment to time of progression or death from any cause, whichever occurs first, assessed up to at least 1 year

• Overall Survival

  From start of treatment to time of death from any cause, assessed up to at least 3 years

Study Arms (2)

Arm A (methoxyamine, pemetrexed disodium, cisplatin)

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Methoxyamine; Drug: Pemetrexed Disodium

Arm B (methoxyamine, pemetrexed disodium)

EXPERIMENTAL

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.

Drug: Methoxyamine; Drug: Pemetrexed Disodium

Interventions

Pemetrexed Disodium DRUG

Given IV

Also known as: Alimta, Almita, 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

Arm A (methoxyamine, pemetrexed disodium, cisplatin); Arm B (methoxyamine, pemetrexed disodium)

Cisplatin DRUG

Given IV

Also known as: 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

Arm A (methoxyamine, pemetrexed disodium, cisplatin)

Methoxyamine DRUG

Given PO

Also known as: TRC102 Base

Arm A (methoxyamine, pemetrexed disodium, cisplatin); Arm B (methoxyamine, pemetrexed disodium)

Eligibility Criteria

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

You may qualify if:

• Arm A dose escalation: patients with histologically or cytologically proven advanced solid tumors for which standard treatments are not available, or for whom the current dose level of cisplatin in combination with pemetrexed is appropriate; =\< 2 prior cytotoxic chemotherapy regimen
• 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

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have had targeted therapy will be required to wait 2 weeks due to short half-life of the drugs; treatment with bisphosphonates is permitted
• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt Breast Center at One Hundred Oaks

Nashville, Tennessee, 37204, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; methoxyamine; Pemetrexed

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Marianna Koczywas

  City of Hope Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: August 28, 2015
• Study Start: March 8, 2016
• Primary Completion: December 31, 2022
• Study Completion (Estimated): October 15, 2026
• Last Updated: April 17, 2026
• Results First Posted: April 25, 2024

Record last verified: 2026-04

Locations

US (14)