Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02535312
Recruitment Status : Active, not recruiting
First Posted : August 28, 2015
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE August 27, 2015
First Posted Date  ICMJE August 28, 2015
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE August 11, 2015
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
  • Dose-limiting toxicity (Arm A) [ Time Frame: 21 days ]
    Dose-limiting toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 as of April 1, 2018).
  • Response rate (Arm B) [ Time Frame: Up to 8 weeks post-treatment ]
    Will be measured using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
  • Dose-limiting toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Arm A) [ Time Frame: 21 days ]
  • Response rate using RECIST (Arm B) [ Time Frame: Up to 8 weeks post-treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
  • Pharmacokinetic (PK) parameter [ Time Frame: Pre-methoxyamine and cisplatin, and at 15 and 30 minutes, 1, 2, 4, 6, and 24 hours post cisplatin on course 1 ]
    Individual PK parameter estimates (e.g., maximum C concentration observed, volume in steady state, systemic clearance, half-life, and area under the curve) will be determined for methoxyamine and cisplatin for each patient and tabulated using summary statistics (means and coefficients of variation).
  • Establishment of pleural and peritoneal effluent-derived cell lines [ Time Frame: Baseline ]
    Feasibility of establishing pleural and peritoneal effluent-derived cell lines will be reflected in the number successfully established.
  • Response of cultured pleural and peritoneal mesothelioma cells to cisplatin, pemetrexed, and methoxyamine [ Time Frame: Baseline ]
    Results will be compared to patients' responses. Will be studied using standard experimental design approaches and generalized linear model analyses.
  • Objective clinical response [ Time Frame: Up to 8 weeks post-treatment ]
    RECIST-defined responses will be summarized as a fraction of all subjects, and as a fraction of all subjects in Arm B, using exact binomial 9 percent confidence intervals.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2015)
  • Establishment of pleural and peritoneal effluent-derived cell lines [ Time Frame: Baseline ]
    Feasibility of establishing pleural and peritoneal effluent-derived cell lines will be reflected in the number successfully established.
  • Objective clinical response [ Time Frame: Up to 8 weeks post-treatment ]
    RECIST-defined responses will be summarized as a fraction of all subjects, and as a fraction of all subjects in the Arm A or Arm B expansion cohorts, using exact binomial 9 percent confidence intervals.
  • Pharmacokinetic (PK) parameter [ Time Frame: Pre-methoxyamine and cisplatin, and at 30 minutes, 1, 2, 4, 6, 24, and 167 hours post cisplatin on course 1 ]
    PK data analyses will be performed using non-compartmental methods according to the rule of linear trapezoids. Individual PK parameter estimates (e.g., maximum C concentration observed, volume in steady state, systemic clearance, half-life, and area under the curve) will be determined for methoxyamine and cisplatin for each patient and tabulated using summary statistics (means and coefficients of variation).
  • Response of cultured pleural and peritoneal mesothelioma cells to cisplatin, pemetrexed, and methoxyamine [ Time Frame: Baseline ]
    Results will be compared to patients' responses. Will be studied using standard experimental design approaches and generalized linear model analyses.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE Phase I Study of TRC102 in Combination With Cisplatin and Pemetrexed in Patients With Advanced Solid Tumors / Phase II Study of TRC102 With Pemetrexed in Patients Refractory to Pemetrexed and Cisplatin or Carboplatin
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.
Detailed Description

PRIMARY OBJECTIVES:

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Malignant Solid Neoplasm
  • Advanced Peritoneal Malignant Mesothelioma
  • Advanced Pleural Malignant Mesothelioma
  • Recurrent Peritoneal Malignant Mesothelioma
  • Recurrent Pleural Malignant Mesothelioma
  • Refractory Malignant Solid Neoplasm
  • Unresectable Solid Neoplasm
Intervention  ICMJE
  • 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
  • Drug: Methoxyamine
    Given PO
    Other Name: TRC102 Base
  • Drug: Pemetrexed Disodium
    Given IV
    Other Names:
    • 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
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Cisplatin
    • Drug: Methoxyamine
    • Drug: Pemetrexed Disodium
  • Experimental: 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.
    Interventions:
    • Drug: Methoxyamine
    • Drug: Pemetrexed Disodium
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 27, 2015)
58
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02535312
Other Study ID Numbers  ICMJE NCI-2015-00127
NCI-2015-00127 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PHI-76
9837 ( Other Identifier: City of Hope Comprehensive Cancer Center LAO )
9837 ( Other Identifier: CTEP )
UM1CA186689 ( U.S. NIH Grant/Contract )
UM1CA186705 ( U.S. NIH Grant/Contract )
UM1CA186717 ( U.S. NIH Grant/Contract )
ZIABC011078 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marianna Koczywas City of Hope Comprehensive Cancer Center LAO
PRS Account National Cancer Institute (NCI)
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP