Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02611024
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : December 23, 2019
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Tracking Information
First Submitted Date  ICMJE November 5, 2015
First Posted Date  ICMJE November 20, 2015
Last Update Posted Date December 23, 2019
Actual Study Start Date  ICMJE May 6, 2016
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 28, 2017)
  • Maximum Tolerated Dose (MTD) [ Time Frame: 48 months ]
    The MTD for each group will be the lowest dose level explored during dose escalation which one third or more of evaluable patients develops DLT in Cycle 1.
  • Recommended Dose (RD) [ Time Frame: 48 months ]
    The RD for each groupwill be the highest dose level explored during dose escalation in which fewer than one third of evaluable patients develop DLT during Cycle 1.
Original Primary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
  • Maximum Tolerated Dose (MTD) [ Time Frame: 36 months ]
    The MTD will be the lowest dose level explored during dose escalation which one third or more of evaluable patients develops DLT in Cycle 1.
  • Recommended Dose (RD) [ Time Frame: 36 months ]
    The RD will be the highest dose level explored during dose escalation in which fewer than one third of evaluable patients develop DLT during Cycle 1.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2019)
  • Safety evaluation [ Time Frame: Since start of the treatment until 30 days after the last administration of study treatment; or until start of a new antitumor therapy or death ]
    AEs will be graded according to the NCI-CTCAE v.4.
  • Peak Plasma Concentration (Cmax) [ Time Frame: 48 months ]
    Pharmacokinetic Outcome Measures
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: 48 months ]
    Pharmacokinetic Outcome Measures
  • Volume of distribution based on the terminal half-life (Vz) [ Time Frame: 48 months ]
    Pharmacokinetic Outcome Measures
  • Volume of distribution at steady state (Vss) [ Time Frame: 48 months ]
    Pharmacokinetic Outcome Measures
  • Clearance (CL) [ Time Frame: 48 months ]
    Pharmacokinetic Outcome Measures
  • Half-life (t1/2) [ Time Frame: 48 months ]
    Pharmacokinetic Outcome Measures
  • Evaluation of antitumor response [ Time Frame: Start treatment until PD, other antitumor therapy, death or until 12 months after the inclusion of the last evaluable patient in the study (end of study), whichever occurs first. ]
    Evaluable and measurable as per RECIST v.1.1 or RANO for Gliobastoma patients
  • Progression-free Survival [ Time Frame: From the date of first infusion of study treatment to the date of progression or death or until 12 months after the inclusion of the last evaluable patient in the study (end of study), whichever occurs first. ]
    Time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death has not occurred at the time of the analysis, the PFS will be censored on the date of last tumor evaluation.
  • Overall Survival [ Time Frame: From the date of first infusion of study treatment to the date or death or until 12 months after the inclusion of the last evaluable patient in the study (end of study), whichever occurs first. ]
    Time from the date of first infusion of study treatment to the date of death (due to any cause). Patients with no documented death will be censored at the last date they are known to be alive.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2015)
  • AUC (area under the curve) [ Time Frame: 36 months ]
  • Clearance [ Time Frame: 36 months ]
  • Characterisation of Cmax (maximum concentration) [ Time Frame: 36 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors
Official Title  ICMJE Phase I, Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Pretreated Patients With Selected Advanced Solid Tumors
Brief Summary Prospective, open-label, dose-ranging, uncontrolled phase I study with PM01183 in combination with irinotecan to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of PM01183 in combination with irinotecan in patients with selected advanced solid tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients with selected advanced solid tumors will be divided into two groups: the PM01183 Escalation Group and the Irinotecan Escalation Group. Each group will have a different dose escalation scheme.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: lurbinectedin (PM01183)
    lurbinectedin (PM01183) 4 mg vials
  • Drug: Irinotecan
    irinotecan 40 mg, 100 mg or 300 mg vials
Study Arms  ICMJE
  • Experimental: PM01183 Escalation Group

    PM01183 1.0 mg/m^2 D1 60 min (-5/+20 min) i.v. infusion q3wk

    Irinotecan 75 mg/m^2 D1-8 90 min (-5/+30 min) i.v. infusion q3wk

    Interventions:
    • Drug: lurbinectedin (PM01183)
    • Drug: Irinotecan
  • Experimental: Irinotecan Escalation Group

    PM01183 3.0 mg/m^2 D1 60 min (-5/+20 min) i.v. infusion q3wk

    Irinotecan 15 mg/m^2 D1-8 90 min (-5/+30 min) i.v. infusion q3wk

    Interventions:
    • Drug: lurbinectedin (PM01183)
    • Drug: Irinotecan
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 19, 2019)
150
Original Estimated Enrollment  ICMJE
 (submitted: November 18, 2015)
100
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Voluntarily signed and dated written informed consent prior to any specific-study procedure.
  2. Age ≥ 18 years.
  3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
  4. Life expectancy ≥ 3 months.
  5. No more than two prior lines of cytotoxic-containing chemotherapy regimens for advanced disease. There is no limit for prior targeted therapy, hormonal therapy and immunotherapy (such as nivolumab).
  6. Histologically or cytologically confirmed diagnosis of advanced disease of any of the following tumor types:

    1. Glioblastoma.
    2. Soft-tissue sarcoma [excluding gastrointestinal stromal tumors (GIST)].
    3. Endometrial carcinoma.
    4. Epithelial ovarian carcinoma (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas) regardless of platinum sensitivity.
    5. Mesothelioma.
    6. Gastroenteropancreatic neuroendocrine tumors (GEP-NET).
    7. Small cell lung cancer (SCLC).
    8. Pancreatic adenocarcinoma.
    9. Gastric carcinoma.
    10. Colorectal carcinoma (CRC).
  7. Expansion phase: Tumor-specific cohort(s) at the RD:

    1. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

      For patients with glioblastoma: Measurable disease according to RECIST v.1.1 and RANO criteria.

    2. Documented disease progression per RECIST v.1.1 during or immediately after last therapy according to any of the aforementioned criteria.

    For patients with glioblastoma: Documented disease progression per RECIST v.1.1 and RANO criteria.

  8. At least three weeks since the last anticancer therapy (excluding immunotherapy that must be at least two weeks, provided that is not combined with chemotherapy), including investigational drugs and radiotherapy, and at least six weeks since nitrosoureas and mitomycin C (systemic).

    For patients with glioblastoma: at least 12 weeks since the end of radiotherapy, except if:

    1. The patient has a new lesion outside of the radiotherapy field, or
    2. The patient has undergone brain surgery to remove the tumor before study entry, and progressive disease has been confirmed histologically.
  9. Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the study):

    1. Platelet count ≥ 100 × 10^9/L, hemoglobin ≥ 9.0 g/dL and absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L.
    2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × the upper limit of normal (ULN), even in the presence of liver metastases.
    3. Alkaline phosphatase (ALP) ≤ 2.5 × ULN (≤ 5 × ULN if disease-related/in the case of liver metastases).
    4. Total bilirubin ≤ 1.5 × ULN or direct bilirubin ≤ ULN.
    5. International Normalized Ratio (INR) < 1.5 (except if patient is on oral anticoagulation therapy).
    6. Calculated creatinine clearance (CrCL) ≥ 30 mL/minute (using Cockcroft-Gault formula).
    7. Creatine phosphokinase (CPK) ≤ 2.5 × ULN.
    8. Albumin ≥ 3.0 g/dL(*).
  10. Recovery to grade ≤ 1 or to baseline from any adverse event (AE) derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or peripheral neuropathy and/or fatigue grade ≤ 2).

(*)Albumin transfusion to increase the blood level in order to fulfill the inclusion criterion is strictly forbidden.

Exclusion Criteria:

  1. Concomitant diseases/conditions:

    1. History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within the previous year.
    2. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
    3. Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart).
    4. Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C. Known Gilbert disease.
    5. Active uncontrolled infection.
    6. Known human immunodeficiency virus (HIV) infection. Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV) infection or active hepatitis B.
    7. Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or sub-occlusion or paralysis.
    8. Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
    9. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
  2. Prior treatment with PM01183, trabectedin (Yondelis®) or topoisomerase I inhibitors (irinotecan, topotecan, etc.). Prior topoisomerase inhibitors (e.g., irinotecan) are only allowed in patients with colorectal carcinoma.
  3. Prior bone marrow or stem cell transplantation, or radiation therapy in more than 35% of bone marrow.
  4. Known brain metastases or leptomeningeal disease involvement. Glioblastoma lesions (primary or locally advanced) are eligible. In SCLC, patients with brain metastases or leptomeningeal disease involvement are eligible provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment (patients taking steroids in the process of already being tapered within two weeks prior to screening are allowed). Brain CT-scan or MRI results must be provided at baseline.
  5. Women who are pregnant or breast feeding and fertile patients (men and women) who are not using an effective method of contraception.(*)
  6. Limitation of the patient's ability to comply with the treatment or follow-up protocol.

(*)Women of childbearing potential (WOCBP) must agree to use an effective contraception method to avoid pregnancy during the course of the trial (and for at least three months after the last infusion). Fertile male patients must agree to refrain from fathering a child or donating sperm during the trial and for four months after the last infusion.

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: Pharma Mar Clinical Oncology clinicaltrials@pharmamar.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02611024
Other Study ID Numbers  ICMJE PM1183-A-014-15
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PharmaMar
Study Sponsor  ICMJE PharmaMar
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PharmaMar
Verification Date December 2019

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