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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. Identifier: NCT02611024
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : October 11, 2018
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: lurbinectedin (PM01183) Drug: Irinotecan Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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
Official Title: Phase I, Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Pretreated Patients With Selected Advanced Solid Tumors
Actual Study Start Date : May 6, 2016
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: PM01183 Escalation Group

PM01183 1.0 mg/m2 D1 60 min i.v. infusion q3wk

Irinotecan 75 mg/m2 D1-8 90 min. i.v. infusion q3wk

Drug: lurbinectedin (PM01183)
lurbinectedin (PM01183) 4mg vials

Drug: Irinotecan
irinotecan 40 mg, 100 mg or 300 mg vials

Experimental: Irinotecan Escalation Group

PM01183 3.0 mg/m2 D1 60 min i.v. infusion q3wk

Irinotecan 15 mg/m2 D1-8 90 min. i.v. infusion q3wk

Drug: lurbinectedin (PM01183)
lurbinectedin (PM01183) 4mg vials

Drug: Irinotecan
irinotecan 40 mg, 100 mg or 300 mg vials

Primary Outcome Measures :
  1. 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.

  2. 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.

Secondary Outcome Measures :
  1. AUC (area under the curve) [ Time Frame: 48 months ]
  2. Clearance [ Time Frame: 48 months ]
  3. Characterisation of Cmax (maximum concentration) [ Time Frame: 48 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Voluntarily signed and dated written informed consent prior to any specific-study procedure.
  • Age between 18 and 70 years (both inclusive).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
  • Life expectancy ≥ 3 months.
  • 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).
  • 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 (GEPNET).
    7. Small cell lung cancer (SCLC).
    8. Pancreatic adenocarcinoma.
    9. Gastric carcinoma.
    10. Colorectal carcinoma (CRC).
  • Expansion phase: Tumor-specific cohort(s) at the RD:

    1. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
    2. Documented disease progression per RECIST v.1.1 during or immediately after last therapy according to any of the aforementioned criteria.
  • At least three weeks since the last anticancer therapy, including investigational drugs and radiotherapy, and at least six weeks since nitrosoureas and mitomycin C(systemic).
  • Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the study):

    1. Platelet count ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL and absolute neutrophil count (ANC) ≥ 2.0 × 109 /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.
  • 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).

Exclusion Criteria:

  • 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. Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C. Known Gilbert disease.
    4. Active uncontrolled infection.
    5. Known human immunodeficiency virus (HIV) or known hepatitis C virus (HCV) infection or active hepatitis B.
    6. Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 × ULN in two different determinations performed one week apart).
    7. Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion 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. Limitation of the patient's ability to comply with the treatment or follow-up protocol.
    10. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
  • Prior treatment with PM01183, trabectedin (Yondelis®) or topoisomerase I inhibitors (irinotecan, topotecan, etc.).
  • Prior bone marrow or stem cell transplantation, or radiation therapy in more than 35% of bone marrow.
  • Known brain metastases or leptomeningeal disease involvement. Glioblastoma lesions (primary or locally advanced) are eligible.
  • Women who are pregnant or breast feeding and fertile patients (men and women) who are not using an effective method of contraception. All patients (men and women) must agree to use an effective method of contraception (if applicable) up to three months after treatment discontinuation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02611024

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Contact: Pharma Mar Clinical Oncology

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United States, Massachusetts
Massachusetts General Hospital - Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Gregory Cote, MD, PhD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Principal Investigator: Luis Paz-Ares, Dr.         
Hospital Virgen Del Rocio Recruiting
Sevilla, Spain, 41013
Principal Investigator: María José Flor Oncala, Dra.         
Sponsors and Collaborators

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Responsible Party: PharmaMar Identifier: NCT02611024     History of Changes
Other Study ID Numbers: PM1183-A-014-15
First Posted: November 20, 2015    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018

Keywords provided by PharmaMar:
Pharma Mar

Additional relevant MeSH terms:
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Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents