Clinical Trials /

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

NCT02611024

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Endometrial Adenocarcinoma
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Gastric Carcinoma
  • Gastrointestinal Neuroendocrine Tumors
  • Glioblastoma
  • Mesothelioma
  • Ovarian Carcinoma
  • Pancreatic Adenocarcinoma
  • Primary Peritoneal Carcinoma
  • Small Cell Lung Carcinoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pharmacokinetic Study of PM01183 in Combination With Irinotecan in Patients With Selected Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PM1183-A-014-15
  • NCT ID: NCT02611024

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
lurbinectedin ( PM01183)lurbinectedin (PM01183) + irinotecan
Irinotecanlurbinectedin (PM01183) + irinotecan

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
lurbinectedin (PM01183) + irinotecanExperimentalPM01183 1.0mg/m2 D1 1h i.v. infusion q3wk irinotecan 75mg/m2 D1-8 90min. i.v. infusion q3wk
  • lurbinectedin ( PM01183)
  • Irinotecan

Eligibility Criteria

        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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:36 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:AUC (area under the curve)
Time Frame:36 months
Safety Issue:
Description:
Measure:Clearance
Time Frame:36 months
Safety Issue:
Description:
Measure:Characterisation of Cmax (maximum concentration)
Time Frame:36 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PharmaMar

Trial Keywords

  • lurbinectedin
  • PM01183
  • tumors
  • cancer
  • Pharma Mar

Last Updated

September 21, 2016