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Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM060184 in Combination With Gemcitabine in Selected Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT02533674
Recruitment Status : Unknown
Verified July 2017 by PharmaMar.
Recruitment status was:  Recruiting
First Posted : August 27, 2015
Last Update Posted : July 5, 2017
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Brief Summary:

Prospective, open-label, dose-ranging, uncontrolled phase I study with escalating doses of PM060184 in combination with gemcitabine in selected patients with advanced solid tumors.

The study objectives are:

To determine the MTD and the RD of PM060184 in combination with gemcitabine in selected patients with advanced solid tumors.

To characterize the safety profile and feasibility of this combination in this study population.

To characterize the pharmacokinetics of this combination and to detect major drug-drug PK interactions.

To obtain preliminary information on the clinical antitumor activity of this combination.


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Gemcitabine plus PM060184 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM060184 in Combination With Gemcitabine in Selected Patients With Advanced Solid Tumors
Study Start Date : December 2014
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: gemcitabine plus PM060184 Drug: Gemcitabine plus PM060184



Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicities [ Time Frame: From the start of treatment to the end of cycle one which are 3 weeks ]
    Dose Limiting Toxicities will be listed and their incidence summarized by primary system organ class, worst grade based on CTCAE version 4.03 and type of Adverse Event


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: days 1 and 2 of cycles 1]. Patients included at the RD will be additionally evaluated on cycle 2 at the same time points ]

    Pharmacokinetics (PK) of PM060184, Gemcitabine and gemcitabine 2,2 -difluorodeoxyuridine (dFdU) will be evaluated during days 1 and 2 of cycle 1 at 10 time points: at baseline, just before end of infusion (EOT), then 10 min, 25 min, 40 min, 1.10 hs, 2.10 hs, 3.10 hs, 5.10 hs and 24 hs after the EOT .

    Pk analysis will be calculated using Non- Compartmental- Analysis (NCA) and population methods


  2. area under the curve (AUC) [ Time Frame: days 1 and 2 of cycles 1]. Patients included at the RD will be additionally evaluated on cycle 2 at the same time points ]
    Pharmacokinetics (PK) of PM060184, Gemcitabine and gemcitabine 2,2

  3. volume of distribution based on the terminal half-life (Vz) [ Time Frame: days 1 and 2 of cycles 1]. Patients included at the RD will be additionally evaluated on cycle 2 at the same time points ]
    Pharmacokinetics (PK) of PM060184, Gemcitabine and gemcitabine 2,2

  4. clearance (CL) [ Time Frame: days 1 and 2 of cycles 1]. Patients included at the RD will be additionally evaluated on cycle 2 at the same time points ]
    Pharmacokinetics (PK) of PM060184, Gemcitabine and gemcitabine 2,2

  5. volume of distribution at steady state (Vss) [ Time Frame: days 1 and 2 of cycles 1]. Patients included at the RD will be additionally evaluated on cycle 2 at the same time points ]
    Pharmacokinetics (PK) of PM060184, Gemcitabine and gemcitabine 2,2

  6. Antitumor activity of this combination. [ Time Frame: Baseline, then every 6 weeks, until disease progression or discontinuation an expected overage of 24 weeks ]
    This includes: response rate evaluated using RECIST V1.1 for most of the selected solid tumors and CHOI criteria and /or EORTC metabolic response criteria for gastrointestinal stromal tumor (GIST), also time related parameters [Progression Free Survival (PFS), Overall Survival and duration of response (DR) using the Kaplan-Meier (KM) method]]

  7. Number of subjects with Adverse Events as a Measure of Safety and Tolerability of PM060184 in combination with gemcitabine [ Time Frame: from the start of the treatment to the end of the treatment, an expected average of 24 weeks ]
    Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECG change monitoring as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03


Other Outcome Measures:
  1. Polymorphism analysis [ Time Frame: blood sample obtained pre-infusion of Cycle 1 day 1 ]
    Polymorphism analysis (pharmacogenetic) for presence or absence of germline mutations or polymorphism will be analyzed in leukocyte DNA extracted from a blood sample



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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) of ≤ 1 (see APPENDIX 1).
  4. Life expectancy ≥ 3 months.
  5. Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors that progressed to standard therapy or for whom no standard therapy exists:

    • Breast cancer non-candidate for hormone therapy alone.
    • Epithelial ovarian cancer (including primary peritoneal disease and/or fallopian tube carcinomas and/or endometrial adenocarcinomas).
    • Locally advanced or metastatic head and neck cancer.
    • Non-small cell lung cancer (NSCLC).
    • Germ cell tumors (GCTs).
    • Biliary tract adenocarcinoma.
    • Adenocarcinoma or carcinoma of unknown primary site (UKPS).
    • Cervix carcinoma.
    • Gastrointestinal stromal tumor (GIST).
    • Urothelial cancer.
  6. Expansion cohort at the RD:

    All patients must have:

    • Measurable disease according to RECIST v.1.1 (or Choi criteria and/or EORTC metabolic response criteria for solid tumors, in the case of GIST); or
    • Evaluable disease by serum markers in the case of ovarian cancer [Gynecologic Cancer Intergroup (GCIG) specific criteria]; and
    • Documented disease progression during or immediately after last therapy according to any of the aforementioned criteria.
  7. Wash-out periods: at least three weeks since the last anticancer therapy, including radiation therapy (RT) in more than 35% of the bone marrow; at least three weeks since the last biological/investigational therapy [excluding monoclonal antibodies (MAbs)]; at least four weeks since the last MAb-containing therapy; and at least six weeks since nitrosoureas and mitomycin C (systemic). In the case of hormonesensitive breast cancer progressing while on hormone therapy, the latter must be either stopped up to one week before or continued without changes during the trial.
  8. Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ 7 days before inclusion in the study):

    • Platelet count ≥ 100 x 109/l, hemoglobin ≥ 9.0 g/dl and ANC ≥ 1.0 x 109/l.
    • AST and ALT ≤ 3.0 x ULN, independently of the presence of liver metastases.
    • AP ≤ 2.5 x ULN (≤ 5 x ULN if disease-related).
    • Total bilirubin ≤ 1.5 x ULN.
    • International Normalized Ratio (INR) < 1.5 (except if patient is on oral anticoagulation therapy).
    • Calculated creatinine clearance (CrCl) ≥ 50 ml/minute (using Cockcroft and Gault's formula; see APPENDIX 2).
    • Albumin ≥ 2.5 g/dl.
  9. Recovery to grade ≤ 1 from any AE derived from previous treatment (excluding alopecia and/or cutaneous toxicity and/or asthenia).
  10. Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiplegated acquisition (MUGA) within normal range (according to institutional standards).
  11. Women of childbearing potential must have a negative serum or urine pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six weeks after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and/or double barrier.

Exclusion Criteria:

  1. Concomitant diseases/conditions:

    • History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
    • Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
    • Known chronic active hepatitis or cirrhosis
    • Active uncontrolled infection [i.e., antibiotic, antifungal or antiviral intervention indicated or surgical procedure (i.e., pleural or deep abscess drainage) conducted within 15 days prior to inclusion].
    • Known human immunodeficiency virus (HIV) infection.
    • Current or prior history of grade ≥ 2 peripheral sensory and/or motor neuropathy.
    • Prior treatment with oxaliplatin.
    • Limitation of the patient's ability to comply with the treatment or follow-up protocol.
    • 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. Symptomatic, progressive or corticosteroids-requiring documented brain metastases or leptomeningeal disease involvement.
  3. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding.
  4. Patients who have had RT in more than 35% of the bone marrow.
  5. Treatment with any investigational product within 30 days before the first infusion.
  6. Prior treatment with PM060184.
  7. Prior treatment with gemcitabine-containing therapy for advanced disease (adjuvant therapy is allowed, provided not more than six cycles were administered and relapse occurred more than six months after the last drug administration), and/or:

    • Patients who have previously discontinued gemcitabine-containing regimens due to gemcitabine-related toxicity.
  8. Known hypersensitivity to gemcitabine or any component of the formulation.

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 ClinicalTrials.gov identifier (NCT number): NCT02533674


Contacts
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Contact: Cinthya Coronado, MD clinicaltrials@pharmamar.com

Locations
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United States, New York
Recruiting
New York, New York, United States, 10461
Spain
Recruiting
Madrid, Spain
Sponsors and Collaborators
PharmaMar
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Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT02533674    
Other Study ID Numbers: PM60184-A-003-14
PM60184-A-003-14 ( Other Identifier: Pharma Mar USA, Inc. )
2014-002943-16 ( EudraCT Number )
First Posted: August 27, 2015    Key Record Dates
Last Update Posted: July 5, 2017
Last Verified: July 2017
Additional relevant MeSH terms:
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Neoplasms
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs