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Phase I/II Study to Evaluate the Safety and Tolerability of LiPlaCis in Patients With Advanced or Refractory Tumours (LiPlaCis)

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: NCT01861496
Recruitment Status : Active, not recruiting
First Posted : May 23, 2013
Last Update Posted : July 28, 2021
Sponsor:
Information provided by (Responsible Party):
Allarity Therapeutics

Tracking Information
First Submitted Date  ICMJE May 1, 2013
First Posted Date  ICMJE May 23, 2013
Last Update Posted Date July 28, 2021
Study Start Date  ICMJE April 2013
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2013)
Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability [ Time Frame: one year ]
Primary Objective: Assessment of adverse events and laboratory abnormalities
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2017)
  • Maximum Observed Plasma Concentrations of platinum (Cmax) [ Time Frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Concentration of platinum (Pt-DNA) [ Time Frame: Prior to the initial dose on day 1and 24 hours after ]
    Tumor and normal tissue biopsies are obtained concentrations of platinum are determined using a validated method.
  • Area Under the Plasma - Time Concentration Curve (AUC) [ Time Frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Elimination half-life of platinum (T½) [ Time Frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Total body clearance of platinum (Cl) [ Time Frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Volume of distribution of platinum at steady state (Vss) [ Time Frame: Prior to the initial dose on day 1, day 8 and 15 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Therapeutic efficacy of LiPlaCis (Efficacy Endpoint) [ Time Frame: Tumor Assessed every 6 weeks until and at end of treatment, with an expected average of 3 treatment cycles (9 weeks) ]
    Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
  • Progression Free Survival [ Time Frame: one year after end of treatment ]
    PFS for patients at dose step 5 and up by Response and progression evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2013)
  • Maximum Observed Plasma Concentrations of platinum (Cmax) [ Time Frame: Prior to the initial dose on day 1 and 8 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Area Under the Plasma - Time Concentration Curve (AUC) [ Time Frame: Prior to the initial dose on day 1 and 8 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Elimination half-life of platinum (T½) [ Time Frame: Prior to the initial dose on day 1 and 8 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Total body clearance of platinum (Cl) [ Time Frame: Prior to the initial dose on day 1 and 8 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Volume of distribution of platinum at steady state (Vss) [ Time Frame: Prior to the initial dose on day 1 and 8 and 5 min before end of infusion, 5 min, 0,5, 1, 3, 7, 24, 48, 72 hours post dose ]
    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.
  • Therapeutic efficacy of LiPlaCis (Efficacy Endpoint) [ Time Frame: Tumor Assessed every 6 weeks until and at end of treatment, with an expected average of 3 treatment cycles (9 weeks) ]
    Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/II Study to Evaluate the Safety and Tolerability of LiPlaCis in Patients With Advanced or Refractory Tumours
Official Title  ICMJE Phase I/II Study to Evaluate the Safety and Tolerability of LiPlaCis (Liposomal Cisplatin Formulation) in Patients With Advanced or Refractory Tumours
Brief Summary

Liposomal formulations are frequently used today in the treatment of cancer. LiPlaCis is the first targeted liposomal formulation with a tumour triggered release mechanism to undergo clinical development in oncology and it is expected that LiPlaCis will improve the therapeutic index of cisplatin compared to conventional cisplatin.

Cisplatin is one of the most widely used drugs in the treatment of cancer due to its documented efficacy in a number of tumour types. Furthermore, it seems highly likely that cisplatin will remain an important drug in the future treatment of cancer. However, the drug is associated with a number of serious toxicities that complicates or necessitates discontinuation of therapy - e.g. need for pre-hydration, neurotoxicity, nausea and vomiting.

Thus, there is a well-established need for improving cisplatin therapy in cancer patients. One option here is improving the formulation of the drug, so that a more selective up-take of cisplatin administered takes place at the tumour sites.

Based on the results of the pre-clinical studies of LiPlaCis, it seems clear that LiPlaCis offers the potential to improve cisplatin therapy to the benefits of cancer patients.

In a prematurely stopped Phase I Dutch study a Recommended Dose (RD) for a Phase II study was never reached which was the aim of the finished Phase I dose escalating part of this study for advanced or refractory solid tumors.

In the Phase 2 part of this study, patients with advanced breast cancer with a biopsy examination showing a pattern compatible with sensitivity to LiPlaCis or patients with skin cancer will be included.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Phase 1: Advanced or Refractory Solid Tumours
  • Phase 2 Part: Metastatic Breast Cancer, Prostate Cancer and Skin Cancer
Intervention  ICMJE Drug: LiPlaCis
LiPlaCis IV every 3 weeks on day 1, day 8
Other Name: Liposomal formulation of Cisplatinum
Study Arms  ICMJE Experimental: LiPlaCis
Dose escalation of LiPlaCis - a liposomal formulation of cisplatin will be administered intravenously in cycles every 3 weeks on day 1, day 8. Upon the investigator's judgement the patient may continue treatment for more than 3 cycles when benefiting from the study drug.
Intervention: Drug: LiPlaCis
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: March 6, 2019)
50
Original Estimated Enrollment  ICMJE
 (submitted: May 21, 2013)
18
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological or cytological documented locally advanced or metastatic solid tumour relapsed on 2 or more different prior therapies. From step 5 and extension phase, population limited to Skin Cancer patients (non screened) or metastatic Breast Cancer patients or metastatic castration-resistant prostate cancer patients screened sensitive to LiPlaCis.
  • Age >= 18 years.
  • Life expectancy >= 3 months.
  • ECOG performance status of 0 - 1.
  • Recovered to Grade 1 or less from acute toxicities of prior treatment.
  • >= 6 months must have elapsed since patient received cisplatin.
  • >= 4 weeks must have elapsed since patient received any investigational medicinal product.
  • >= 4 weeks must have elapsed since patient received any radiotherapy(except for palliative radiotherapy on non-target lesions), or treatment with cytotoxic or biologic agents (>=6 weeks for mitomycin or nitrosoureas). No hormonal treatment is allowed except treatment with corticosteroids at physiological dose and hormonal treatment with LHRH agonists for prostate cancer.
  • >=2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF.
  • Adequate condition as evidenced by the following clinical laboratory values:

    • Absolute neutrophil count (ANC) >= 1,5 x 10E9/L
    • Haemoglobin is at least 4,6 mmol/L
    • Platelets >= 75 x 10E9/L
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2,5 x ULN, in case of known liver metastases ALT and AST <= 5 x ULN. Patients who does not conform to the transaminase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase levels are considered elevated due to other reasons than deteriorated liver capacity, may be considered for inclusion based on conferred agreement between PI and Sponsor
    • Serum bilirubin <= 1,5 ULN
    • Alkaline phosphatase <= 2,5 x ULN, in case of known liver metastases <= 5 x ULN. Patients who does not conform to the Alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the Alkaline phosphatase levels are considered elevated due to other reasons than deteriorated liver capacity, may be considered for inclusion based on conferred agreement between PI and Sponsor
    • Blood urea within normal limits, creatinine below upper normal limits and creatinine clearance within normal limits (>= 60 mL/min Cr-EDTA clearance).In the case of hydronephrosis, renography must be considered prior to treatment with LiPlaCis. For signs of drainage obstacle, well-functioning renal excretion/effect and normal diuresis must be ensured, e.g. via a double-J catheter.
  • Sexually active males and females of child-producing potential, must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards.
  • Patient must understand the investigational nature of this study and sign an independent ethical committee (IEC) approved written informed consent form prior to any study related activities.

Exclusion Criteria:

  • Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
  • Any active infection requiring parenteral or oral antibiotic treatment.
  • Known infection with human immunodeficiency virus (HIV) or hepatitis virus.
  • Pre-existing renal insufficiency. Please refer to inclusion criteria no. 10g.
  • Active heart disease including myocardial infarction or congestive heart failure within the previous 6 months, symptomatic coronary artery disease, or symptomatic arrhythmias currently requiring medication.
  • Known or suspected active central nervous system (CNS metastasis). (Patients stable 8 weeks after completion of treatment for CNS metastasis are eligible).
  • Autoimmune disease.
  • Impending or symptomatic spinal cord compression or carcinomatous meningitis.
  • Pre-existing neuropathy, i.e., Grade >1 neuromotor or neurosensory toxicity (as defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4,0), except for abnormalities due to cancer.
  • Known hypersensitivity to cisplatin or liposomes.
  • Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy(except for palliative radiotherapy on non-target lesions).
  • Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry).
  • Unwilling or unable to follow protocol requirements.
  • Previous progression on a platinum containing therapy.
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 Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01861496
Other Study ID Numbers  ICMJE LiPlaCis/P1/002
SMR-3338 ( Other Identifier: Smerud Medical Research, Denmark )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Allarity Therapeutics
Study Sponsor  ICMJE Allarity Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ulrik Lassen, Professor MD, Ph.D Rigshospitalet, Finsen Centre, Oncology Department, Phase 1 Unit
Principal Investigator: Dorte Nielsen, Professor MD, Ph.D Herlev&Gentofte Hospital, Oncology Department
PRS Account Allarity Therapeutics
Verification Date February 2021

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