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Phase 1: Advanced or Refractory Solid TumoursPhase 1/2LiPlaCisNCT01861496

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

A Phase 1/2 study testing LiPlaCis in people with Phase 1: Advanced or Refractory Solid Tumours and Phase 2 Part: Metastatic Breast Cancer, Prostate Cancer and Skin Cancer, run by Allarity Therapeutics at 4 sites in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LiPlaCis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
4 sitesDenmark
Study dates
Apr 2013to Oct 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • >= 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

4 sites in 1 country.

Denmark4 sites

  • The Phase One Unit, The Finsen Centre, Rigshospitalet

    Copenhagen, DK-2100

  • Herlev & Gentofte Hospital

    Herlev, 2730

  • Nordsjællands Hospital Hillerød

    Hillerød, 3400

  • Vejle Sygehus

    Vejle, 7100

Other trials in Denmark

About this study

Official title: Phase I/II Study to Evaluate the Safety and Tolerability of LiPlaCis (Liposomal Cisplatin Formulation) in Patients With Advanced or Refractory Tumours

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.

Read more

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.

Being tested
LiPlaCis
Keywords
Cisplatin, Liposomal formulation, DRP (Drug Response Prediction)
Medical subject headings
Prostatic Neoplasms, Skin Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LiPlaCisDrug

    Also called Liposomal formulation of Cisplatinum

    LiPlaCis IV every 3 weeks on day 1, day 8

Study groups in NCT01861496
Study groupRoleWhat they receive
LiPlaCisExperimentalDose 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.
Receives: Drug: LiPlaCis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability

    Primary Objective:

    Assessment of adverse events and laboratory abnormalities

    Measured: one year

Secondary outcomes (8)

  1. Maximum Observed Plasma Concentrations of platinum (Cmax)

    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.

    Measured: 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

  2. Concentration of platinum (Pt-DNA)

    Tumor and normal tissue biopsies are obtained concentrations of platinum are determined using a validated method.

    Measured: Prior to the initial dose on day 1and 24 hours after

  3. Area Under the Plasma - Time Concentration Curve (AUC)

    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.

    Measured: 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

  4. Elimination half-life of platinum (T½)

    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.

    Measured: 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

  5. Total body clearance of platinum (Cl)

    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.

    Measured: 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

  6. Volume of distribution of platinum at steady state (Vss)

    Blood samples are obtained and plasma concentrations of total LiPlaCis-derived platinum are determined using a validated atomic absorption spectrometry method.

    Measured: 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

  7. Therapeutic efficacy of LiPlaCis (Efficacy Endpoint)

    Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.

    Measured: Tumor Assessed every 6 weeks until and at end of treatment, with an expected average of 3 treatment cycles (9 weeks)

  8. Progression Free Survival

    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.

    Measured: one year after end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2013 (estimated)
  2. Study startApr 2013
  3. Primary completionOct 2021
  4. Study completionOct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01861496
Sponsor's protocol ID
LiPlaCis/P1/002
Other IDs
SMR-3338
Acronym
LiPlaCis
Status last verified
Feb 2022
First submitted
1 May 2013
Last updated
24 Feb 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LiPlaCis in people with Phase 1: Advanced or Refractory Solid Tumours and Phase 2 Part: Metastatic Breast Cancer, Prostate Cancer and Skin Cancer, run by Allarity Therapeutics at 4 sites in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability (time frame: one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01861496.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2022.

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