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

NCT01861496 | Completed Phase 1 DMC

• 2 other identifiers: LiPlaCis/P1/002SMR-3338
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

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.

Conditions

Phase 1: Advanced or Refractory Solid Tumours; Phase 2 Part: Metastatic Breast Cancer, Prostate Cancer and Skin Cancer

Keywords

Cisplatin; Liposomal formulation; DRP (Drug Response Prediction)

Outcome Measures

Primary Outcomes (1)

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

  Primary Objective: Assessment of adverse events and laboratory abnormalities

  one year

Secondary Outcomes (8)

• Maximum Observed Plasma Concentrations of platinum (Cmax)

  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

• Concentration of platinum (Pt-DNA)

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

• Area Under the Plasma - Time Concentration Curve (AUC)

  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

• Elimination half-life of platinum (T½)

  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

• Total body clearance of platinum (Cl)

  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

Study Arms (1)

LiPlaCis

EXPERIMENTAL

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.

Drug: LiPlaCis

Interventions

LiPlaCis DRUG

LiPlaCis IV every 3 weeks on day 1, day 8

Also known as: Liposomal formulation of Cisplatinum

LiPlaCis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Serum bilirubin \<= 1,5 ULN
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Allarity Therapeutics: lead

Study Sites (4)

The Phase One Unit, The Finsen Centre, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Herlev & Gentofte Hospital

Herlev, 2730, Denmark

Location

Nordsjællands Hospital Hillerød

Hillerød, 3400, Denmark

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Skin Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: May 23, 2013
• Study Start: April 1, 2013
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: February 24, 2022

Record last verified: 2022-02

Locations

DK (4)