A Phase 1/2a Study of LON002 in Subjects With Advanced Solid Tumours (LON002-002)

A Phase 1/2a Study of LON002 (Sublingual Artemether Spray) in Subjects With Advanced Solid Tumours.

This clinical trial will assess whether a medicine called artemether, currently used at a lower dose to treat malaria, could also be useful in treating cancer. For this trial, the medicine is given in a new way, as a spray under the tongue. This delivery has several advantages, including better absorption into the body and it may be easier for people to take. It will be prescribed to consenting patients with advanced solid tumours, every day for 4 months, either once or twice a day. (For this study 'advanced tumour' will mean there are no other effective standard therapy options available to the patient).

The dose will be decided in Phase 1 of the study by initially testing 3 different doses of the medicine in up to 21 different cancer patients, to make sure it is not too toxic or causes any side effects.

After this, the highest safe dose identified in the first phase will be tested in up to 66 cancer patients in Phase 2 of the study, to see if the medicine is able to reduce the size of their tumour or slow down its growth.

Study Overview

• Status: Unknown
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: Artemether

• Study Type: Interventional
• Enrollment (Anticipated): 87
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: London Pharma Ltd; Phone Number: 01865 784485; Email: davidlaskow-pooley@londonpharma.com

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's and St Thomas NHS Foundation Trust
    • Principal Investigator: Debashis Sarker, MD
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Not yet recruiting
      • The Royal Surrey County Hospital
      • Principal Investigator: Mazhar Ajaz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects of 18 years or older at the Screening Visit.
2. Histologic and/or cytologically confirmed diagnosis of solid tumour with clinical and imaging evidence that the tumour is advanced and for whom there is no effective standard therapy available.
3. At least one evaluable tumour that is at least 10 mm by computerised tomography (CT) scan or magnetic resonance imaging (MRI) at the pre-treatment stage
4. At least one prior systemic anti-cancer treatment and disease that is refractory or progressive following treatment.
5. Eastern Co operative Oncology Group (ECOG) performance ≤ 2.
6. An adequate renal, liver and bone marrow function.
7. Women of child bearing potential (WOCBP) must have a negative pregnancy test before the start of treatment.
8. Sexually active women of childbearing potential must be using an acceptable form of contraception, as detailed in the protocol.
9. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partner must meet the criteria defined in the protocol (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). Those with partners using hormonal contraceptives must also be using an additional approved method of barrier contraception.
10. Expected life expectancy > 4 months.

Exclusion Criteria:

1. Unwillingness or inability to provide informed consent.
2. Any evidence of severe or uncontrolled systemic diseases, infection or laboratory finding that in the view of the Investigator makes it undesirable for the patient to participate in the trial.
3. Allergic to artemether or other artemisinin derivatives or any of the components of the sublingual formulation.
4. Pregnancy or lactation.
5. Subject had major surgery or significant traumatic injury within 4 weeks of start of study drug; subject has not recovered from the side effects of any major surgery (defined as requiring general anaesthesia) or subject might require major surgery during the course of the study.
6. Subject has had anti-cancer treatment within 4 weeks of start of study drug, excluding small field palliative irradiation which may be performed up to 2 weeks prior to start of study drug.
7. Subject has had prior treatment with any investigational drug within the preceding 4 weeks before study start.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LON002; (Artemether sublingual spray)	Drug: Artemether; Artemether sublingual spray at 20mg per spray. Dose escalation study design as per protocol; in Phase 1, three dose levels will be given. The Phase 2 dose will be determined from the results of Phase 1. All patients will receive 4 cycles of dosing, 28 days per cycle.; Other Names: LON002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the Recommended Phase 2 Dose (RP2D) to be used in Phase 2a of the study		28 days
Number (%) of patients with clinical benefit in Phase 2a	Complete or partial response at any time based on imaging; Stable disease at 16 weeks (4 cycles); and/or; Reduction of validated biomarkers	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with Dose limiting toxicities	16 weeks
Time to progression (TTP), progression free survival (PFS) and overall survival (OS).	16 weeks

Collaborators and Investigators

• Sponsor: LondonPharma Ltd.
• Investigators: Principal Investigator: Debashis Sarker, MD, Guy's and St Thomas' NHS Foundation Trust; Principal Investigator: Mazhar Ajaz, MD, Royal Surrey County Hospital NHS Trust; Study Director: Daryl Bendel, MD, Xidea Solutions Ltd.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: October 8, 2014
• First Submitted That Met QC Criteria: October 14, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Estimate): September 7, 2015
• Last Update Submitted That Met QC Criteria: September 4, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Cancer; Chemotherapy; Artemether; Sublingual; Solid Tumour; Malignant Neoplasm; Neoplastic disease; Anti-cancer drug; LON002
• Additional Relevant MeSH Terms: Neoplasms; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Artemether
• Other Study ID Numbers: LON002-002