Dose Escalation Study of LTX-315 in Patients With Transdermally Accessible Tumours
Conditions
Cancer - Melanoma - Breast Cancer - Head and Neck Cancer - Lymphoma
Conditions: official terms
Head and Neck Neoplasms
Conditions: Keywords
Transdermal accessible tumours
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: LTX-315
Type: Drug
Overall Status
Recruiting
Summary
The study will assess the safety, PK and efficacy of different dosing regimens of LTX-315; a lytic-peptide that induces long-term anti-cancer immune responses.
Detailed Description
In this phase I, open-label, multicentre, multi-dose study in patients with transdermally accessible tumours; the safety, PK and efficacy of different dosing regimens of LTX-315 will be asessed. The study will consist of two parts: Dose Escalation and Dose Expansion. In the Dose Escalation, each patient will have at least two lesions: a first index lesion for the Induction treatment and a second lesion for repeated Induction treatment and Maintenance treatment. The Dose Escalation consists of four periods: First induction treatment (up to 6 weeks of LTX-315) in the first index lesion; Second induction (up to 6 weeks of LTX-315) and Maintenance treatment (up to 20 weeks of LTX-315) in the second index lesion; Follow-up.

In the Dose Expansion each patient will have at least two lesions: a first index lesion for Induction and Maintenance treatment and a second lesion as a target (reference) lesion. The Dose Expansion will be done as determined by the Safety Review Committee and the Sponsor. The the optimal regimen will be based on the results of the Dose Escalation from the following information:

1. Safety parameters including blood samples and cardiovascular effects

2. Immunohistology and ultrasound confirmation of necrosis and tumour infiltrating lymphocytes

3. Systemic inflammatory response such as total lymphocyte count, C-reactive protein (CRP) or cytokines

4. Evidence of clinical responses

Cohorts may be utilised to:

1. Evaluate different doses of LTX-315

2. Explore potential modifications to the Induction and/or the Maintenance phases

3. Evaluate the potential to include appropriate combination therapies with LTX-315

4. Gain further information on clinical efficacy

Maintenance treatment may be extended for patients who have not progressed according to immune-related response criteria (irRC), as long as it is considered beneficial to the patient. Only adverse events and efficacy data will be collected on the extended Maintenance treatment.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Advanced disease for which conventional anti-tumour treatment is not appropriate.

- Have at least one transdermally injectable tumour (such as, but not limited to, melanoma, breast cancer, head/neck cancer or lymphoma) each of at least 10 mm and no greater than 100 mm in diameter.

- Have at least a single (irRC) measurable lesion in addition to the lesions chosen for transdermal injection (Expansion cohorts only).

- Be willing to undergo repeat tumour biopsy and/or tumour resection procedures.

- Have an ECOG Performance status (PS): 0 - 1.

- Meet the following laboratory requirements:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

2. Absolute lymphocyte count ≥ 0.8 x 109/L

3. Platelet count ≥ 75 x 109/L

4. Haemoglobin ≥ 9.0 g/dL

5. aPTT/PT within the institution's normal range

6. Total bilirubin level ≤ 1.5 x ULN

7. ASAT and ALAT ≤ 2.5 x ULN (≤5 x ULN if liver metastasis present)

8. Creatinine ≤ 1.5 x ULN

9. Albumin ≥ 30 g/L

Exclusion Criteria:

- Have received an investigational drug within 4 weeks prior to study drug administration, or are scheduled to receive one during the treatment or the post-treatment period.

- Have received cancer immunotherapy within 6 weeks prior to study drug administration or have not recovered from adverse events (to ≤ CTCAE grade 1) due to such agents.

- Have received any external radiotherapy to the index lesions or lesions identified as target lesions.

- Have index lesions scheduled to be resected within 6 weeks prior to study drug administration.

- Have received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to study drug administration, or have not recovered from adverse events (≤ CTCAE grade 1) due to agents administered more than 4 weeks earlier. Palliative radiotherapy to non-target lesions within 4 weeks of study drug administration is allowed provided that it is not in close proximity to a target lesion to be used of irRC assessment.

- Have received imiquimod within 12 weeks prior to study drug administration or have not recovered from adverse events (to ≤ CTCAE grade 1) due to this agent.

- Receiving full dose anticoagulation.

- Are currently taking any agent with a known effect on the immune system. Patients are allowed to be on a stable dose of corticosteroids (up to 10 mg daily prednisolone or equivalent) for at least 2 weeks prior to study drug administration (please see Appendix III for prohibited medications).

- Have any other serious illness or medical condition such as, but not limited to:

1. Uncontrolled infection or infection requiring antibiotics

2. Uncontrolled cardiac failure: Classification III or IV (New York Heart Association)

3. Uncontrolled systemic and gastro-intestinal inflammatory conditions

4. Bone marrow dysplasia

- Have a history of systemic auto-immune disease requiring anti-inflammatory or immunosuppressive therapy within the last 3 months. Patients with history of autoimmune thyroiditis are eligible provided the patient requires only thyroid hormone replacement therapy AND disease has been stable for ≥ 1 year.

- Have a known history of positive tests for HIV/AIDS, hepatitis B or C.

- Have a history of cerebrovascular or cardiac disorders and would be at particular risk of sequelae following a short hypotensive episode.

- Are breast feeding and/or have a positive pregnancy test during screening.

- Are expected to need any other anti-cancer therapy or immunotherapy to be initiated during the study period (induction and maintenance phases).
Locations
Cliniques Universitaires St-Luc, Service d'oncologie médicale
Bruxelles, Belgium
Status: Recruiting
Contact: Beatrice Vanderelst, RN - +32 2 7641299 - beatrice.vanderelst@uclouvain.be
Jules Bordet Institute
Bruxelles, Belgium
Status: Recruiting
Contact: Maureen Billiet, RN - +32 2 541 3303 - maureen.billiet@bordet.be
Institute Gustave Roussy
Paris, France
Status: Recruiting
Contact: Siham Farhane, RN - +33 142115 098
Haukeland University Hospital
Bergen, Norway
Status: Recruiting
Contact: Mari Holsen, RN - +47 55972890 - mari.helgesen.holsen@helse-bergen.no
Oslo University Hospital Radiumhospitalet
Oslo, Norway
Status: Recruiting
Contact: Paal Fr Brunsvig, MD PhD - +47 22934000 - pfb@ous-hf.no
Guy's Hospital
London, United Kingdom
Status: Recruiting
University College of London Hospital
London, United Kingdom
Status: Recruiting
Contact: Hazel Muteweri, RN - +44 20 3447 6032 - hazel.muteweri@uclh.nhs.uk
Start Date
November 2013
Sponsors
Lytix Biopharma AS
Source
Lytix Biopharma AS
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page