A Phase 1 Trial of ALMB-0168 in Patients with Malignant Bone Disease
Phase 1, Multicenter, First-in-Human Dose Escalation Study of ALMB-0168 Administered IV as a Single Agent to Patients with Malignant Bone Disease
Avance Clinical Pty Ltd
35 participants
Oct 23, 2020
Interventional
Conditions
Summary
The purpose of this study is to test the safety of a new medication (called ALMB-0168) in people with malignant bone cancer lesions either from bone cancer or from migration of other cancers. Who is it for? You may be eligible for this study if you are aged 16 or older, and have confirmed bone cancer (osteosarcoma) or cancer cells in the bone originated from other cancers which has been deemed untreatable. Study details All participants in this study will receive the active medication ALMB-0168. The dose will depend on when the participant enrolls in the study. The medication is administered through a needle in the arm, and will continue for up to 6 months. As part of this study, all participants will have additional blood tests, imaging scans and answer questions regarding to your health. It is hoped this research will demonstrate the safety of ALMB-0168 and find the ideal dose for larger-scale studies.
Eligibility
Inclusion Criteria18
- Pathological confirmation (histological or cytological) of cancer: Osteosarcoma or any other solid tumour cancer.
- Presence of either:
- a. Locally advanced or relapsed osteosarcoma considered to be incurable by the investigator and for which there is no available therapies;
- b. Advanced solid tumour with bone metastatic cancer considered to be incurable by the investigator and for which available anti-cancer therapy has been exhausted, refused or not tolerated. Breast Cancer (BC) or Prostate Cancer (PC) subjects with bone metastases and who have been under hormonal therapy as Standard of Care (SOC) for underling cancer for at least 3 months and with stable dose and clinical status maybe allowed to enrol. The same applies to SOC bisphosphonates and denosumab, which are also allowable if the subject has been receiving this treatment for a period of at least 3 months at a stable dose prior to screening.
- Male or female 16 years of age or older for subjects with osteosarcoma, or 18 years or older for subjects with all other tumour types.
- ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0, 1 or 2
- Either measurable or non-measurable disease. Non-measurable disease should be assessable by conventional imaging techniques including isotope bone scans, CT or MRI
- scans.
- Adequate major system function defined as:
- a. Bone marrow reserve: Absolute neutrophil count (ANC) greater than or equal to 1.5 x109/L; Platelet count greater than or equal to 100 x 109/L; Haemoglobin greater than or equal to 90 g/L
- b. Hepatic function: Total bilirubin lesser than or equal to1.5 x upper limit of normal (ULN) Transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and/or alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) lesser than or equal to 3 x ULN (lesser than 5 x ULN if liver metastases);
- c. Renal function: Normal serum creatinine lesser than or equal to 1.5 mg/dL (133 µmol/L) OR calculated creatinine clearance greater than or equal to 50 mL/min.
- d. Coagulation: Adequate coagulation parameters defined as International Normalization Ratio (INR) lesser than or equal to 2.
- Male participants with female partners of childbearing potential and women participants of
- childbearing potential are required to use two forms of acceptable contraception, including 1 barrier method, during their participation in the study and for 30 days following last dose. Male subjects must also refrain from donating sperm during their participation in the study.
- Life expectancy greater than or equal to 3 months.
- Willingness and ability to comply with study and follow-up procedures.
- Ability to understand the nature of this study and give written informed consent.
Exclusion Criteria19
- Most recent chemotherapy lesser than or equal to14 days or have residual NCI CTCAE greater than or equal to Grade 1 chemotherapy-related side effects, with the exception of alopecia.
- Use of any experimental study drug lesser than or equal to 21 days or 5 half-lives (whichever is shorter) prior to the first dose of ALMB-0168. For study drugs for which 5 half-lives is lesser than or equal to 21 days such as tyrosine kinase inhibitor (TKI), a minimum of 10 days between termination of the study drug and administration of ALMB-0168 is required. For certain immune-oncology drugs that have longer half-lives, a washout period of 4 weeks may be required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered lesser than or equal to 28 days or limited field radiation for palliation lesser than or equal to 7 days prior to starting study drug or has not recovered from side effects of such therapy.
- Major surgical procedures lesser than or equal to 28 days of beginning study drug, or minor surgical procedures lesser than or equal to 7 days. No waiting required following port-a-cath placement.
- Brain metastases or CNS injuries / abnormalities by history or as determined by brain MRI.
- Leptomeningeal metastases or spinal cord compression due to disease.
- Pregnant or lactating.
- Any of the following cardiac diseases currently or within the last 6 months:
- Left ventricular ejection fraction (LVEF) lesser than 45% as determined by multiple gated
- acquisition (MUGA) scan or echocardiogram (ECHO);
- QTc interval greater than 470 msec for females and greater than 450 msec for men on screening electrocardiogram (ECG);
- Unstable angina pectoris;
- New York Heart Association Class III or IV heart failure, acute myocardial infarction, angina pectoris, uncontrolled arrhythmia, acute coronary syndromes, stent placement, uncontrolled hypertension
- Serious active infection at the time of treatment (no systemic intravenous antibiotics within 14 days; oral antibiotics is allowed), or another serious underlying medical condition that would impair the ability of the subject to receive protocol treatment.
- Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin
- that has undergone potentially curative therapy or in situ cervical cancer
- Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
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Interventions
Each participant will receive a weight-based single dose ALMB-0168 as IV injection at one of the 7 dose levels (1mg/kg to 3mg/kg, 6mg/kg, 12mg/kg, 20mg/kg, 25mg/kg and 30mg/kg) on Day 1 of every 21-day cycle for up to 6 months or maximally 8 cycles. As this is an open-label study, no randomisation will be performed. Assignment of a patient to a particular dose level will be coordinated by the sponsor upon patient registration. Treatment will be discontinued when disease progression or a change of therapy is necessary. Per Investigator's discretion, ALMB-0168 treatment may be given for longer term to subjects who can continue benefit from it.
Locations(3)
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ACTRN12620000440921