OsteosarcomaPhase 1/2NCT04886765
A Study to Evaluate the Safety and Efficacy of ALMB-0168 in Patients With Osteosarcoma
A Phase 1/2 study testing ALMB-0168 in people with Osteosarcoma, run by AlaMab Therapeutics (Shanghai) Inc..
Trial summary
This is a phase I / II, multi-center, single-arm, open-label study to evaluate the safety and efficacy of ALMB-0168 in patients with osteosarcoma whose prior standard treatment have failed. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- ALMB-0168
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 238 participants
- Where
- No sites listed yet
- Study dates
- May 2021to May 2024
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histopathologically confirmed osteosarcoma;
- Patients will be enrolled according to different stages:
- Part I: Patients with osteosarcoma whose prior standard treatment have failed.;
- Part II: Patients with high-grade osteosarcoma whose prior standard treatment have failed.; Standard treatment failure is defined as the progression on or within 6 months after the first-line chemotherapy (including high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, etc.); For patients with disease progression more than 6 months after the chemotherapy, the risk-benefit assessment should be conducted by the investigators;
- 16 years of age or older, male or female;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2;
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- Either measurable or non-measurable disease per RECIST v1.1. Non-measurable disease should be assessable by conventional imaging techniques including isotope bone scans, CT or MRI scans. Patients in part II stage must have at least one measurable lesion confirmed by CT or MRI at baseline.
- Adequate major system function defined as:
- Bone marrow reserve: Absolute neutrophil count (ANC) ≥1.5 x109/L; Platelet count ≥ 75 x 109/L; Hemoglobin ≥ 90 g/L (not receiving blood transfusion within 14 days before the first administration);
- Hepatic function: Total bilirubin ≤1.5 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)) ≤ 3 x ULN (<5 x ULN for liver metastases);
- Renal function: Normal serum creatinine ≤1.5 mg/dL (133 μmol/L) OR calculated creatinine clearance ≥50 mL/min. (Cockcroft - Gault formula);
- Coagulation: Adequate coagulation parameters defined as International Normalization Ratio (INR) ≤2.
- Female patients of childbearing potential must have negative results of serum pregnancy test within 7 days before the first dose. Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including 1 barrier method, during their participation in the study and for 3 months following the last dose. Male patients must also refrain from donating sperm during their participation in the study;
- Life expectancy ≥3 months;
- Ability to understand the entire process of this study, voluntarily participate and sign a written informed consent form.
Who cannot join
- Any recent anti-tumour therapy ≤ 28 days before the first dose or residual more than Grade 1 chemotherapy-related side effects per NCI CTCAE v5.0, with the exception of alopecia.
- Have participated in the other clinical trial and received the investigational drug treatment within 4 weeks before the first dose of study drug;
- Wide-field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy;
- Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement;
- Brain metastases, leptomeningeal metastases or, spinal cord compression or central nervous system (CNS) injuries/abnormalities;
- Pregnant women. Breastfeeding women should stop breastfeeding before signing the informed consent;
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- Any of the following cardiac diseases currently or within the last 6 months:
- Left ventricular ejection fraction (LVEF) <45% as determined by echocardiogram (ECHO);
- The corrected QT interval (Fridericia formula) interval (QTcF) > 470 msec for females and > 450 msec for men in electrocardiogram (ECG) at screening;
- Unstable angina pectoris;
- Heart failure (New York Heart Association (NYHA) >2 grade);
- Acute myocardial infarction;
- Uncontrolled arrhythmia;
- Acute coronary syndromes;
- Stent placement;
- Uncontrolled hypertension (systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg (Patients with blood pressure values higher than these levels must use drugs to control blood pressure below this level before the first dose of study drug));
- Have a serious active infection (systemic intravenous antibiotics within 14 days but oral antibiotics allowed) that is not well controlled, or have another serious underlying medical condition that would prevent the patients from receiving the protocol treatment;
- Known diagnosis of human immunodeficiency virus, active hepatitis B or C;
- Have received Chinese herbal medicine or Chinese patent drug with anti-tumor activity within 14 days before the first administration;
- Has other active tumors or a history of infiltrative tumor treatment within 3 years. Patients with a history of definitively locally treated stage I tumors who are considered unlikely to recur can be accepted. Patients with a history of prior treatment for carcinoma in situ (e.g., non-invasive) and history of non-melanoma skin cancer are acceptable.
- According to the researchers' judgment, patients with other factors that may lead to the termination of the study, such as other serious diseases (including severe mental disorders) requiring combined treatment, serious laboratory abnormalities, family or social factors, which may affect the safety or the collection of data and samples. Psychological, family, social or geographical conditions and other factors are not consistent with the experimental scheme.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase I/II, Multi-center, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of ALMB-0168 in Patients With Osteosarcoma
This is a phase I / II, multi-center, single-arm, open-label study to evaluate the safety and efficacy of ALMB-0168 in patients with osteosarcoma whose prior standard treatment have failed.
Read the detailed description
This is a phase I / II, multi-centre, single-arm, open-label study with two parts, a dose-escalation phase (Part I) and a dose-expansion phase (part II). In part I, patients with osteosarcoma whose prior standard treatment have failed will be assigned to receive sequentially higher doses of ALMB-0168 intravenously. The dose-escalation initially will follow an accelerated titration design for the first two dosing groups, then follow a classic 3+3 design. The maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of ALMB-0168 will be determined in part I. In Part II, 1-3 expansion cohorts will begin to further assess the safety profile and explore efficacy, and each cohort will enroll up to 60 patients with high-grade osteosarcoma in each cohort. All patients will receive multiple administration of ALMB-0168 until either the disease progresses or intolerable toxicity occurs.
- Conditions
- Osteosarcoma
- Being tested
- ALMB-0168
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALMB-0168Drug
ALMB-0168 will be administered intravenously until either the disease progresses or intolerable toxicity occurs.
| Study group | Role | What they receive |
|---|---|---|
| ALMB-0168 | Experimental | Dose Escalation Cohort ：The accelerated titration and traditional "3+3" design will be used in the dose-escalation phase. Seven dose cohorts will be evaluated. ALMB-0168 will be administered intravenously once every 3 weeks until either the disease progresses or intolerable toxicity occurs.
Dose Expansion Cohort: Based on the results of Part I, 1-3 dose expansion cohorts will be started to further evaluate the safety and efficacy of ALMB-0168. Receives: Drug: ALMB-0168 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0). Incidence of adverse events will be assessed in both PART I and PART II.
Measured: From enrollment to 28 days after the last dose in each part study.
Dose-Limited Toxicities (DLT)
DLTs were assessed according to NCI-CTCAE v.5.0 during the first cycle
Measured: Up to 21 days in Cycle 1
6-Month Progression-free Survival Rate (6m-PFSR)
6m-PFSR is defined as the percentage of patients who will be alive and without PD at 6 months from the randomization date. 6m-PFSR will be assessed only in PART II.
Measured: From enrollment to 6 month after the first dose of the last patient in PART II
Secondary outcomes (20)
Maximum concentration (Cmax) of ALMB-0168
Measure the maximum (peak) plasma concentration
Measured: From enrollment to 4 weeks after the last dose of the last patient
Time to maximum concentration (Tmax) of ALMB-0168
Measure the time to reach maximum (peak) plasma concentration
Measured: From enrollment to 4 weeks after the last dose of the last patient
Minimum concentration(Cmin) of ALMB-0168
Measure the minimum (trough) plasma concentration
Measured: From enrollment to 4 weeks after the last dose of the last patient
The area under the curve (AUC) of ALMB-0168
Measure the area under the curve
Measured: From enrollment to 4 weeks after the last dose of the last patient
Half-life (t1/2) of ALMB-0168
calculate the half-life of ALMB-0168
Measured: From enrollment to 4 weeks after the last dose of the last patient
Clearance (CL) of ALMB-0168
Measure apparent total clearance(s) from plasma after administration
Measured: From enrollment to 4 weeks after the last dose of the last patient
Objective Response Rate (ORR)
ORR will be assessed by Blinded Independent Review Committee (IRC) per RECIST Version 1.1.
Measured: 2 year
Disease control rate (DCR)
DCR will be determined by Response evaluation criteria in solid tumours v1.1
Measured: 2 year
Duration of response (DOR)
DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) until progressive disease (PD) or death.
Measured: 2 year
Progression-free survival (PFS)
PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first.
Measured: up to 3 years
Time to Response (TTR)
TTR was defined as the time to a confirmed CR (disappearance of all target lesions) or PR (At least a 30 percent decrease in the sum of diameters of target lesions) per RECIST 1.1.
Measured: 2 year
Overall survival (OS)
OS was defined as the time from randomization to death due to any cause.
Measured: up to 3 years
Rate of Skeletal Related Events (SRE)
Including pathological fractures, spinal cord compression, hypercalcemia caused by malignant tumors, radiotherapy or surgery for bone lesions for symptom relief
Measured: through study completion, an average of 3 year
Change from baseline in alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)
pre- and post-treatment ALP and LDH changes in blood samples
Measured: through study completion, an average of 3 year
Change from baseline in Bone Mineral Density (BMD)
Dual-energy X-ray absorptiometry (DXA) to determine the bone mineral density of the subjects' lumbar spine, hip bone and femoral neck.
Measured: through study completion, an average of 3 year
Dose of morphine compared with baseline
pre- and post-treatment dose changes of morphine
Measured: through study completion, an average of 3 year
Frequency of morphine compared with baseline
pre- and post-treatment frequency changes of morphine
Measured: through study completion, an average of 3 year
Change from baseline of numeric pain scale (NRS) scores
pre- and post-treatment changes of NRS scores (min~max: 0~10; higher scores means a worse outcome)
Measured: through study completion, an average of 3 year
Change from baseline of quality of life scale (EQ-5D) scores
pre- and post-treatment changes of EQ-5D scores (min~max: 0~100; higher scores means a better outcome)
Measured: through study completion, an average of 3 year
The incidence of anti-drug antibody (ADA)
The percentage of patients with ADA
Measured: From enrollment to 4 weeks after the last dose of the last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2021
- Study startMay 2021 (estimated)
- Primary completionNov 2023 (estimated)
- Study completionMay 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Sequential
- Masking
- None (open label)
- Enrolment
- 238 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AlaMab Therapeutics (Shanghai) Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Jingnan Shen, Doctor, Principal investigator, the first affiliated Hospital, Sun Yat-sen Unibersity
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04886765
- Sponsor's protocol ID
- ALMB-0168-CN-101
- Status last verified
- May 2021
- First submitted
- 5 May 2021
- Last updated
- 14 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Multi-center, Single-Arm, Open-Label Study to Evaluate the Safety and Efficacy of ALMB-0168 in Patients With Osteosarcoma
- ClinicalTrials.gov ID
- NCT04886765
- Acronym / sponsor ID
- ALMB-0168-CN-101
- Conditions
- Osteosarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 238 participants (estimated)
- Lead sponsor
- AlaMab Therapeutics (Shanghai) Inc.Industry (pharma, biotech, devices)
- Collaborators
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Study start
- May 2021 (estimated)
- Primary completion
- Nov 2023 (estimated)
- Study completion
- May 2024 (estimated)
- First posted
- 14 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I / II, multi-center, single-arm, open-label study to evaluate the safety and efficacy of ALMB-0168 in patients with osteosarcoma whose prior standard treatment have failed.
Detailed description
This is a phase I / II, multi-centre, single-arm, open-label study with two parts, a dose-escalation phase (Part I) and a dose-expansion phase (part II). In part I, patients with osteosarcoma whose prior standard treatment have failed will be assigned to receive sequentially higher doses of ALMB-0168 intravenously. The dose-escalation initially will follow an accelerated titration design for the first two dosing groups, then follow a classic 3+3 design. The maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of ALMB-0168 will be determined in part I. In Part II, 1-3 expansion cohorts will begin to further assess the safety profile and explore efficacy, and each cohort will enroll up to 60 patients with high-grade osteosarcoma in each cohort. All patients will receive multiple administration of ALMB-0168 until either the disease progresses or intolerable toxicity occurs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ALMB-0168 | Experimental | Drug: ALMB-0168Dose Escalation Cohort ：The accelerated titration and traditional "3+3" design will be used in the dose-escalation phase. Seven dose cohorts will be evaluated. ALMB-0168 will be administered intravenously once every 3 weeks until either the disease progresses or intolerable toxicity occurs. Dose Expansion Cohort: Based on the results of Part I, 1-3 dose expansion cohorts will be started to further evaluate the safety and efficacy of ALMB-0168. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Histopathologically confirmed osteosarcoma;
- Patients will be enrolled according to different stages:
- 16 years of age or older, male or female;
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2;
- Either measurable or non-measurable disease per RECIST v1.1. Non-measurable disease should be assessable by conventional imaging techniques including isotope bone scans, CT or MRI scans. Patients in part II stage must have at least one measurable lesion confirmed by CT or MRI at baseline.
Key exclusion criteria (21 listed)
- Any recent anti-tumour therapy ≤ 28 days before the first dose or residual more than Grade 1 chemotherapy-related side effects per NCI CTCAE v5.0, with the exception of alopecia.
- Have participated in the other clinical trial and received the investigational drug treatment within 4 weeks before the first dose of study drug;
- Wide-field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy;
- Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement;
- Brain metastases, leptomeningeal metastases or, spinal cord compression or central nervous system (CNS) injuries/abnormalities;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALMB-0168ALMB-0168 will be administered intravenously until either the disease progresses or intolerable toxicity occurs. | Drug | ALMB-0168 |
Primary outcome
Incidence of adverse events
Time frame: From enrollment to 28 days after the last dose in each part study.
Defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0). Incidence of adverse events will be assessed in both PART I and PART II.
Dose-Limited Toxicities (DLT)
Time frame: Up to 21 days in Cycle 1
DLTs were assessed according to NCI-CTCAE v.5.0 during the first cycle
6-Month Progression-free Survival Rate (6m-PFSR)
Time frame: From enrollment to 6 month after the first dose of the last patient in PART II
6m-PFSR is defined as the percentage of patients who will be alive and without PD at 6 months from the randomization date. 6m-PFSR will be assessed only in PART II.
20 secondary outcomes
Maximum concentration (Cmax) of ALMB-0168
Time frame: From enrollment to 4 weeks after the last dose of the last patient
Time to maximum concentration (Tmax) of ALMB-0168
Time frame: From enrollment to 4 weeks after the last dose of the last patient
Minimum concentration(Cmin) of ALMB-0168
Time frame: From enrollment to 4 weeks after the last dose of the last patient
The area under the curve (AUC) of ALMB-0168
Time frame: From enrollment to 4 weeks after the last dose of the last patient
Half-life (t1/2) of ALMB-0168
Time frame: From enrollment to 4 weeks after the last dose of the last patient
Clearance (CL) of ALMB-0168
Time frame: From enrollment to 4 weeks after the last dose of the last patient
Objective Response Rate (ORR)
Time frame: 2 year
Disease control rate (DCR)
Time frame: 2 year
Duration of response (DOR)
Time frame: 2 year
Progression-free survival (PFS)
Time frame: up to 3 years
Time to Response (TTR)
Time frame: 2 year
Overall survival (OS)
Time frame: up to 3 years
Rate of Skeletal Related Events (SRE)
Time frame: through study completion, an average of 3 year
Change from baseline in alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)
Time frame: through study completion, an average of 3 year
Change from baseline in Bone Mineral Density (BMD)
Time frame: through study completion, an average of 3 year
Dose of morphine compared with baseline
Time frame: through study completion, an average of 3 year
Frequency of morphine compared with baseline
Time frame: through study completion, an average of 3 year
Change from baseline of numeric pain scale (NRS) scores
Time frame: through study completion, an average of 3 year
Change from baseline of quality of life scale (EQ-5D) scores
Time frame: through study completion, an average of 3 year
The incidence of anti-drug antibody (ADA)
Time frame: From enrollment to 4 weeks after the last dose of the last patient
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jingnan Shen, Doctor principal investigator
the first affiliated Hospital, Sun Yat-sen Unibersity
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ALMB-0168 in people with Osteosarcoma, run by AlaMab Therapeutics (Shanghai) Inc..
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 15 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 14 May 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaojing Lee, Master (+86-028-63925025, lixiaojing@mail.ecspc.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: From enrollment to 28 days after the last dose in each part study.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 May 2021.