Advanced Solid TumorPhase 1NCT03260179
Study to Evaluate the Safety, Preliminary Efficacy and Pharmacokinetics of 3810
A Phase 1 study testing AL3810 in people with Advanced Solid Tumor and Advanced/Metastatic Colorectal Cancer, run by Haihe Biopharma Co., Ltd. at 7 sites in China.
Trial summary
This project intends to make a study of personalized medicine evaluation system establishment for liver cancer, gastric cancer and nasopharynx cancer to provide strong support for the development of Precision Medicine and personalized medicine for the patients of high-incidence-rates cancer in China. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Solid Tumor, Advanced/Metastatic Colorectal Cancer
- What is being tested?
- AL3810
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 7 sitesChina
- Study dates
- 31 Aug 2017to 30 Jun 2019
- Phase
- Phase 1
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Main criteria for inclusion:
- Adult male or female Chinese subject aged 18 to 70 years, inclusive, at the time of signing the informed consent form, with weight at least 40 kg when screening.
- Life expectancy ≥ 12 weeks as judged by the Investigator.
- Histologically or cytologically confirmed, locally advanced or metastatic solid tumor and be limited to:
- Gastric carcinoma (including gastro-oesophageal junction adenocarcinoma).
- Hepatocellular carcinoma (Child-Pugh Class A).
- Undifferentiated nasopharyngeal carcinoma.
- Each subject should provide at least 5 slides for the formalin fixed and paraffin embedded tumor biopsy (undyed) at the baseline, fresh biopsy or most recent primary tumor sample or metastatic sample is required.
- Patients, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists.
- Toxicities from any prior therapy, surgery, or radiotherapy must have resolved to Grade ≤ 1 as per the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), excluding alopecia and peripheral neuropathy. For subjects having a prior platinum-based therapy, peripheral neuropathy are required to recover to ≤ CTCAE grade 2.
- Per RECIST v1.1 guidelines for solid tumors:
- Patients with gastric carcinoma should have at least one measurable lesion beyond stomach,
- Patients with Hepatocellular carcinoma and undifferentiated nasopharyngeal carcinoma should have at least one measurable lesion.
- Adequate bone marrow and organ function as defined by the following laboratory values: (prophylactic use of myeloid growth factors (eg, G-CSF, GM-CSF) is prohibited within 2 weeks before screening)
- Absolute neutrophil count (ANC) ≥ 1.5x 109/L.
- Platelet counts ≥ 100 x 109/L.
- Haemoglobin ≥ 90 g/L (without blood transfusion within the last 2 weeks from screening).
- Creatinine clearance > 50 mL/min (calculated according to Cockroft-Gault formula).
- Proteinuria < 1+. If proteinuria ≥ 1+, urine protein quantitation over 24 hours should be < 1.0 g/24hrs.
- INR ≤ 1.5 and APTT≤ 1.5 Upper Limit of Normal (ULN).
- AST, ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases or hepatocellular carcinomas are present).
- Total Bilirubin < 1.5 x ULN.
- For Hepatocellular carcinomas patients, albumin ≥ 28 g/dL.
- Patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1.
- Patient is able to swallow and retain oral medication.
- Female subjects, with childbearing potential, has a negative serum pregnancy test at screening (within 7 days of the first investigational product administration). The definition of women with child-bearing potential are defined as "All female subjects after puberty unless they are post-menopausal or not sexually active". Females are considered postmenopausal if they have age-related amenorrhea ≥ 12 consecutive months or if they have undergone hysterectomy or bilateral oophorectomy.
- Patients who have fully understood the study, and have signed the general Informed Consent Form (ICF) prior to any screening procedures being performed
Main criteria for non-inclusion
- Patient who has participated in another interventional trial within 28 days prior to starting study medicine. If a subject is joining a non-interventional trial, such as an epidemiological study, or in a survival follow-up period of an interventional trial, he or she may participate in this trial.
- Expected poor compliance during the study.
- Patient has symptomatic CNS metastases requiring clinical intervention. The stable patient may participate in this trial, who must have completed any prior local treatment for CNS metastases ≥ 14 days prior to the start of study treatment (including radiotherapy and/or low dose steroid therapy).
- Patient has a concurrent malignancy or malignancy within 2 years of study enrolment, with the exception of adequately treated and cured non-melanomatous skin cancer, carcinoma in situ of breast and cervix, and superficial bladder cancer.
- Patient who has received chemotherapy, targeted therapy or immunotherapy within 28 days or ≤ 5 half-lives prior to starting study medicine. Take the longer one. For HCC patient who has received any prior local therapy (hepatic arterial embolization, transcatheter arterial chemoembolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within 4 weeks of starting study medicine •.
- Previous treatment with Bevacizumab within 3 months of starting AL3810. In addition:
- Patients with nasopharyngeal carcinoma who received antiangiogenic agent are not allowed.
- Patients with nasopharyngeal carcinoma located within 5mm of large blood vessels.
- Patient who has received wide field radiotherapy within 28 days prior to starting study medicine
- Patient who has received a major surgery within 28 days prior to starting study medicine. The definition of a major surgery refers to grade 3 and 4 surgery specified in <Management of Clinical Practice of Medical Technologies> effective on May 1, 2009 in China,
- Patient has active cardiac disease or a history of cardiac dysfunction in screening including any of the following:
- History of documented Congestive heart failure ≥ class II (NYHA New York Heart Association functional classification) or requiring therapy,
- Ventricular and/or supraventricular arrhythmia requiring therapy;
- Severe conduction disturbance (including QTc interval prolongation > 450msec [corrected by Fredericia formula], history of severe arrhythmia, or history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome]),
- Angina pectoris requiring therapy,
- Left ventricular ejection fraction (LVEF) < 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA) ,
- Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg with optimized antihypertensive therapy or patients treated with ≥ 2 antihypertensive agents),
- Hypertension with systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg with or without antihypertensive therapy.
- Conduction abnormality requiring a pacemaker or implanted a pacemaker.
- History of clinically significant or uncontrolled cardiac disease within 6 months prior to starting AL3810, including angina, myocardial infarction, and stroke.
- Patients with thromboembolic events within 12 months prior to starting AL3810, or at a high risk of such events.
- Patient with hereditary risks of thromboembolic events.
- Patient is currently receiving treatment with warfarin or any other oral Anticoagulants
- Patients with active HBV or HCV infection or known positivity for human immunodeficiency virus (HIV) infection are not allowed. HBV, HCV and HIV will be tested in the screening. Serum HBsAg positive with HBV DNA <104 Copy/mL may participate study. Prophylactic anti-HBV medications application can be accepted. Serum HCV or HIV antibody positive is not allowed.
- Patients receiving medications known to prolong QTc interval and that may be associated with Torsades de Pointes.
- Serum potassium (K+) levels below LLN at screening period.
- Patients who received administration of strong inhibitors of CYP2C8 and/or CYP3A4 or strong inducers of CYP3A4 within 7 days or ≤ 5 half-lives (Take the longer one) prior to starting AL3810. And patient cannot stop taking the medication. .
- Significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhoea associated with intestinal malabsorption, the Crohn's disease, or significant abnormalities decided by investigator. In addition, patients with any grade of gastro-intestinal bleeding events within 3 months prior to starting AL3810 are not allowed.
- History of grade 3 haemorrhage/bleeding events within 6 months prior to starting AL3810, or history of grade 4 haemorrhage/bleeding events.
- Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, thyroid and adrenal gland.
- Serious/active bacterial, viral or fungal infection requiring systemic treatment.
- Concomitant uncontrolled severe systemic disease (e.g., uncontrolled diabetes mellitus, uncontrolled ascites, etc.).
- Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures.
- Known organ dysfunction which would either compromise the patient's safety or interfere with the evaluation of AL3810.
- Male patients and female patients of child bearing potential unable or unwilling to employ effective contraception (abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive for women and barrier method) during the study and for 6 months thereafter.
- Breastfeeding women.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
China7 sites
The 307th Hospital of Chinese People's Liberation Army
Beijing, Beijing Municipality
Xu Jian ming, MD
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong
Xu Rui hua, MD, 13922206676, xurh@sysucc.org.cn
Sun Yat-sen University
Guangzhou, Guangdong
Zhang li, MD, 13902282893, zhangli@sysucc.org.cn
Sun Yat-sen University Cancer Center
Hangzhou, Zhejiang
The 81st Hospital of People's Liberation Army
Nanjing, Jiangsu, 210002
Qin Shu kui, MD, 13905158713, qinsk@csco.org.cn
Jiangsu Cancer Hospital
Nanjing, Jiangsu
Feng Ji feng, MD, 13901581264, fjif@vip.sina.com
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200000
Cao Jun ning, MD, 13651680209, cao_junning@126.com
About this study
Official title: An Open-label Phase Ib, Study, to Determine Safety of Oral AL3810 in Patients With Locally Advanced or Metastatic Gastric, Hepatocellular or Nasopharyngeal Carcinoma
This project intends to make a study of personalized medicine evaluation system establishment for liver cancer, gastric cancer and nasopharynx cancer to provide strong support for the development of Precision Medicine and personalized medicine for the patients of high-incidence-rates cancer in China.
- Being tested
- AL3810
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AL3810Drug
Fasting,oral ,4w on or 3w on/1w off
AL3810Drug
Fasting,oral ,4w on or 3w on/1w off
AL3810Drug
Fasting,oral ,4w on or 3w on/1w off
| Study group | Role | What they receive |
|---|---|---|
| gastric carcinoma | Experimental | 20 gastric carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 Receives: Drug: AL3810 |
| hepatocellular carcinoma | Experimental | 20 hepatocellular carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 Receives: Drug: AL3810 |
| Nasopharyngeal carcinoma | Experimental | 20 Nasopharyngeal carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 Receives: Drug: AL3810 |
What is being measured
The primary outcome is the main question the study is designed to answer.
AE
the number of patients with grade 3 and 4 AE according to CTC AE 4.03
Measured: through study completion, an average of 1 year
Secondary outcomes (6)
ORR
The proportion of patients who have observed overall remission (CR) or partial remission (PR) as the overall optimal remission based on the RECIST 1.1.
Measured: through study completion, an average of 1 year
AUC
Area under the plasma concentration versus time curve
Measured: up to 3 cycles(28 days/cycle)
Cmax
Peak Plasma Concentration
Measured: up to 3 cycles(28 days/cycle)
DoR
All patients with the best overall response to CR or PR were required to calculate the duration of the response. This time is the duration (progression or death, whichever occurs first) from the first decision to CR or PR to tumor progression or death (death for any cause)
Measured: through study completion, an average of 1 year
DCR
DCR refers to the percentage of patients who have achieved confirmation during the treatment of CR, confirmed PR and / or SD
Measured: through study completion, an average of 1 year
PFS
To the date of randomization to the date of the onset of the disease or the date of death (regardless of the cause of the death) (whichever is the earlier).
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2017
- Study start31 Aug 2017 (estimated)
- Primary completion31 Jan 2019 (estimated)
- Study completion30 Jun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haihe Biopharma Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03260179
- Sponsor's protocol ID
- CL1-80881-008
- Status last verified
- Aug 2017
- First submitted
- 20 Jul 2017
- Last updated
- 24 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhang Y, Luo F, Ma YX, Liu QW, Yang YP, Fang WF, Huang Y, Zhou T, Li J, Pan HM, Yang L, Qin SK, Zhao HY, Zhang L. A Phase Ib Study of Lucitanib (AL3810) in a Cohort of Patients with Recurrent and Metastatic Nasopharyngeal Carcinoma. Oncologist. 2022 Jun 8;27(6):e453-e462. doi: 10.1093/oncolo/oyab076.
PubMed 35445718
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase Ib, Study, to Determine Safety of Oral AL3810 in Patients With Locally Advanced or Metastatic Gastric, Hepatocellular or Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT03260179
- Acronym / sponsor ID
- CL1-80881-008
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Haihe Biopharma Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences
- Study start
- 31 Aug 2017 (estimated)
- Primary completion
- 31 Jan 2019 (estimated)
- Study completion
- 30 Jun 2019 (estimated)
- First posted
- 24 Aug 2017 (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 project intends to make a study of personalized medicine evaluation system establishment for liver cancer, gastric cancer and nasopharynx cancer to provide strong support for the development of Precision Medicine and personalized medicine for the patients of high-incidence-rates cancer in China.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| gastric carcinoma | Experimental | Drug: AL381020 gastric carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 |
| hepatocellular carcinoma | Experimental | Drug: AL381020 hepatocellular carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 |
| Nasopharyngeal carcinoma | Experimental | Drug: AL381020 Nasopharyngeal carcinoma patients were randomly divided into two groups: 4W on or 3w on/1w off, oral AL3810 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| AL3810Fasting,oral ,4w on or 3w on/1w off | Drug | gastric carcinoma |
| AL3810Fasting,oral ,4w on or 3w on/1w off | Drug | hepatocellular carcinoma |
| AL3810Fasting,oral ,4w on or 3w on/1w off | Drug | Nasopharyngeal carcinoma |
Primary outcome
AE
Time frame: through study completion, an average of 1 year
the number of patients with grade 3 and 4 AE according to CTC AE 4.03
6 secondary outcomes
ORR
Time frame: through study completion, an average of 1 year
AUC
Time frame: up to 3 cycles(28 days/cycle)
Cmax
Time frame: up to 3 cycles(28 days/cycle)
DoR
Time frame: through study completion, an average of 1 year
DCR
Time frame: through study completion, an average of 1 year
PFS
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2017.
- Derived from this study: PubMed 35445718Zhang Y, Luo F, Ma YX, Liu QW, Yang YP, Fang WF, Huang Y, Zhou T, Li J, Pan HM, Yang L, Qin SK, Zhao HY, Zhang L. A Phase Ib Study of Lucitanib (AL3810) in a Cohort of Patients with Recurrent and Metastatic Nasopharyngeal Carcinoma. Oncologist. 2022 Jun 8;27(6):e453-e462. doi: 10.1093/oncolo/oyab076.
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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.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AL3810 in people with Advanced Solid Tumor and Advanced/Metastatic Colorectal Cancer, run by Haihe Biopharma Co., Ltd. at 7 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 24 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
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 Qin Shu kui, MD (13905158713, qinsk@csco.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AE (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03260179, which also lists 1 linked publication.
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 24 Aug 2017.