Recurrent Nasopharyngeal CarcinomaPhase 1/2NCT03639467
Study of Anlotinib Combined With Gemcitabine/Cisplatin in Advanced Nasopharyngeal Carcinoma
A Phase 1/2 study testing Anlotinib plus gemcitabine/cisplatin in people with Recurrent Nasopharyngeal Carcinoma and Metastatic Nasopharyngeal Carcinoma, run by Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
Gemcitabine plus cisplatin (GC) is more effective than fluorouracil plus cisplatin in the treatment of recurrent or metastatic NPC (R/M-NPC). GC is the standard first-line chemotherapy regimen for this population. However, the median progression-free survival was only 7 months for GC regimen. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Recurrent Nasopharyngeal Carcinoma, Metastatic Nasopharyngeal Carcinoma
- What is being tested?
- Anlotinib plus gemcitabine/cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 18 Sep 2018to 15 Aug 2023
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years to 70 years.
- Histological/cytological confirmation of NPC.
- Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) or recurrent NPC that is not amenable for local regional treatment or curative treatment.
- Patients did not receive systemic chemotherapy for recurrent or metastatic disease, except for prior induction, concurrent, or adjuvant chemotherapy that was completed > 6 months prior to registration. Prior radiotherapy or chemoradiotherapy should be completed > 6 months prior to registration;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
- Life expectancy of more than 12 weeks.
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- At least one measurable lesion according to RECIST 1.1 which has not received radiotherapy ≥ 3 months.
- Adequate hepatic, renal, heart, and hematologic functions: absolute neutrophil count (ANC) ≥ 1.5×109/L, platelet count (PLT) ≥ 100×109/L, hemoglobin (HB) ≥ 90 g/L, total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN), alternate aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3×ULN (or ≤ 5×ULN in patients with liver metastases), Serum Cr ≤ 1×ULN, Cr clearance ≥ 60 mL/min, international normalized ratio (INR) < 1.5 or prothrombin time (PT) < ULN+4s or activated partial thromboplastin time (APTT) < 1.5×ULN, proteinuria < (++) or urinary protein ≤ 1.0 g/24 hrs;
- For women of child-bearing age, the pregnancy test results (serum or urine) within 7 days before enrolment must be negative. They will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men (previous surgical sterilization accepted), will take appropriate methods for contraception during the study until the 8th week post the last administration of study drug.
- Signed informed consent.
Who cannot join
- Other malignancy within the past five years other than basal cell skin cancer, or carcinoma in situ of the cervix;
- Factors affecting the oral medication (e.g. inability to swallow, chronic diarrhea and intestinal obstruction);
- Major injuries and/or surgery ≤ 4 weeks prior to registration with incomplete wound healing.
- Patients with poor-controlled arterial hypertension (systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mm Hg) despite standard medical management;
- Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias. Grade III-IV cardiac insufficiency according to New York Heart Association (NYHA) criteria or echocardiography check: left ventricular ejection fraction (LVEF)<50%;
- History of clinically significant haemoptysis ≤ 2 months (more than half of one tea spoon of fresh blood per day) prior to registration. Coagulation disfunction, hemorrhagic tendency or receiving anticoagulant therapy;
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- History of clinically relevant major bleeding event (e.g. gastrointestinal hemorrhage, bleeding ulcer, occult blood ≥ (++), and vasculitis) ≤ 3 months prior to randomization;
- Patients who have active brain metastases or leptomeningeal disease. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation ending at least 3 weeks prior to randomization, or after surgical resection performed at least 3 weeks prior to randomization. No evidence of Grade greater than or equal to 1 central nervous system (CNS) hemorrhage based on pretreatment CT or MRI scan; Centrally located tumors of local invasion of major blood vessels, or distinct interstitial lung disease by the chest radiographic findings (CT or MRI);
- Treatment with other investigational drugs or other anti-cancer therapy;
- Previous therapy with anti-angiogenic drugs (such as anlotinib, apatinib, bevacizumab, endostar, etc.)
- Treatment in another investigational trial ≤ 4 weeks prior to registration;
- History of hypersensitivity to anlotinib, gemcitabine, cisplatin and/or the excipients of the trial drugs;
- Active or chronic hepatitis C and/or B infection, or other active uncontrolled infection;
- History of immunodeficiency disease (including HIV positive), concurrent acquired or congenital immunodeficiency syndrome, or history of organ transplantation;
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months prior to registration;
- History of arterial or venous thromboembolic events (e.g. cerebrovascular accident, cardiovascular accident, deep venous thrombosis and pulmonary embolism) ≤ 12 months prior to randomization;
- Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study;
- History of mental diseases;
- Other conditions regimented at investigators' discretion.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
National Cancer Center/Cancer Hospitial,Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, 100021
Yuankai Shi, MD, +86-10-87788293, syuankaipumc@126.com
About this study
Official title: Phase Ib / II Study of Anlotinib Combined With Gemcitabine/Cisplatin in Previous Untreated Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
Gemcitabine plus cisplatin (GC) is more effective than fluorouracil plus cisplatin in the treatment of recurrent or metastatic NPC (R/M-NPC). GC is the standard first-line chemotherapy regimen for this population. However, the median progression-free survival was only 7 months for GC regimen. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR2、VEGFR3、PDGFRβ and c-Kit, which has strong effect of anti-angiogenesis. This study is aim to evaluate the efficacy and safety of the combination regimen of anlotinib plus GC as first-line treatment for R/M-NPC.
Read the detailed description
In the phase Ib portion, an escalated dose cohort is recruited to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of anlotinib when given in combination with gemcitabine/cisplatin. The phase II portion is designed to characterize the efficacy and safety of the combination therapy in previous untreated patients with R/M-NPC.
- Being tested
- Anlotinib plus gemcitabine/cisplatin
- Keywords
- anlotinib, nasopharyngeal carcinoma, gemcitabine, cisplatin
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anlotinib plus gemcitabine/cisplatinDrug
In the phase Ib portion, patients received dose escalation of anlotinb (from 8mg to 12mg orally once daily on days 1-14 of a 21-day) in combination with fixed dose of gemcitabine (1000mg/m2 intravenously on days 1 and 8) and cisplatin (80mg/m2 intravenously on day 1) every 3 weeks.
In the phase II portion, patients received anlotinb at recommended phase II dose determined in the phase Ib portion, in combination with fixed dose of gemcitabine and cisplatin every 3 weeks.
The combination of anlotinib plus gemcitabine / cisplatin was repeated every 3 weeks for up to six cycles. Patients with disease control (defined as a complete response, a partial response, or stable disease) continue to receive anlotinb until disease progression or unacceptable toxic effects, whichever occurred first.
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib plus gemcitabine/cisplatin | Experimental | In the phase Ib portion, patients received dose escalation of anlotinb (from 8mg to 12mg orally once daily on days 1-14 of a 21-day) in combination with fixed dose of gemcitabine (1000mg/m2 intravenously on days 1 and 8) and cisplatin (80mg/m2 intravenously on day 1) every 3 weeks.
In the phase II portion, patients received anlotinb at recommended phase II dose determined in the phase Ib portion, in combination with fixed dose of gemcitabine and cisplatin every 3 weeks.
The combination of anlotinib plus gemcitabine / cisplatin was repeated every 3 weeks for up to six cycles. Patients with disease control (defined as a complete response, a partial response, or stable disease) continue to receive anlotinb until disease progression or unacceptable toxic effects, whichever occurred first. Receives: Drug: Anlotinib plus gemcitabine/cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
From date of enrollment until the date of first documented progression or date of death from any cause,whichever came first
Measured: up to 3 years
Secondary outcomes (3)
Objective Response Rate (ORR)
The objective Response Rate of anlotinib plus gemcitabine/cisplatin in Previous Untreated Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
Measured: up to 3 years
Overall survival (OS)
OS of of anlotinib plus gemcitabine/cisplatin in previous untreated patients with recurrent/metastatic Nasopharyngeal Carcinoma
Measured: up to 3 years
Incidence of treatment-emergent adverse events (safety and tolerability)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2018
- Study start18 Sep 2018 (estimated)
- Primary completion22 Aug 2021 (estimated)
- Study completion15 Aug 2023 (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 Recurrent Nasopharyngeal CarcinomaStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shi Yuankai, Chinese Academy of Medical Sciences
- Investigators
- Yuankai Shi, MD, Principal investigator, ChineseAMS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03639467
- Sponsor's protocol ID
- NCC201807021
- Status last verified
- Sep 2018
- First submitted
- 15 Aug 2018
- Last updated
- 18 Sep 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13.
PubMed 29438373
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib / II Study of Anlotinib Combined With Gemcitabine/Cisplatin in Previous Untreated Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT03639467
- Acronym / sponsor ID
- NCC201807021
- Keywords
- anlotinib, nasopharyngeal carcinoma, gemcitabine, cisplatin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 18 Sep 2018 (estimated)
- Primary completion
- 22 Aug 2021 (estimated)
- Study completion
- 15 Aug 2023 (estimated)
- First posted
- 21 Aug 2018 (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.
Gemcitabine plus cisplatin (GC) is more effective than fluorouracil plus cisplatin in the treatment of recurrent or metastatic NPC (R/M-NPC). GC is the standard first-line chemotherapy regimen for this population. However, the median progression-free survival was only 7 months for GC regimen. Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR2、VEGFR3、PDGFRβ and c-Kit, which has strong effect of anti-angiogenesis. This study is aim to evaluate the efficacy and safety of the combination regimen of anlotinib plus GC as first-line treatment for R/M-NPC.
Detailed description
In the phase Ib portion, an escalated dose cohort is recruited to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of anlotinib when given in combination with gemcitabine/cisplatin. The phase II portion is designed to characterize the efficacy and safety of the combination therapy in previous untreated patients with R/M-NPC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anlotinib plus gemcitabine/cisplatin | Experimental | Drug: Anlotinib plus gemcitabine/cisplatinIn the phase Ib portion, patients received dose escalation of anlotinb (from 8mg to 12mg orally once daily on days 1-14 of a 21-day) in combination with fixed dose of gemcitabine (1000mg/m2 intravenously on days 1 and 8) and cisplatin (80mg/m2 intravenously on day 1) every 3 weeks. In the phase II portion, patients received anlotinb at recommended phase II dose determined in the phase Ib portion, in combination with fixed dose of gemcitabine and cisplatin every 3 weeks. The combination of anlotinib plus gemcitabine / cisplatin was repeated every 3 weeks for up to six cycles. Patients with disease control (defined as a complete response, a partial response, or stable disease) continue to receive anlotinb until disease progression or unacceptable toxic effects, whichever occurred first. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 18 years to 70 years.
- Histological/cytological confirmation of NPC.
- Primarily metastatic (stage IVB as defined by the International Union against Cancer and American Joint Committee on Cancer staging system for NPC, eighth edition) or recurrent NPC that is not amenable for local regional treatment or curative treatment.
- Patients did not receive systemic chemotherapy for recurrent or metastatic disease, except for prior induction, concurrent, or adjuvant chemotherapy that was completed > 6 months prior to registration. Prior radiotherapy or chemoradiotherapy should be completed > 6 months prior to registration;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
Key exclusion criteria (19 listed)
- Other malignancy within the past five years other than basal cell skin cancer, or carcinoma in situ of the cervix;
- Factors affecting the oral medication (e.g. inability to swallow, chronic diarrhea and intestinal obstruction);
- Major injuries and/or surgery ≤ 4 weeks prior to registration with incomplete wound healing.
- Patients with poor-controlled arterial hypertension (systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mm Hg) despite standard medical management;
- Suffered from grade II or above myocardial ischemia or myocardial infarction, uncontrolled arrhythmias. Grade III-IV cardiac insufficiency according to New York Heart Association (NYHA) criteria or echocardiography check: left ventricular ejection fraction (LVEF)<50%;
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 |
|---|---|---|
| Anlotinib plus gemcitabine/cisplatinIn the phase Ib portion, patients received dose escalation of anlotinb (from 8mg to 12mg orally once daily on days 1-14 of a 21-day) in combination with fixed dose of gemcitabine (1000mg/m2 intravenously on days 1 and 8) and cisplatin (80mg/m2 intravenously on day 1) every 3 weeks. In the phase II portion, patients received anlotinb at recommended phase II dose determined in the phase Ib portion, in combination with fixed dose of gemcitabine and cisplatin every 3 weeks. The combination of anlotinib plus gemcitabine / cisplatin was repeated every 3 weeks for up to six cycles. Patients with disease control (defined as a complete response, a partial response, or stable disease) continue to receive anlotinb until disease progression or unacceptable toxic effects, whichever occurred first. | Drug | Anlotinib plus gemcitabine/cisplatin |
Primary outcome
Progression-free survival (PFS)
Time frame: up to 3 years
From date of enrollment until the date of first documented progression or date of death from any cause,whichever came first
3 secondary outcomes
Objective Response Rate (ORR)
Time frame: up to 3 years
Overall survival (OS)
Time frame: up to 3 years
Incidence of treatment-emergent adverse events (safety and tolerability)
Time frame: up to 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
- Results publication: PubMed 29438373Han B, Li K, Zhao Y, Li B, Cheng Y, Zhou J, Lu Y, Shi Y, Wang Z, Jiang L, Luo Y, Zhang Y, Huang C, Li Q, Wu G. Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302). Br J Cancer. 2018 Mar 6;118(5):654-661. doi: 10.1038/bjc.2017.478. Epub 2018 Feb 13.
- Individual participant dataSharing planned: Undecided
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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.
Yuankai Shi, MD principal investigator
ChineseAMS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Anlotinib plus gemcitabine/cisplatin in people with Recurrent Nasopharyngeal Carcinoma and Metastatic Nasopharyngeal Carcinoma, run by Chinese Academy of Medical Sciences at 1 site in China.
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 10 inclusion and 19 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 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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 Yuankai Shi, MD (+86 10 87788293, syuankaipumc@126.com;), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: up to 3 years). 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 NCT03639467, 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 18 Sep 2018.