NSCLC Stage IVPhase 2PCANCT04136535
Pemetrexed and Carboplatin With or Without Anlotinib Hydrochloride for Osimertinib-resistant Non-squamous NSCLC
A Phase 2 study testing Pemetrexed, Carboplatin and Anlotinib in people with NSCLC Stage IV, run by Fudan University at 1 site in China.
Trial summary
Evaluate the efficacy and safety of Anlotinib Hydrochloride in combination with Pemetrexed and Carboplatin versus Pemetrexed and Carboplatin for advanced or locally-advanced Osimertinib-resistant non-squamous non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NSCLC Stage IV
- What is being tested?
- Pemetrexed, Carboplatin and Anlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteChina
- Study dates
- 18 Nov 2021to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 18 Years to 75 Years patients voluntarily participate in this study, signed and dated informed consent with good compliance and follow-up; 2. Confirmed as locally advanced and / or metastatic non-squamous non-small cell lung cancer (NSCLC) by cytology or histology, the diagnosis should be completed at least 6 months after the end of chemotherapy if adjuvant chemotherapy and / or neoadjuvant chemotherapy received (diagnosis based on sputum smear is not accepted) ; 3. Presence of EGFR activating mutations and previously disease progression to Osimertinib (previously treated with 1st / 2nd generation EGFR-TKI or not)； 4. At least one target lesion that has accurate measurement by magnetic resonance imaging (MRI) or computed tomography (CT) (conventional CT≥20 mm or spiral CT≥10 mm) in at least 1 direction; 5. Life expectancy is at least 3 months; 6. ECOG PS Scoring: 0~1 point; 8. The main organs function are normally, the following criteria are met:
- Blood routine examination criteria (no blood transfusion and blood products within 14 days, no correction by G-CSF and other hematopoietic stimuli):
- hemoglobin (HB) ≥90g/L ii) neutrophil absolute (ANC) ≥1.5×109/L iii) platelet (PLT) ≥80×109/L Biochemical tests meet the following criteria i) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.25 ULN or creatinine clearance (CCr)≥45mL/min (Cockcroft-Gault formula).
- 9.Female patients of childbearing age agree that contraceptive measures must be used within the study period and within 8 weeks after the end of the study drug treatment. The serum or urine test indicates unpregnancy within 7 days prior to the study. Male patients agree to have contraceptive use during the study period and within 8 weeks after the end of the study period or have had surgical sterilization.
Who cannot join
- Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer) and lung adenosquamous carcinoma mixed with squamous carcinoma;
- Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 21 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms);
- Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel and the distance between tumor and bronchial tree is ≤ 2 cm; or there is a significant pulmonary cavity or necrotizing tumor;
- Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg after optimal medical treatment);
- Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) <50%;
- Abnormal blood coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
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- Urine routine test protein ≥++, and confirmed 24 hours urine protein> 1.0 g;
- There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma;
- Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment;
- Long-term unhealed wounds or fractures;
- Serious infection (≥CTC AE Level 2 infection) requiring systemic antibiotics;
- decompensated diabetes or other ailments treated with high doses of glucocorticoids;
- Active or chronic hepatitis C or/and hepatitis B infection;
- Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
- Patients have undergone major surgery within 4 weeks before enrollment or have severe trauma, fracture and ulcer;
- Severe weight loss (greater than 10%) within 6 weeks prior to enrollment;
- Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis;
- Events of venous/ arterious thrombosis occurring within the first 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- Patients have contraindication to platinum drugs (Cisplatin/Carboplatin) and cytotoxic drug (Pemetrexed);
- Patients have anaphylactic reaction due to Anlotinib Hydrochloride or the excipient in investigational drug.
- Planned for systemic anti-tumor therapy during the study period or within 4 weeks prior to enrollment, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or use mitomycin C within 6 weeks prior to receiving investigational drug). Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeks before enrollment or limited-field radiotherapy was performed for planned tumor lesions within 2 weeks before enrollment.
- Patients with other situations which are not suitable for the study according to the researchers.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Caner hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Uninon Medical college
Shenzhen, shenzhen, 518116
Chang j hua, PD, 18017312689, changjianhua@163.com
About this study
Official title: A Multicenter, Randomized, Phase II Study of Pemetrexed and Carboplatin With or Without Anlotinib Hydrochloride for Advanced or Locally-advanced Osimertinib-resistant Non-squamous Non-small Cell Lung Cancer (ALTER-L031)
Evaluate the efficacy and safety of Anlotinib Hydrochloride in combination with Pemetrexed and Carboplatin versus Pemetrexed and Carboplatin for advanced or locally-advanced Osimertinib-resistant non-squamous non-small cell lung cancer.
Read the detailed description
Anlotinib Hydrochloride in combination with Pemetrexed and Carboplatin use 4 cycles,then continue pem and anlotinib until PD
Pemetrexed and Carboplatin use 4 cycles,then continue pem until PD
TO see the different of PFS and OS and safety between the two group
- Conditions
- NSCLC Stage IV
- Being tested
- Pemetrexed, Carboplatin, Anlotinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemetrexedDrug
Pemetrexed，500mg/m²，ivgtt ，d1，q3w
CarboplatinDrug
Carboplatin，AUC 5.0，ivgtt，d1，q3w，
AnlotinibDrug
Anlotinib ，12 mg，po，qd，d1-14，q3w；
| Study group | Role | What they receive |
|---|---|---|
| Pemetrexed and Carboplatin with Anlotinib | Experimental | Pemetrexed and Carboplatin with Anlotinib Receives: Drug: Pemetrexed; Drug: Carboplatin; Drug: Anlotinib |
| Pemetrexed and Carboplatin without Anlotinib | Active comparator | Pemetrexed and Carboplatin without Anlotinib Receives: Drug: Pemetrexed; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Progress free survival
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2019
- Study start18 Nov 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (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 NSCLC Stage IVStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chang Jian Hua, Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
- Investigators
- chang j hua, PD, Principal investigator, PI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04136535
- Sponsor's protocol ID
- ALTER-L031
- Acronym
- PCA
- Status last verified
- Jul 2025
- First submitted
- 14 Oct 2019
- Last updated
- 22 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
PubMed 27959700
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Phase II Study of Pemetrexed and Carboplatin With or Without Anlotinib Hydrochloride for Advanced or Locally-advanced Osimertinib-resistant Non-squamous Non-small Cell Lung Cancer (ALTER-L031)
- ClinicalTrials.gov ID
- NCT04136535
- Acronym / sponsor ID
- PCA / ALTER-L031
- Conditions
- NSCLC Stage IV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 18 Nov 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Oct 2019 (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.
Evaluate the efficacy and safety of Anlotinib Hydrochloride in combination with Pemetrexed and Carboplatin versus Pemetrexed and Carboplatin for advanced or locally-advanced Osimertinib-resistant non-squamous non-small cell lung cancer.
Detailed description
Anlotinib Hydrochloride in combination with Pemetrexed and Carboplatin use 4 cycles,then continue pem and anlotinib until PD
Pemetrexed and Carboplatin use 4 cycles,then continue pem until PD
TO see the different of PFS and OS and safety between the two group
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pemetrexed and Carboplatin with Anlotinib | Experimental | Drug: Pemetrexed, Drug: Carboplatin, Drug: AnlotinibPemetrexed and Carboplatin with Anlotinib |
| Pemetrexed and Carboplatin without Anlotinib | Active comparator | Drug: Pemetrexed, Drug: CarboplatinPemetrexed and Carboplatin without Anlotinib |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 1. 18 Years to 75 Years patients voluntarily participate in this study, signed and dated informed consent with good compliance and follow-up; 2. Confirmed as locally advanced and / or metastatic non-squamous non-small cell lung cancer (NSCLC) by cytology or histology, the diagnosis should be completed at least 6 months after the end of chemotherapy if adjuvant chemotherapy and / or neoadjuvant chemotherapy received (diagnosis based on sputum smear is not accepted) ; 3. Presence of EGFR activating mutations and previously disease progression to Osimertinib (previously treated with 1st / 2nd generation EGFR-TKI or not)； 4. At least one target lesion that has accurate measurement by magnetic resonance imaging (MRI) or computed tomography (CT) (conventional CT≥20 mm or spiral CT≥10 mm) in at least 1 direction; 5. Life expectancy is at least 3 months; 6. ECOG PS Scoring: 0~1 point; 8. The main organs function are normally, the following criteria are met:
- Blood routine examination criteria (no blood transfusion and blood products within 14 days, no correction by G-CSF and other hematopoietic stimuli):
- hemoglobin (HB) ≥90g/L ii) neutrophil absolute (ANC) ≥1.5×109/L iii) platelet (PLT) ≥80×109/L Biochemical tests meet the following criteria i) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.25 ULN or creatinine clearance (CCr)≥45mL/min (Cockcroft-Gault formula).
- 9.Female patients of childbearing age agree that contraceptive measures must be used within the study period and within 8 weeks after the end of the study drug treatment. The serum or urine test indicates unpregnancy within 7 days prior to the study. Male patients agree to have contraceptive use during the study period and within 8 weeks after the end of the study period or have had surgical sterilization.
Key exclusion criteria (22 listed)
- Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer) and lung adenosquamous carcinoma mixed with squamous carcinoma;
- Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 21 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms);
- Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel and the distance between tumor and bronchial tree is ≤ 2 cm; or there is a significant pulmonary cavity or necrotizing tumor;
- Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg after optimal medical treatment);
- Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates 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 |
|---|---|---|
| PemetrexedPemetrexed，500mg/m²，ivgtt ，d1，q3w | Drug | Pemetrexed and Carboplatin with Anlotinib, Pemetrexed and Carboplatin without Anlotinib |
| CarboplatinCarboplatin，AUC 5.0，ivgtt，d1，q3w， | Drug | Pemetrexed and Carboplatin with Anlotinib, Pemetrexed and Carboplatin without Anlotinib |
| AnlotinibAnlotinib ，12 mg，po，qd，d1-14，q3w； | Drug | Pemetrexed and Carboplatin with Anlotinib |
Primary outcome
PFS
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Progress free survival
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2025.
- Background: PubMed 27959700Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
- 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.
chang j hua, PD principal investigator
PI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pemetrexed, Carboplatin and Anlotinib in people with NSCLC Stage IV, run by Fudan University 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 4 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 22 Jul 2025. 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 phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact chang J hua, PD (18017312689, changjianhua@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months). 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 NCT04136535, 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 22 Jul 2025.