Ovarian CancerPhase 2ANLOLANCT04566952
Anlotinib Combined With Dose-reduced Olaparib in Patients With Platinum-Sensitive Recurrent Ovarian Cancer
A Phase 2 study testing Anlotinib and Olaparib in people with Ovarian Cancer and Ovarian and Fallopian Tube Cysts and Neoplasms, run by Xiaoxiang Chen at 1 site in China.
Trial summary
PARP inhibitors have changed the treatment paradigm of ovarian cancer. Most patients using PARP(poly-ADP ribose polymerase) inhibitors will suffer different grades of adverse events(AEs), followed by dose reduction. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer, Ovarian and Fallopian Tube Cysts and Neoplasms, Neoplasms by Site
- What is being tested?
- Anlotinib and Olaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteChina
- Study dates
- 28 Oct 2020to 1 Oct 2023
- Phase
- Phase 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects join the study voluntarily and sign informed consent;
- Female subjects are older than 18 years;
- ECOG(Eastern Cooperative Oncology Group) physical status score is 0-1;
- Life expectancy≥3 months;
- Histologically confirmed FIGO(International Federation of Gynecology and Obstetrics ) III/IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; Participants must have high-grade serous or endometrioid histology;
- Platinum-sensitive recurrent ovarian cancer patients treated with olaparib as maintenance therapy according to NCCN(National Comprehensive Cancer Network) guideline and then suffered dose reduction due to adverse events. The reduction standard of olaparib following its instructions. Platinum-sensitive recurrent ovarian cancer is defined that patients are response to platinum-based chemotherapy and their platinum-free interval is greater than or equal to 6 months.
- Subjects have enough organ function: (1) Blood routine(without blood transfusion or hematopoietic stimulating factor within 7 days before screening): a.Hemoglobin(HB)≥90g/L; b.absolute neutrophil count(ANC)≥1.5*10^9/L; c.Platelet (PLT)≥80*10^9/L; (2) Blood biochemical examination(without blood or albumin transfusion within 7 days before screening): a. ALT( Alanine aminotransferase) and AST(Aspartate aminotransferase)≤2.5 times the upper limit of normal value and ALT (AST≤5 times the upper limit of normal value when liver/bone metastasis); b. total bilirubin≤1.5 times the upper limit of normal value; c.serum creatinine≤1.5 times the upper limit of normal value or creatinine clearance≥60ml/min; (3)Blood coagulation function: a. APTT(activated partial thromboplastin time ), INR(international normalized ratio) and PT≤1.5 times the upper limit of normal value; b.Doppler echocardiographic evaluation: left ventricular ejection fraction(LVEF)≥50%;
- Women of child-bearing age should have negative results of serum or urine pregnancy test within 7 days before recruited and must not be in lactation. Women are willing to adopt the appropriate methods of contraception during the trial and 6 months after last administration.
Who cannot join
- 1. Combined disease/history:
- Hemoptysis occurred within 3 months before admission (hemoptysis>50ml per day), or significantly clinical bleeding or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal bleeding or red blood cell positive at the baseline, or suffering from vasculitis, etc;
- Arteriovenous thrombosis events occurred within 6 months before grouping, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by venous catheterization due to prior chemotherapy) and pulmonary embolism, etc;
- Uncontrolled hypertension by antihypertensive drugs (systolic blood pressure>140 mmHg or diastolic blood pressure>90 mmHg); Myocardial infarction, severe/unstable angina pectoris, cardiac insufficiency above NYHA(New York Heart Association) 2, supraventricular or ventricular arrhythmias with clinical significance, and symptomatic congestive heart failure occurred within 6 months before grouping;
- Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (e.g. diabetes, pulmonary fibrosis and acute pneumonia);
- Renal insufficiency: urine routine indicates urinary protein≥++, or confirms 24-hour urinary protein≥1.0g;
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- History of live attenuated vaccine vaccination within 28 days before the first study medication or expected live attenuated vaccination during the study period;
- HIV infection or known AIDS; active hepatitis (hepatitis B, defined as HBV-DNA≥500 IU/ml; hepatitis C, defined as HCV-RNA higher than the lower limit of detection by analytical method) or co-infection of hepatitis B and hepatitis C;
- There were severe infections within 4 weeks before the first administration, including, but not limited to, bacteremia and severe pneumonia requiring hospitalization; active infections requiring systemic antibiotics treatment of grade CTCAE≥2 within 2 weeks before the first administration, or unexplained fever>38.5°C during the screening period/before the first administration (the researchers judged that fever caused by tumors could be included in the group); there was evidence of active tuberculosis infection within 1 year before administration;
- Any other malignant tumor has been diagnosed within 3 years before enrollment, except for fully treated basal cell carcinoma or squamous cell skin cancer or cervical carcinoma in situ;
- Major surgery was performed within 28 days before enrollment (tissue biopsy required for diagnosis and central venous catheterization via peripheral venipuncture was allowed);
- Subjects who have previously received or are prepared to receive allogeneic bone marrow transplantation or solid organ transplantation;
- Patients with peripheral neuropathy≥Grade 2; patients with active brain metastasis, carcinomatous meningitis, spinal cord compression, or diseases found in brain or leptomeninges by CT or MRI examination during screening (patients with brain metastasis who had completed treatment 14 days before admission and whose symptoms were stable can be enrolled in the group, but they should not suffer symptoms of cerebral hemorrhage confirmed by cranial MRI, CT or venography); (13）Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea, and intestinal obstruction with clinical significance; 2. Patients who are pregnant or lactation, or who plan to be pregnancy during study; 3. Other serious physical/mental disorders or laboratory abnormalities that may increase the risk of the study or interfere with the results of the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
JiangSu Cancer Hospital
Nanjing, Jangsu, 210009
Xiaoxiang Chen, PhD, +86 13851647229, cxxxxcyd@gmail.com
Jing Ni, MD, +86 13327833586, nijingwulin@126.com
About this study
Official title: A Prospective, Single-arm, Single-center, Exploratory Phase II Study to Evaluate the Efficacy and Safety of Anlotinib Combined With Dose-reduced Olaparib in Patients With Platinum-Sensitive Recurrent Ovarian Cancer
PARP inhibitors have changed the treatment paradigm of ovarian cancer. Most patients using PARP(poly-ADP ribose polymerase) inhibitors will suffer different grades of adverse events(AEs), followed by dose reduction. It has not been reported whether the dose-reduced olaparib as maintenance treatment have an impact on efficacy. Both PAOLA-1 and AVANOVA 2 studies showed that combined PARP inhibitors and antiangiogenic drugs have synergistic anti-tumor effect. Anlotinib is a novel multi-target tyrosine kinase inhibitor that can inhibit VEGFR(vascular endothelial growth factor receptor), FGFR(fibroblast growth factor receptor), PDGFR(platelet-derived growth factor receptor) α/β, c-Kit, and Ret. And anlotinib has been approved as orphan drug designations for treatment of ovarian cancer by FDA in 2015. Previous studies showed that anlotinib had manageable toxicity and promising antitumor effect. Our study is expected to investigate the efficacy and safety of anlotinib combined with dose-reduced olaparib as maintenance treatment in platinum-sensitive recurrent ovarian cancer patients.
Read the detailed description
This study is a single-arm, single-center, exploratory phase II study to observe the efficacy and safety of anlotinib combined with dose-reduced olaparib in patients with platinum-sensitive recurrent ovarian cancer, fallopian tube cancer and primary peritoneal cancer. We will enroll the subjects who are treated with olaparib as maintenance treatment followed by dose reduction due to adverse events. The primary end points are progression free survival and adverse events. The secondary end points include objective response rate, disease control rate, overall survival, time from enrollment to first subsequent treatment, quality of life.
- Conditions
- Ovarian Cancer, Ovarian and Fallopian Tube Cysts and Neoplasms, Neoplasms by Site, Neoplasms, Genital Neoplasms, Female, Urogenital Neoplasms
- Keywords
- Platinum-Sensitive Recurrent Ovarian Cancer, Anlotinib, Dose-reduced olaparib, Efficacy, Safety
- Medical subject headings
- Ovarian Neoplasms, Neoplasms, Neoplasms by Site, Genital Neoplasms, Female, Urogenital Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnlotinibDrug
Also called FOCUS V
Anlotinib will be treated with its minimum dose that is orally 8 mg daily on days 1-14 of a 21-days cycle.
OlaparibDrug
Also called Lynparza
Olaparib will be treated with a total daily dose of 450 or 300mg.
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib combined With dose-reduced olaparib | Experimental | Anlotinib-olaparib combination therapy until disease progression Receives: Drug: Anlotinib; Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the time in months from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death as assessed by RECIST1.1.
Measured: Through study completion, an average of 1 year
Adverse events (AEs)
Number of participants with treatment-related adverse events as assessed by CTCAE 5.0 to further describe safety and assess toxicities encountered with the use of the proposed treatment regimen in participants.
Measured: Through study completion, an average of 1 year
Secondary outcomes (5)
Overall Response Rate (ORR)
ORR is defined as the proportion of participants achieving complete response (CR) or partial response (PR) as assessed by RECIST1.1.
Measured: Through study completion, an average of 1 year
Disease Control Rate (DCR)
DCR is defined as the proportion of participants achieving complete response (CR), partial response (PR) or stable disease (SD) according to RECIST1.1.
Measured: Through study completion, an average of 1 year
Overall survival (OS)
OS is defined as time from randomisation to the first occurrence of death from any cause.
Measured: Through study completion, an average of 1 year
Time from enrollment to first subsequent treatment (TFST)
TFST is defined as time from enrollment to first subsequent treatment.
Measured: Through study completion, an average of 1 year
Quality of Life(QoL)
EORTC QLQ-C30(European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30) is used to evaluate the quality of life. Scores range from 0 to 100, with higher scores indicating better health-related quality of life
Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, 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 posted28 Sep 2020
- Study start28 Oct 2020
- Primary completion1 Mar 2023 (estimated)
- Study completion1 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiaoxiang Chen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xiaoxiang Chen, Jiangsu Cancer Institute & Hospital
- Investigators
- Xiaoxiang Chen, MD,PhD, Study chair, Jiangsu Cancer Institute & Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04566952
- Sponsor's protocol ID
- JiangsuCH002
- Acronym
- ANLOLA
- Status last verified
- Oct 2020
- First submitted
- 24 Sep 2020
- Last updated
- 30 Oct 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Contact Prof. Chen for primary data
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Single-arm, Single-center, Exploratory Phase II Study to Evaluate the Efficacy and Safety of Anlotinib Combined With Dose-reduced Olaparib in Patients With Platinum-Sensitive Recurrent Ovarian Cancer
- ClinicalTrials.gov ID
- NCT04566952
- Acronym / sponsor ID
- ANLOLA / JiangsuCH002
- Conditions
- Ovarian Cancer, Ovarian and Fallopian Tube Cysts and Neoplasms, Neoplasms by Site, Neoplasms, Genital Neoplasms, Female, Urogenital Neoplasms
- Keywords
- Platinum-Sensitive Recurrent Ovarian Cancer, Anlotinib, Dose-reduced olaparib, Efficacy, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Xiaoxiang ChenUniversity, hospital or other
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 1 Mar 2023 (estimated)
- Study completion
- 1 Oct 2023 (estimated)
- First posted
- 28 Sep 2020 (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.
PARP inhibitors have changed the treatment paradigm of ovarian cancer. Most patients using PARP(poly-ADP ribose polymerase) inhibitors will suffer different grades of adverse events(AEs), followed by dose reduction. It has not been reported whether the dose-reduced olaparib as maintenance treatment have an impact on efficacy. Both PAOLA-1 and AVANOVA 2 studies showed that combined PARP inhibitors and antiangiogenic drugs have synergistic anti-tumor effect. Anlotinib is a novel multi-target tyrosine kinase inhibitor that can inhibit VEGFR(vascular endothelial growth factor receptor), FGFR(fibroblast growth factor receptor), PDGFR(platelet-derived growth factor receptor) α/β, c-Kit, and Ret. And anlotinib has been approved as orphan drug designations for treatment of ovarian cancer by FDA in 2015. Previous studies showed that anlotinib had manageable toxicity and promising antitumor effect. Our study is expected to investigate the efficacy and safety of anlotinib combined with dose-reduced olaparib as maintenance treatment in platinum-sensitive recurrent ovarian cancer patients.
Detailed description
This study is a single-arm, single-center, exploratory phase II study to observe the efficacy and safety of anlotinib combined with dose-reduced olaparib in patients with platinum-sensitive recurrent ovarian cancer, fallopian tube cancer and primary peritoneal cancer. We will enroll the subjects who are treated with olaparib as maintenance treatment followed by dose reduction due to adverse events. The primary end points are progression free survival and adverse events. The secondary end points include objective response rate, disease control rate, overall survival, time from enrollment to first subsequent treatment, quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anlotinib combined With dose-reduced olaparib | Experimental | Drug: Anlotinib, Drug: OlaparibAnlotinib-olaparib combination therapy until disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subjects join the study voluntarily and sign informed consent;
- Female subjects are older than 18 years;
- ECOG(Eastern Cooperative Oncology Group) physical status score is 0-1;
- Life expectancy≥3 months;
- Histologically confirmed FIGO(International Federation of Gynecology and Obstetrics ) III/IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; Participants must have high-grade serous or endometrioid histology;
Key exclusion criteria (13 listed)
- Hemoptysis occurred within 3 months before admission (hemoptysis>50ml per day), or significantly clinical bleeding or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal bleeding or red blood cell positive at the baseline, or suffering from vasculitis, etc;
- Arteriovenous thrombosis events occurred within 6 months before grouping, such as cerebrovascular accident (including temporary ischemic attack), deep venous thrombosis (except venous thrombosis caused by venous catheterization due to prior chemotherapy) and pulmonary embolism, etc;
- Uncontrolled hypertension by antihypertensive drugs (systolic blood pressure>140 mmHg or diastolic blood pressure>90 mmHg); Myocardial infarction, severe/unstable angina pectoris, cardiac insufficiency above NYHA(New York Heart Association) 2, supraventricular or ventricular arrhythmias with clinical significance, and symptomatic congestive heart failure occurred within 6 months before grouping;
- Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (e.g. diabetes, pulmonary fibrosis and acute pneumonia);
- Renal insufficiency: urine routine indicates urinary protein≥++, or confirms 24-hour urinary protein≥1.0g;
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 |
|---|---|---|
| AnlotinibAlso: FOCUS VAnlotinib will be treated with its minimum dose that is orally 8 mg daily on days 1-14 of a 21-days cycle. | Drug | Anlotinib combined With dose-reduced olaparib |
| OlaparibAlso: LynparzaOlaparib will be treated with a total daily dose of 450 or 300mg. | Drug | Anlotinib combined With dose-reduced olaparib |
Primary outcome
Progression Free Survival (PFS)
Time frame: Through study completion, an average of 1 year
PFS is defined as the time in months from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death as assessed by RECIST1.1.
Adverse events (AEs)
Time frame: Through study completion, an average of 1 year
Number of participants with treatment-related adverse events as assessed by CTCAE 5.0 to further describe safety and assess toxicities encountered with the use of the proposed treatment regimen in participants.
5 secondary outcomes
Overall Response Rate (ORR)
Time frame: Through study completion, an average of 1 year
Disease Control Rate (DCR)
Time frame: Through study completion, an average of 1 year
Overall survival (OS)
Time frame: Through study completion, an average of 1 year
Time from enrollment to first subsequent treatment (TFST)
Time frame: Through study completion, an average of 1 year
Quality of Life(QoL)
Time frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, 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 30 Oct 2020.
- Individual participant dataSharing planned: No. Contact Prof. Chen for primary data
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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.
Xiaoxiang Chen, MD,PhD study chair
Jiangsu Cancer Institute & Hospital
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 Anlotinib and Olaparib in people with Ovarian Cancer and Ovarian and Fallopian Tube Cysts and Neoplasms, run by Xiaoxiang Chen 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 8 inclusion and 13 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 30 Oct 2020. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaoxiang Chen, MD,PhD (+86 13851647229, cxxxxcyd@gmail.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: Through study completion, an average of 1 year). The study lists 2 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 30 Oct 2020.