Concurrent Radiochemotherapy Plus Anlotinib for Locally Advanced Cervical Cancer

NCT04772001 | Unknown

• 1 other identifier: CC-RT-ALTER-01
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

To observe the efficacy and safety of hydrochloride anlotinib combined with concurrent radiochemotherapy for patients with FIGO stage IB3 and IIA2-IVA cervical cancer. Patient characteristics, image and genetic information of tumor, microbial sample of tumor microenvironment and biomarker in the blood sample will be collected and analysis by multi-omics and bioinformatic technology. Aim to provide a new treatment module for cervical cancer.

Conditions

Uterine Cervical Neoplasms; Chemoradiotherapy; Angiogenesis

Keywords

Uterine Cervical Neoplasms; Chemoradiotherapy; Anlotinib

Outcome Measures

Primary Outcomes (1)

• 3 years disease free survival rate

  Proportion of participants without tumor recurrence or death at 3 years from enrollment

  3 years from enrollment

Secondary Outcomes (9)

• Adverse events

  From enrollment to 90 days after treatment finish

• 3 years overall survival rate

  3 years from enrollment

• Objective response rate

  5 years from enrollment

• Disease control rate

  5 years from enrollment

• 5 years progression free survival rate

  5 years from enrollment

Study Arms (1)

CCRT+Anlotinib

EXPERIMENTAL

Classical chemoradiotherapy will be conducted by clinical routine method. Radiation will be given by external beam of 45Gy total dose and 3D-brachytherapy of 30Gy/5F or 28Gy/4F. Duration of radiotherapy will be no more than 8 weeks. Concurrent chemotherapy will be administrated weekly during radiation for a total of 5-6 doses. Cisplatin of 40mg/m2 will be the most preferred regime and for patients with intolerable toxicity of cisplatin, carboplatin of AUC 2 will be the alternative drug. Hydrochloride anlotinib will be orally taken daily at a dose level of 12mg for 14 days. Then rest for 7 days and start a new cycles for a total of 3 cycles. First capsule of anlotinib will be taken 7 days before the first radiation.

Drug: Hydrochloride anlotinib; Drug: cis Platinum/carboplatin; Radiation: External beam radiotherapy and brachytherapy

Interventions

Hydrochloride anlotinib DRUG

Hydrochloride anlotinib is a small molecular anti-angiogenesis drug with multiple targets. It will be taken at a starting dose of 12 mg for 14 days. Then participants will rest for 7 days and start a new cycles. At most of 3 cycles will be administrated. If intolerable toxicity happen, dosage of 10mg or 8mg will be taken.

CCRT+Anlotinib

cis Platinum/carboplatin DRUG

Concurrent chemotherapy will be administrated weekly during radiation for a total of 5-6 doses. Cisplatin of 40mg/m2 will be the most preferred regime. For patients with intolerable toxicity of cisplatin, carboplatin of AUC 2 will be the alternative drug.

CCRT+Anlotinib

External beam radiotherapy and brachytherapy RADIATION

Radiation will be given by external beam of 45Gy total dose and 3D-brachytherapy of 30Gy/5F or 28Gy/4F. Duration of radiotherapy will be no more than 8 weeks.

CCRT+Anlotinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old and ≤75 years old;
• ECOG PS score 0-2 points;
• After pathological examination, it is clear that it is cervical cancer, the pathological types include squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma;
• The staging conforms to the definitions of IB3 and IIA2-IVA in FIGO2018;
• The expected survival period is ≥6 months;
• The lesion meets the requirements of RECIST 1.1 for evaluable lesions;
• Have not received any form of anti-tumor treatment before joining the group (except for partial cervical biopsy resection);
• Expect to tolerate radiotherapy;
• It is expected to tolerate concurrent chemotherapy with platinum drugs;
• It is expected to tolerate oral Anlotinib treatment;
• The sitting blood pressure at rest is less than the normal high value (\<140/90mmHg), or the average blood pressure of the 24-hour ambulatory blood pressure monitoring is less than the normal high value (\<140/90mmHg), regardless of whether you are taking antihypertensive drugs or not;
• Hematology indicators meet (no blood transfusion and no correction with hematopoietic stimulating factor drugs within 7 days before screening): white blood cell count (WBC) ≥3.5×109/L and ≤10×109/L, neutrophil count ( ANC) ≥1.5×109/L, platelet (PLT) ≥125×109/L, hemoglobin (Hb) ≥90g/L;
• The liver function index meets: ALT and AST≤2.5 times high normal value (ULN), bilirubin≤1.5×ULN, albumin≥35g/L;
• The coagulation function index meets (not receiving anticoagulation or drug hemostasis treatment): PT and APTT ≤ 1.5×ULN, and INR ≤ 1.5 ULN;
• Renal function indicators meet: urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN and creatinine clearance ≥60 mL/min (Cockcroft-Gault formula), urine protein \<2+ or 24-hour urine protein quantitative \<1g

You may not qualify if:

• Any unstable systemic disease, including but not limited to active infection within 4 weeks (defined as fever with a body temperature exceeding 38.5℃ or clear evidence of bacteremia or evidence of heart, brain, kidney, lung, etc.) Infectious changes in the liver and intestines), circulatory accidents within 6 months (malignant hypertension, myocardial infarction, severe/unstable angina pectoris, heart insufficiency above NYHA level 2, clinically significant supraventricular or Ventricular arrhythmia, cerebrovascular accident that has not recovered or caused serious sequelae), uncontrolled type 2 diabetes (fasting blood glucose\> 11.1mmol/L or glycosylated hemoglobin\> 8%), lung insufficiency (pulmonary function caused by any reason Decrease, defined as lung function test FEV1/FVC\<70%, FEV1\<80% predicted value).
• Past autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, autoimmune liver disease, autoimmune thyroiditis, systemic vasculitis, scleroderma, dermatomyositis, self Immune hemolytic anemia;
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500 IU/ml; hepatitis C, defined as HCV -RNA is higher than the detection limit of the analysis method) or combined with hepatitis B and C infection;
• The history of live attenuated vaccine vaccination within 28 days before the first study medication or the expected live attenuated vaccine vaccination during the study period;
• Imaging shows that the tumor invades large blood vessels or the investigator judges that the tumor is very likely to invade important blood vessels and cause fatal bleeding during the follow-up study or other diseases with serious bleeding risk (the bleeding caused by simple cervical tumor rupture is not included)
• Previously received anti-angiogenesis targeted drug therapy, or other treatments for VEGFR inhibitors;
• There is evidence of active tuberculosis infection within 1 year before screening;
• Any other malignant tumor has been diagnosed within 5 years before entering the study, except for fully treated basal cell carcinoma or squamous cell skin cancer or cervical carcinoma in situ;
• Major surgery has been performed within 28 days before randomization (tissue biopsy required for diagnosis and central venous catheter insertion via peripheral venipuncture \[PICC\] are allowed);
• Arteriovenous thrombosis events that occurred within 6 months before randomization, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis (venous thrombosis caused by intravenous catheterization due to pre-chemotherapy, which has been cured by the investigator Except) and pulmonary embolism;
• Subjects who have previously received or plan to receive allogeneic bone marrow transplantation or solid organ transplantation;
• There is intestinal obstruction with significant clinical significance, intestinal repair, intestinal anastomosis or intestinal fistula occurs at any time for any reason;
• Subjects with symptoms of hemoptysis and the maximum daily volume of hemoptysis ≥2.5 mL within 2 months before entering the study. Have had significant clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before entering the study, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline stool occult blood++ or above, or suffering from vasculitis, etc.; Known to have inherited or acquired bleeding and thrombotic tendency, such as: hemophilia, blood coagulation disorder, thrombocytopenia, hypersplenism, etc.;
• Macroscopic hematuria or urinary bleeding indicated by other evidence;
• Are receiving thrombolysis or need long-term anticoagulation therapy with warfarin or heparin, or need long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day)

Sponsors & Collaborators

• Zhongnan Hospital: lead

Study Sites (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

RECRUITING

Related Publications (5)

• Krill LS, Tewari KS. Integration of bevacizumab with chemotherapy doublets for advanced cervical cancer. Expert Opin Pharmacother. 2015 Apr;16(5):675-83. doi: 10.1517/14656566.2015.1010511. Epub 2015 Feb 3.

  PMID: 25643984 BACKGROUND

• Monk BJ, Sill MW, Burger RA, Gray HJ, Buekers TE, Roman LD. Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol. 2009 Mar 1;27(7):1069-74. doi: 10.1200/JCO.2008.18.9043. Epub 2009 Jan 12.

  PMID: 19139430 BACKGROUND

• Schefter T, Winter K, Kwon JS, Stuhr K, Balaraj K, Yaremko BP, Small W Jr, Sause W, Gaffney D; Radiation Therapy Oncology Group (RTOG). RTOG 0417: efficacy of bevacizumab in combination with definitive radiation therapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma. Int J Radiat Oncol Biol Phys. 2014 Jan 1;88(1):101-5. doi: 10.1016/j.ijrobp.2013.10.022.

  PMID: 24331655 BACKGROUND

• Youn SH, Kim YJ, Seo SS, Kang S, Lim MC, Chang HK, Park SY, Kim JY. Effect of addition of bevacizumab to chemoradiotherapy in newly diagnosed stage IVB cervical cancer: a single institution experience in Korea. Int J Gynecol Cancer. 2020 Jun;30(6):764-771. doi: 10.1136/ijgc-2020-001200. Epub 2020 Apr 9.

  PMID: 32276937 BACKGROUND

• 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.

  PMID: 29438373 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Cisplatin; Carboplatin; Brachytherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Radiotherapy; Therapeutics

Study Officials

• Hui Qiu, Ph. D.

  Wuhan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shaoxing Sun, M. D.

CONTACT

+8613871286154; sunshaoxing@whu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: No mask.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician and Director of Department of Radiation and Medical Oncology (Gynaecologic Oncology

Model Details: All participants will be included in one arm and receive chemoradiotherapy and anlotinib according to the protocol

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: February 25, 2021
• Study Start: March 12, 2021
• Primary Completion: October 1, 2025
• Study Completion: January 1, 2026
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)