Phase 1/2a/3 Evaluation of Adding AL3818 to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma (AL3818-US-002)

NCT ID: NCT02584478

Last Updated: 2023-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

294 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2024-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to standard platinum-based chemotherapy concurrently in Subjects with Recurrent or Metastatic Endometrial, Ovarian, Fallopian, Primary Peritoneal or Cervical Carcinoma.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This trial is a Phase 1b/2a/3 trial designed to evaluate the safety and efficacy of adding oral AL3818(Anlotinib, INN: Catequentinib) to standard platinum-based chemotherapy concurrently and continued as a maintenance therapy for up to 12 months, in subjects with recurrent or metastatic endometrial, ovarian, fallopian, primary peritoneal, or cervical carcinoma. AL3818 is a novel small molecule dual receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr) and vascular endothelial growth factor receptor (VEGFR). Preclinical studies of this agent in mouse models, including various cancer xenografts, have demonstrated that treatment of tumor-bearing mice with AL3818 induces tumor reductions.

Phase 1 \& 2: This study is divided into two parts. The objective of Part 1 is the evaluation of the safety and tolerability of adding oral AL3818 to standard carboplatin plus paclitaxel chemotherapy for a cycle of 21 days to determine the recommended Phase II dose (RP2D). Phase 1 / Part 1 is now complete. Part 2-The objective of Part 2 is evaluation of preliminary efficacy and the safety of adding oral AL3818 at the RP2D determined in Part 1 to carboplatin and paclitaxel chemotherapy for 6 cycles. Continuous maintenance mono therapy with 14 days on and 7 days off regimen at the RP2D will be conducted up to 12 months and is extendable beyond until disease progression. Phase I is closed and Phase 2 is closed.

Phase 3: This study is currently a Phase III, multi-center, randomized trial with active control designed to evaluate the efficacy and safety of AL3818 8 mg plus background treatment (Active Arm) vs background treatment alone (Control Arm), where three background treatments, weekly paclitaxel, pegylated liposomal doxorubicin (PLD), and topotecan are utilized. Oral AL3818 8 mg may be given concurrently with background treatment or alone if the background treatment must be discontinued due to its toxicity for up to 24 cycles of therapy, in subjects with recurrent or metastatic platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer. Phase 3 is open.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Endometrial Carcinoma Ovarian Carcinoma Fallopian Tube Carcinoma Primary Peritoneal Carcinoma Cervical Carcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Overall duration of the study will be approximately 42 months. Part 1 and 2 of this study are not randomized and have no concurrent controls. AL3818 and chemotherapy will be administered in an open-label fashion. Phase III/Part 3 is unblinded and randomized. Within each one of the three background chemotherapy groups, subjects will be randomized at a 1:1 ratio stratified by prior angiogenesis inhibitors mainly Avastin use status (Yes or No) and number of prior treatment (≤3 or \>3) to receive AL3818 plus background chemotherapy (Active Arm) or background chemotherapy alone (Control Arm).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Phase 3 -Active Treatment Arm

Phase 3: AL3818 8 mg once daily in combination with one background chemotherapy in 21-day cycles. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:

* Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
* Pegylated liposomal doxorubicin (PLD)
* Topotecan

Group Type EXPERIMENTAL

AL3818

Intervention Type DRUG

Taken daily from Day 8 to Day 21 (14 days),administered orally combination with one background chemotherapy in 21-day cycles.

Paclitaxel

Intervention Type DRUG

Weekly single agent Paclitaxel will be administered on Day 1, 8, and 15 of each 21-day cycle. Suggested dose: 80 mg/m\^2 intravenously or local standard.

Paclitaxel may also be administered once weekly with a 1-week break every 3 weeks in lieu of every week

Pegylated Liposomal Doxorubicin (PLD)

Intervention Type DRUG

Single agent Pegylated Liposomal Doxorubicin (PLD) administered every 4 weeks on the following cycle days corresponding with AL3818 cycles until maximum cumulative dose per local standard reached.

Suggested dose: 40 mg/m\^2 intravenously or local standard

Topotecan

Intervention Type DRUG

Daily Topotecan on Days 1-5 of each 21-day cycle Suggested dose: 1.25 mg/m2 intravenously or local standard OR Weekly Topotecan with a 1 week break every 3 weeks. Suggested dose: 4 mg/m2 intravenously or local standard

Topotecan

Intervention Type DRUG

Weekly Topotecan with a 1 week break every 3 weeks Suggested dose: 4 mg/m2 intravenously or local standard

Phase 3-Control Treatment Arm

Control Treatment Arm: Background chemotherapy treatment alone. Platinum resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer subjects will be enrolled into one of the following three background chemotherapy groups:

* Weekly paclitaxel (default choice; if the subject is ineligible for paclitaxel, the investigator will select from PLD or topotecan)
* Pegylated liposomal doxorubicin (PLD)
* Topotecan

Group Type OTHER

Paclitaxel

Intervention Type DRUG

Weekly single agent Paclitaxel will be administered on Day 1, 8, and 15 of each 21-day cycle. Suggested dose: 80 mg/m\^2 intravenously or local standard.

Paclitaxel may also be administered once weekly with a 1-week break every 3 weeks in lieu of every week

Pegylated Liposomal Doxorubicin (PLD)

Intervention Type DRUG

Single agent Pegylated Liposomal Doxorubicin (PLD) administered every 4 weeks on the following cycle days corresponding with AL3818 cycles until maximum cumulative dose per local standard reached.

Suggested dose: 40 mg/m\^2 intravenously or local standard

Topotecan

Intervention Type DRUG

Daily Topotecan on Days 1-5 of each 21-day cycle Suggested dose: 1.25 mg/m2 intravenously or local standard OR Weekly Topotecan with a 1 week break every 3 weeks. Suggested dose: 4 mg/m2 intravenously or local standard

Topotecan

Intervention Type DRUG

Weekly Topotecan with a 1 week break every 3 weeks Suggested dose: 4 mg/m2 intravenously or local standard

Phase 1b: AL3818 plus carboplatin and paclitaxel

Phase 1b: Sequential deescalating dosing evaluation to determine the recommended Phase II dose (RP2D). For 21-day treatment cycles, cohort 1 (3 subjects) will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at an initial dose of 12 mg/day.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

AUC 5/6 on Day 1 of each 21-Day cycles

Paclitaxel

Intervention Type DRUG

175mg/m2 IV over 3 hours on Day 1 of each 21-Day cycle

AL3818

Intervention Type DRUG

Taken daily from Day 8 to Day 21 (14 days). Administered orally.

Phase 2a: AL3818 plus carboplatin and paclitaxel

Phase 2a: subjects will receive chemotherapy and oral AL3818 for 6 cycles (18 weeks, 21-day cycles of treatment) followed by continuous maintenance treatment of oral AL3818 for up to 12 months. Subjects will be administered carboplatin (AUC 5/6 over 30 minutes) and paclitaxel (175mg/m2 over 3 hours) intravenously on Day 1. AL3818 is orally administered daily starting on Day 8 until Day 21 (14 days) at the RP2D found in Phase 1b.

Group Type EXPERIMENTAL

Carboplatin

Intervention Type DRUG

AUC 5/6 on Day 1 of each 21-Day cycles

Paclitaxel

Intervention Type DRUG

175mg/m2 IV over 3 hours on Day 1 of each 21-Day cycle

AL3818

Intervention Type DRUG

Taken daily from Day 8 to Day 21 (14 days). Administered orally.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

AL3818

Taken daily from Day 8 to Day 21 (14 days),administered orally combination with one background chemotherapy in 21-day cycles.

Intervention Type DRUG

Paclitaxel

Weekly single agent Paclitaxel will be administered on Day 1, 8, and 15 of each 21-day cycle. Suggested dose: 80 mg/m\^2 intravenously or local standard.

Paclitaxel may also be administered once weekly with a 1-week break every 3 weeks in lieu of every week

Intervention Type DRUG

Pegylated Liposomal Doxorubicin (PLD)

Single agent Pegylated Liposomal Doxorubicin (PLD) administered every 4 weeks on the following cycle days corresponding with AL3818 cycles until maximum cumulative dose per local standard reached.

Suggested dose: 40 mg/m\^2 intravenously or local standard

Intervention Type DRUG

Topotecan

Daily Topotecan on Days 1-5 of each 21-day cycle Suggested dose: 1.25 mg/m2 intravenously or local standard OR Weekly Topotecan with a 1 week break every 3 weeks. Suggested dose: 4 mg/m2 intravenously or local standard

Intervention Type DRUG

Topotecan

Weekly Topotecan with a 1 week break every 3 weeks Suggested dose: 4 mg/m2 intravenously or local standard

Intervention Type DRUG

Carboplatin

AUC 5/6 on Day 1 of each 21-Day cycles

Intervention Type DRUG

Paclitaxel

175mg/m2 IV over 3 hours on Day 1 of each 21-Day cycle

Intervention Type DRUG

AL3818

Taken daily from Day 8 to Day 21 (14 days). Administered orally.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Anlotinib Hydrochloride Anlotinib Catequentinib Daily Topotecan Weekly Topotecan Paraplatin Taxol

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Female ≥ 18 years of age
2. Histologically proven diagnosis of:

a. Endometrial and other uterine cancers with tumors of all histologies i. Recurrent Stage I to II endometrial and other uterine cancers, after at least one prior line of standard therapy, requiring further treatment with platinum-based chemotherapy ii. Advanced Stage III to IV endometrial and other uterine cancers requiring treatment with platinum-based chemotherapy

b. Ovarian Cancer: Platinum-sensitive or platinum-resistant recurrent or metastatic ovarian, fallopian, or primary peritoneal cancer treated with at least one prior line of platinum-based chemotherapy and requiring further treatment.(Part 1/Phase Ib, Part 2/Phase 2a)

Platinum-sensitive is defined as cancer progression ≥ 6 months after platinum- based chemotherapy. Platinum-resistant is defined as cancer progression \< 6 months after platinum-based chemotherapy.

Histologic cell types eligible are endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified.

Phase III/Part 3:

(1) Platinum-resistant (progression within 6 months after last platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer that meets one of the following criteria: i. Subject has received at least two prior lines of systemic therapy including a bevacizumab-containing regimen as standard of care ii. Subject has received at least two prior lines of systemic therapy, has not received a prior bevacizumab-containing regimen and is not eligible for a bevacizumab containing regimen based on Investigator's assessment (2) Platinum-refractory (progression during first-line platinum-based chemotherapy) ovarian, fallopian, or primary peritoneal cancer after at least one prior line of systemic therapy (3) For groups 1-2 above: Subjects with positive deleterious or suspected deleterious, germline or somatic BRCA mutated status must have received a PARP inhibitor as a prior line of therapy.

c. Cervical cancer: recurrent or metastatic cervical cancer that is not amenable to curative treatment with surgery and/or radiation therapy after at least one prior line of standard therapy, requiring further treatment. Histologic cell types eligible are squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma

3\. Have measureable disease defined by RECIST 1.1 confirmed by CT or MRI scan within 28 days of enrollment.

4\. Life expectancy of ≥ 3 months at the time of enrollment.

5\. Able to take orally administered study medication.

6\. Have adequate baseline function and performance status within 28 days of enrollment:

1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3
2. Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN) or if creatinine is \> 1.5 x ULN, creatinine clearance must be \> 50 mL/min.
3. Hepatic function: bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for subjects with Gilbert Syndrome; AST and ALT ≤ 3.0 × ULN.
4. Coagulation profile: international normalized ratio (INR) is ≤ 1.5 and an aPTT or PTT \< 1.2 x ULN
5. ECOG performance ≤ 2

7\. Women of child-bearing potential must agree to use contraceptive measures starting 1 week before C1D1 until 4 weeks after the last dose of study treatment and have a negative serum pregnancy test within 28 days of enrollment.

8\. Provide written informed consent and authorization permitting release of Protected Health Information.

9\. Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures.

Exclusion Criteria

1. Serious, non-healing wound, ulcer or bone fracture.
2. Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to C1D1 (a major surgical procedure is defined as requiring general anesthesia).
3. (Intentionally left blank)
4. Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
5. History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor; seizures not controlled with standard medical therapy; and history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months of enrollment.

a. Subjects with metastatic CNS tumors may participate in this study if the subject is \> 28 days from therapy completion (including radiation and/or surgery), is clinically stable at the time of study enrollment, and is not receiving corticosteroid therapy.
6. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a urine protein of 1+ on dipstick or ≥ 30 mg/dl at baseline should undergo a 24-hour urine collection and demonstrate \< 1000 mg protein per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be \<1.0 to allow participation in the study.
7. Clinically significant cardiovascular disease including uncontrolled hypertension; myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix E); serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease.
8. Women who are pregnant or nursing.
9. (Intentionally left blank)
10. Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
11. Hemoptysis within 3 months prior to enrollment.
12. Acute or chronic liver disease, active hepatitis A or B with known cirrhosis or liver dysfunction.
13. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment.
14. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or life-threatening medical condition that required it.
15. Known history of human immunodeficiency virus infection (HIV).
16. Active bacterial infections requiring systemic antibiotics (excluding uncomplicated urinary tract infection).
17. Other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years prior to enrollment or whose previous cancer treatment contraindicates this protocol therapy.
18. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months prior to enrollment that in the opinion of the investigator may place the subject at risk of side effects on an anti-angiogenesis product.
19. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection).
20. Intra-abdominal abscess within the last 3 months of enrollment.
21. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systolic BP \>160 mm Hg or diastolic BP \> 90 mm Hg pressure.
22. QTc \> 470 msec on screening ECG per Fridericia's formula.
23. History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
24. Concurrent use of concomitant medications that prolong the QT/QTc interval.
25. Baseline echocardiogram (within 56 days of enrollment) with left ventricular ejection fraction (LVEF) \< 50%.
26. History of difficulty swallowing, malabsorption, active partial or complete bowel obstruction, or other chronic gastrointestinal disease or condition that may hamper compliance and/or absorption of AL3818.
27. History of pancreatitis; history of renal disease that includes histologically confirmed glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal nephropathy or other renal insufficiencies.
28. Treatment with an investigational agent within 28 days of enrollment.
29. Known recreational substance abuse.
30. Anticoagulation therapy with warfarin. Subjects treated with heparin, low molecular weight heparin, or any other anticoagulant may be included provided the subject has been on a stable therapeutic dose of the anticoagulant for at least 14 days prior to enrollment.
31. Known hypersensitivity to AL3818 or components of the formulation.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Advenchen Laboratories, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Clinical Director

Role: STUDY_DIRECTOR

Advenchen Laboratories, LLC

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The Oncology Institute of Hope and Innovation

Long Beach, California, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Baptist Health Lexington Oncology Research

Lexington, Kentucky, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

AHN West Penn Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UTSW

Dallas, Texas, United States

Site Status

University of Wisconsin Madison

Madison, Wisconsin, United States

Site Status

Henan Cancer Hospital

Hefei, Henan, China

Site Status

Jilin Cancer Hospital

Changchun, Jilin, China

Site Status

The First Hospital of China Medical University

Shenyang, Shenyang, China

Site Status

Zhongda Hospital Southeast University

Chongqing, Sichuan, China

Site Status

Tianjin Central Hospital of Gynecology Obstetrics

Tianjin, Tianjin Municipality, China

Site Status

Obstetrics&Gynecology Hospital of Fudan University

Shanghai, Yangpu District, China

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Chongqing University Cancer Hospital

Chongqing, , China

Site Status

Weifang People's Hospital

Weifang, , China

Site Status

National Cancer Institute IRCCS "G. Pascale" Foundation

Naples, Campania, Italy

Site Status

University Hospital of Bologna-IRCCS

Bologna, Emilia-Romagna, Italy

Site Status

Romagnolo Institute For the Study of Tumors "Dino Amadori"

Meldola (FC), Forlì-Cesena, Italy

Site Status

Cannizzaro Emergency Hospital

Catania, , Italy

Site Status

Complex Structure Gynecology Oncology National Cancer Institute of Milan

Milan, , Italy

Site Status

Operative Unit of Oncology

Ravenna, , Italy

Site Status

Agostino Gemelli University Hospital Rome

Rome, , Italy

Site Status

Campus Bio Medico University Hospital Foundation

Rome, , Italy

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Korea University Guro Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital

Seoul, , South Korea

Site Status

Hospital Universitario Reina Sofía

Córdoba, Andalusia, Spain

Site Status

Hospital Regional Universitario de Málaga

Málaga, Andalusia, Spain

Site Status

ICO Badalona

Badalona, Catalonia, Spain

Site Status

Hospital Universitari Vall d'Hebrón

Barcelona, Catalonia, Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, Valencia, Spain

Site Status

Hospital Clínic de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

HCU Virgen Arrixaca

Murcia, , Spain

Site Status

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States China Italy South Korea Spain United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004 Dec;56(4):549-80. doi: 10.1124/pr.56.4.3.

Reference Type BACKGROUND
PMID: 15602010 (View on PubMed)

Kondo Y, Arii S, Mori A, Furutani M, Chiba T, Imamura M. Enhancement of angiogenesis, tumor growth, and metastasis by transfection of vascular endothelial growth factor into LoVo human colon cancer cell line. Clin Cancer Res. 2000 Feb;6(2):622-30.

Reference Type BACKGROUND
PMID: 10690548 (View on PubMed)

Roskoski R Jr. Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol. 2007 Jun;62(3):179-213. doi: 10.1016/j.critrevonc.2007.01.006. Epub 2007 Feb 26.

Reference Type BACKGROUND
PMID: 17324579 (View on PubMed)

Dickson C, Spencer-Dene B, Dillon C, Fantl V. Tyrosine kinase signalling in breast cancer: fibroblast growth factors and their receptors. Breast Cancer Res. 2000;2(3):191-6. doi: 10.1186/bcr53. Epub 2000 Mar 25.

Reference Type BACKGROUND
PMID: 11250709 (View on PubMed)

Cole C, Lau S, Backen A, Clamp A, Rushton G, Dive C, Hodgkinson C, McVey R, Kitchener H, Jayson GC. Inhibition of FGFR2 and FGFR1 increases cisplatin sensitivity in ovarian cancer. Cancer Biol Ther. 2010 Sep 1;10(5):495-504. doi: 10.4161/cbt.10.5.12585. Epub 2010 Sep 4.

Reference Type BACKGROUND
PMID: 20595807 (View on PubMed)

Raja FA, Griffin CL, Qian W, Hirte H, Parmar MK, Swart AM, Ledermann JA. Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer. Br J Cancer. 2011 Sep 27;105(7):884-9. doi: 10.1038/bjc.2011.334. Epub 2011 Aug 30.

Reference Type BACKGROUND
PMID: 21878941 (View on PubMed)

Ledermann JA, Perren TJ, Raja FA, et al: Randomized double-blind phase III trial of cediranib (AZD 2171) in relapsed platinum-sensitive ovarian cancer: Results of the ICON6 trial. European Cancer Congress. Abstract 10. Presented September 30, 2013.

Reference Type BACKGROUND

Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets. 2010 Aug;11(8):1000-17. doi: 10.2174/138945010791591395.

Reference Type BACKGROUND
PMID: 20426765 (View on PubMed)

Shen GH, Ghazizadeh M, Kawanami O, Shimizu H, Jin E, Araki T, Sugisaki Y. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma. Br J Cancer. 2000 Jul;83(2):196-203. doi: 10.1054/bjoc.2000.1228.

Reference Type BACKGROUND
PMID: 10901370 (View on PubMed)

Chen CA, Cheng WF, Lee CN, Chen TM, Kung CC, Hsieh FJ, Hsieh CY. Serum vascular endothelial growth factor in epithelial ovarian neoplasms: correlation with patient survival. Gynecol Oncol. 1999 Aug;74(2):235-40. doi: 10.1006/gyno.1999.5418.

Reference Type BACKGROUND
PMID: 10419737 (View on PubMed)

Yoneda J, Kuniyasu H, Crispens MA, Price JE, Bucana CD, Fidler IJ. Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst. 1998 Mar 18;90(6):447-54. doi: 10.1093/jnci/90.6.447.

Reference Type BACKGROUND
PMID: 9521169 (View on PubMed)

Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, Douglas J, Burger RA, Armstrong D, Wenham R, McGuire W. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol. 2007 Nov 20;25(33):5180-6. doi: 10.1200/JCO.2007.12.0782.

Reference Type BACKGROUND
PMID: 18024865 (View on PubMed)

Burger RA, Brady MF, Bookman MA et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC) or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. Journal of Clinical Oncology, 2010 ASCO Annual Meeting Proceedings. Vol. 28, No 18S, 2010 June 20 suppl: Abstract LBA1

Reference Type BACKGROUND

Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. doi: 10.1200/JCO.2012.42.0505. Epub 2012 Apr 23.

Reference Type BACKGROUND
PMID: 22529265 (View on PubMed)

Yokoyama Y, Charnock-Jones DS, Licence D, Yanaihara A, Hastings JM, Holland CM, Emoto M, Sakamoto A, Sakamoto T, Maruyama H, Sato S, Mizunuma H, Smith SK. Expression of vascular endothelial growth factor (VEGF)-D and its receptor, VEGF receptor 3, as a prognostic factor in endometrial carcinoma. Clin Cancer Res. 2003 Apr;9(4):1361-9.

Reference Type BACKGROUND
PMID: 12684405 (View on PubMed)

Holland CM, Day K, Evans A, Smith SK. Expression of the VEGF and angiopoietin genes in endometrial atypical hyperplasia and endometrial cancer. Br J Cancer. 2003 Sep 1;89(5):891-8. doi: 10.1038/sj.bjc.6601194.

Reference Type BACKGROUND
PMID: 12942123 (View on PubMed)

Giatromanolaki A, Sivridis E, Brekken R, Thorpe PE, Anastasiadis P, Gatter KC, Harris AL, Koukourakis MI; Tumour and Angiogenesis Research Group. The angiogenic "vascular endothelial growth factor/flk-1(KDR) receptor" pathway in patients with endometrial carcinoma: prognostic and therapeutic implications. Cancer. 2001 Nov 15;92(10):2569-77. doi: 10.1002/1097-0142(20011115)92:103.0.co;2-3.

Reference Type BACKGROUND
PMID: 11745191 (View on PubMed)

Gornall RJ, Anthony FW, Coombes EJ, Hogston P, Woolas RP. Investigation of women with endometrial carcinoma using serum vascular endothelial growth factor (VEGF) measurement. Int J Gynecol Cancer. 2001 Mar-Apr;11(2):164-6. doi: 10.1046/j.1525-1438.2001.011002164.x.

Reference Type BACKGROUND
PMID: 11328416 (View on PubMed)

McMeekin DS, Sill MW, Benbrook D, Darcy KM, Stearns-Kurosawa DJ, Eaton L, Yamada SD; Gynecologic Oncology Group. A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: a Gynecologic Oncology Group study. Gynecol Oncol. 2007 May;105(2):508-16. doi: 10.1016/j.ygyno.2007.01.019. Epub 2007 Feb 15.

Reference Type BACKGROUND
PMID: 17306350 (View on PubMed)

Talvensaari-Mattila A, Soini Y, Santala M. VEGF and its receptors (flt-1 and KDR/flk-1) as prognostic indicators in endometrial carcinoma. Tumour Biol. 2005 Mar-Apr;26(2):81-7. doi: 10.1159/000085589. Epub 2005 May 3.

Reference Type BACKGROUND
PMID: 15867479 (View on PubMed)

Saito M, Sato Y, Watanabe J, Kuramoto H, Kaba S, Fukuda T. Angiogenic factors in normal endometrium and endometrial adenocarcinoma. Pathol Int. 2007 Mar;57(3):140-7. doi: 10.1111/j.1440-1827.2006.02071.x.

Reference Type BACKGROUND
PMID: 17295646 (View on PubMed)

Hirai M, Nakagawara A, Oosaki T, Hayashi Y, Hirono M, Yoshihara T. Expression of vascular endothelial growth factors (VEGF-A/VEGF-1 and VEGF-C/VEGF-2) in postmenopausal uterine endometrial carcinoma. Gynecol Oncol. 2001 Feb;80(2):181-8. doi: 10.1006/gyno.2000.6056.

Reference Type BACKGROUND
PMID: 11161857 (View on PubMed)

Giatromanolaki A, Koukourakis MI, Turley H, Sivridis E, Harris AL, Gatter KC; Tumour and Angiogenesis Research Group. Phosphorylated KDR expression in endometrial cancer cells relates to HIF1alpha/VEGF pathway and unfavourable prognosis. Mod Pathol. 2006 May;19(5):701-7. doi: 10.1038/modpathol.3800579.

Reference Type BACKGROUND
PMID: 16557278 (View on PubMed)

Aghajanian C, Sill MW, Darcy KM, Greer B, McMeekin DS, Rose PG, Rotmensch J, Barnes MN, Hanjani P, Leslie KK. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65. doi: 10.1200/JCO.2010.32.6397. Epub 2011 May 2.

Reference Type BACKGROUND
PMID: 21537039 (View on PubMed)

Guidi AJ, Abu-Jawdeh G, Berse B, Jackman RW, Tognazzi K, Dvorak HF, Brown LF. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia. J Natl Cancer Inst. 1995 Aug 16;87(16):1237-45. doi: 10.1093/jnci/87.16.1237.

Reference Type BACKGROUND
PMID: 7563170 (View on PubMed)

Wiggins DL, Granai CO, Steinhoff MM, Calabresi P. Tumor angiogenesis as a prognostic factor in cervical carcinoma. Gynecol Oncol. 1995 Mar;56(3):353-6. doi: 10.1006/gyno.1995.1062.

Reference Type BACKGROUND
PMID: 7535719 (View on PubMed)

Ravazoula P, Zolota V, Hatjicondi O, Sakellaropoulos G, Kourounis G, Maragoudakis ME. Assessment of angiogenesis in human cervical lesions. Anticancer Res. 1996 Nov-Dec;16(6B):3861-4.

Reference Type BACKGROUND
PMID: 9042271 (View on PubMed)

Dellas A, Moch H, Schultheiss E, Feichter G, Almendral AC, Gudat F, Torhorst J. Angiogenesis in cervical neoplasia: microvessel quantitation in precancerous lesions and invasive carcinomas with clinicopathological correlations. Gynecol Oncol. 1997 Oct;67(1):27-33. doi: 10.1006/gyno.1997.4835.

Reference Type BACKGROUND
PMID: 9345352 (View on PubMed)

Cella DF. Manual for the Functional Assessment of Cancer Therapy (FACT) Measurement System (version 4). Center for Outcomes, Research and Education (CORE), Northwestern University, Chicago, 1997

Reference Type BACKGROUND

Wright JD, Viviano D, Powell MA, Gibb RK, Mutch DG, Grigsby PW, Rader JS. Bevacizumab combination therapy in heavily pretreated, recurrent cervical cancer. Gynecol Oncol. 2006 Nov;103(2):489-93. doi: 10.1016/j.ygyno.2006.03.023. Epub 2006 May 2.

Reference Type BACKGROUND
PMID: 16647106 (View on PubMed)

36. Krishnansu Sujata Tewari, Michael Sill, Harry J. Long,et al. Plenary Session, Abstract # 3, J Clin Oncol 31, 2013 (suppl; abstract 3)

Reference Type BACKGROUND

Pectasides D, Xiros N, Papaxoinis G, Pectasides E, Sykiotis C, Koumarianou A, Psyrri A, Gaglia A, Kassanos D, Gouveris P, Panayiotidis J, Fountzilas G, Economopoulos T. Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol. 2008 May;109(2):250-4. doi: 10.1016/j.ygyno.2008.01.028. Epub 2008 Mar 4.

Reference Type BACKGROUND
PMID: 18299146 (View on PubMed)

Tinker AV, Bhagat K, Swenerton KD, Hoskins PJ. Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Gynecol Oncol. 2005 Jul;98(1):54-8. doi: 10.1016/j.ygyno.2005.03.037.

Reference Type BACKGROUND
PMID: 15904950 (View on PubMed)

Parmar MK, Ledermann JA, Colombo N, du Bois A, Delaloye JF, Kristensen GB, Wheeler S, Swart AM, Qian W, Torri V, Floriani I, Jayson G, Lamont A, Trope C; ICON and AGO Collaborators. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet. 2003 Jun 21;361(9375):2099-106. doi: 10.1016/s0140-6736(03)13718-x.

Reference Type BACKGROUND
PMID: 12826431 (View on PubMed)

Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

Reference Type DERIVED
PMID: 37185961 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

AL3818-US-002

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.