Multicenter Phase II Study of Apatinib in Patients With Advanced Breast Cancer(CABC006)

• Sponsor: Peking University Cancer Hospital & Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02878057
• Collaborator: Hebei Medical University Fourth Hospital (Other), Peking University First Hospital (Other), Peking University Third Hospital (Other), Shanxi Province Cancer Hospital (Other)
• Enrollment: 30
• Arm: 1
• Actual Duration (Months): 52.1

Study Details

Study Description

Brief Summary

The treatment of the patients with recurrent and metastatic breast cancer remains a major problem. There is still a lack of effective targeted therapy for Her-2 negative breast cancer.Based on the present researches on the anti-angiogenesis drugs in advanced breast cancer, the investigators believe that it is necessary to further explore the efficacy and safety of apatinib in advanced breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Apatinib	Phase 2

Detailed Description

With the comprehensive treatment of breast cancer wildly used in the clinical practice, the life quality of the patients with breast cancer has been improved greatly, and the survival of the patients has been extended as well. However, the treatment of the patients with recurrent and metastatic breast cancer remains a major problem. There is still a lack of effective targeted therapy for Her-2 negative breast cancer.

Based on the present researches on the anti-angiogenesis drugs in advanced breast cancer, the investigators believe that it is necessary to further explore the efficacy and safety of apatinib in advanced breast cancer. The aim of this research is to evaluate the progression-free survival (PFS) of the patients with HER-2 negative advanced breast cancer with chest wall metastasis in the treatment of apatinib.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter Phase II Study of Apatinib in Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis
• Actual Study Start Date: May 1, 2016
• Actual Primary Completion Date: Sep 2, 2020
• Actual Study Completion Date: Sep 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Advanced Breast Cancer Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)	Drug: Apatinib; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive); Other Names: Apatinib Mesylate Tablets

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [evaluation per 2 cycles (8 weeks), up to 6 months;From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

2. Overall Survival [evaluation per 2 cycles (8 weeks), up to 55 months]

   survival from first dose to death or last follow up

Secondary Outcome Measures

1. Objective Response Rate [evaluation per 2 cycles (8 weeks), up to 55 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective response rate = CR + PR.

2. Disease Control Rate [evaluation per 2 cycles (8 weeks), up to 55 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression Disease (PD), >=20% increase in the sum of the longest diameter of target lesions or appearance of new lesions; Stable Disease (SD), between PR and PD. Disease control rate (DCR) = CR + PR + SD.

3. Number of Participants With Adverse Events [evaluation per 2 cycles (8 weeks), up to 55 months]

   all kind of adverse events, including hypertension, proteinuria, nausea, fatigue, and bilirubin increase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. HER-2 negative advanced breast cancer with chest wall metastasis confirmed by histology or cytological examination (patients who have received anthracyclines and/or paclitaxel in adjuvant chemotherapy).

2. Patients with recurrence or metastasis who have received no more than two lines of chemotherapy.

3. If hormone receptor is positive, endocrine therapy must have been performed for the patients with recurrence or metastasis, or the recurrence or metastasis occurred in less than two years of endocrine therapy.

4. ≥ 18 years old.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

6. A life expectancy of more than 3 months.

7. At least one measurable site of disease confirmed by CT or MRI according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was required.

8. If the target lesions are lymph nodes, the short diameter is required to be less than 1.5cm and the target lesions are not suitable for surgical treatment; target lesions have not been in radiotherapy or recurred in the radiation field.

9. Baseline blood routine examination in accordance with the following criteria: neutrophil counts more than 1.5109/L; platelet counts greater than 100109/L; hemoglobin greater than 9 g/dL (blood transfusion is allowed to achieve or maintain the index)

10. Liver function in accordance with the following criteria: total bilirubin less than 1.5 times the upper limit of normal value; aspartate aminotransferase (AST), alanine aminotransferase (ALT) less than 2.5 times the upper limit of normal value, less than 5 times the upper limit of normal value in patients with liver metastases.

11. Renal function in accordance with the following criteria: serum creatinine less than 1.25 times the upper limit of normal value, or the creatinine clearance rate calculated greater than 50 mL/min;

12. Women with fertility are willing to take contraceptive measures in the trial: when seven days before the drug delivery of serum or urine pregnancy test negative.

Exclusion Criteria:

1. receiving radiation therapy 28 days before enrolled. Radiotherapy before enrollment to relieve the metastatic bone pain is allowed, but medullary bone radiated should not exceed 30% of the total amount;

2. symptomatic central nervous system metastases;

3. current or recent (30 days before enrollment) use of another study drug or being involved in another clinical study;

4. Other malignant tumors that have occurred within 5 years (except for the cured or well-controlled cervical carcinoma in situ, skin squamous cell carcinoma, or skin basal cell carcinoma);

5. With hypertension and the blood pressure cannot be reduced to the normal range through antihypertensive drug treatment (systolic blood pressure greater than or equal to 140 mmHg or diastolic blood pressure greater than or equal to 90 mmHg).

6. With grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including QTc interval more than or equal to 450 ms for men, more than or equal to 470 ms for female);

7. according to the criteria of NYHA, cardiac insufficiency of grade III and IV or left ventricular ejection fraction (LVEF) less than 50% revealed by echocardiography;

8. abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN+4 seconds or APTT >1.5 times the ULN), with bleeding tendency or under thrombolysis or anticoagulation therapy;

9. within 3 months before enrollment, clinically significant bleeding symptoms occur, or having obvious bleeding tendency, such as gastrointestinal bleeding, bleeding gastric ulcer, occult blood + + and above in baseline period, or suffering from vasculitis, et al;

10. within 4 months before enrollment receiving major surgery or getting severe traumatic injury, fracture or ulcer;

11. having factors that affect the absorption of the oral drugs obviously, such as the inability to swallow, chronic diarrhea and intestinal obstruction, et al;

12. urine routine test with urinary protein more than ++, or 24 hour urinary protein more than 1.0 g;

13. with symptomatic serous cavity effusion, which needs to be surgically managed (including pleural effusion, ascites, pericardial effusion);

14. with other possible conditions that can affect the clinical research or evaluation of the results judged by the researchers.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Peking University Cancer Hospital & Institute
• Hebei Medical University Fourth Hospital
• Peking University First Hospital
• Peking University Third Hospital
• Shanxi Province Cancer Hospital

Investigators

• Study Chair: Huiping Li, MD, Peking University Cancer Hospital & Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 1, 2020

More Information

Publications

• D'Agostino RB Sr. Changing end points in breast-cancer drug approval--the Avastin story. N Engl J Med. 2011 Jul 14;365(2):e2. doi: 10.1056/NEJMp1106984. Epub 2011 Jun 27.
• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.
• Miles DW, Chan A, Dirix LY, Cortés J, Pivot X, Tomczak P, Delozier T, Sohn JH, Provencher L, Puglisi F, Harbeck N, Steger GG, Schneeweiss A, Wardley AM, Chlistalla A, Romieu G. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010 Jul 10;28(20):3239-47. doi: 10.1200/JCO.2008.21.6457. Epub 2010 May 24.
• Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76.
• Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. doi: 10.1200/JCO.2010.28.0982. Epub 2011 Mar 7.
• Valachis A, Polyzos NP, Patsopoulos NA, Georgoulias V, Mavroudis D, Mauri D. Bevacizumab in metastatic breast cancer: a meta-analysis of randomized controlled trials. Breast Cancer Res Treat. 2010 Jul;122(1):1-7. doi: 10.1007/s10549-009-0727-0. Epub 2010 Jan 9. Review.
• Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med. 1991 Jan 3;324(1):1-8.

• Responsible Party: Li Huiping, Head of the department of breast oncology, Peking University Cancer Hospital & Institute
• ClinicalTrials.gov Identifier: NCT02878057
• Other Study ID Numbers: 2016YJZ19
• First Posted: Aug 25, 2016
• Last Update Posted: Jan 27, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Li Huiping, Head of the department of breast oncology, Peking University Cancer Hospital & Institute: Apatinib; HER-2 Negative; Chest wall Metastasis; Multicenter Phase II Study; Breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Apatinib

Study Results

Participant Flow

Recruitment Details	finished recritment

Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive) Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
Period Title: Overall Study
STARTED	30
COMPLETED	26
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
Overall Participants	30
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49.5
Sex: Female, Male (Count of Participants)
Female	30 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	30 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Lines of Chemotherapy Prior to Enrollment (Count of Participants)
1	4 13.3%
2	10 33.3%
≥3	16 53.3%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	evaluation per 2 cycles (8 weeks), up to 6 months;From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive) Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
Measure Participants	26
Median (95% Confidence Interval) [months]	4.9

2. Primary Outcome

Title	Overall Survival
Description	survival from first dose to death or last follow up
Time Frame	evaluation per 2 cycles (8 weeks), up to 55 months

Outcome Measure Data

Analysis Population Description

Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis;

Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive) Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
Measure Participants	26
Median (Full Range) [months]	18

3. Secondary Outcome

Title	Objective Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective response rate = CR + PR.
Time Frame	evaluation per 2 cycles (8 weeks), up to 55 months

Outcome Measure Data

Analysis Population Description

Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis;

Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive) Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
Measure Participants	26
Count of Participants [Participants]	11 36.7%

4. Secondary Outcome

Title	Disease Control Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression Disease (PD), >=20% increase in the sum of the longest diameter of target lesions or appearance of new lesions; Stable Disease (SD), between PR and PD. Disease control rate (DCR) = CR + PR + SD.
Time Frame	evaluation per 2 cycles (8 weeks), up to 55 months

Outcome Measure Data

Analysis Population Description

Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis;

Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive) Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
Measure Participants	26
Count of Participants [Participants]	20 66.7%

5. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	all kind of adverse events, including hypertension, proteinuria, nausea, fatigue, and bilirubin increase.
Time Frame	evaluation per 2 cycles (8 weeks), up to 55 months

Outcome Measure Data

Analysis Population Description

Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis

Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive) Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
Measure Participants	30
Count of Participants [Participants]	15 50%

Adverse Events

Time Frame	through study completion, an median of 18 months
Adverse Event Reporting Description	The apatinib dose given was reduced from 500mg to 250mg for 60% of patients because of side effects.
Arm/Group Title	Advanced Breast Cancer
Arm/Group Description	Patients With HER-2 Negative Advanced Breast Cancer With Chest Wall Metastasis; Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive) Apatinib: Dosing regimen: apatinib tablets: 500 mg, Po, QD; 4 weeks as a cycle, continuous treatment until disease progression, death or intolerable toxicity (giving endocrine therapy simultaneously if hormone receptor positive)
All Cause Mortality
	Advanced Breast Cancer
	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)
Serious Adverse Events
	Advanced Breast Cancer
	Affected / at Risk (%)	# Events
Total	12/30 (40%)
Cardiac disorders
Hypertension	2/30 (6.7%)
General disorders
Fatigue	1/30 (3.3%)
Hepatobiliary disorders
Bilirubin increased	2/30 (6.7%)
Transaminase increased	1/30 (3.3%)
Renal and urinary disorders
proteinuria	6/30 (20%)
Other (Not Including Serious) Adverse Events
	Advanced Breast Cancer
	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)
General disorders
Infection	1/30 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.