Tumor Response Time of Palbociclib in Combination With AI in Real-world Chinese Patients

Breast Neoplasms Clinical Trial

Official title:

An Open-label, Prospective Study of Tumor Response Time of Palbociclib in Combination With AI in Real-world First-line Treatment of Postmenopausal Chinese Patients With ER (+) HER2 (-) Metastatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04858997
• Other study ID #: PAL-ZJCC-02
• Status: Recruiting
• Phase: Phase 2
• Start date: April 22, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: April 2021
• Source: Zhejiang Cancer Hospital
• Contact: Wen-Ming Cao, Ph.D., M.D.
• Phone: 8613858064001
• Email: caowm[@]zjcc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The international treatment guidelines now include recommendations for the use of CDK 4/6 inhibitors in combination with hormone agents for the treatment of postmenopausal women with hormone-receptor-positive/HER2-negative ABC as the first-line standard therapy in endocrine sensitive patients. Nevertheless, it is generally thought that chemotherapy is associated with greater and earlier tumor response, especially in case of high burden of disease. In a retrospective analysis of real-world clinical practice (2002-2012) from US, only 60% of patients initiated ET as the first treatment following metastatic diagnosis . In the real-life world of China, a large number of HR+/HER2- ABC patients with non-visceral crisis also received chemotherapy in first-line treatment, even though the ORR is similar compared with CDK4/6 inhibitors with endocrine therapy. Zhejiang Cancer Hospital retrospective analysis of 5 cases of advanced breast cancer first-line use of Ibance + ET, they were evaluated within 50 days (from 27days to 50days). Based on the early response time observed in real-world data mentioned above, it is proposed a prospective study to further observe the tumor reduction rate in real-world, including to identify the time of patient symptom improvement according to the quality of life scale.

Description:

According to the early assessment(4 weeks) , this prospective study comprehensively investigate TTR of Palbociclib+ET in the first line treatment for HR+/HER2- MBC patients in China real-world study. Furthermore, evaluate the Early Tumor Shrinkage(ETS) of Palbociclib + ET, and assess Treatment Free Interval (TFI) with TTR and ETS；TFI was analyzed at the following time points: ≤24, >24, ≤36, > 36, ≤48, >48 months. Accroding to the follow-up of QoL questionnaire, understand the clinical symptoms improvements time. Meanwhile, cooperation with radiology department, establish a model for predicting early response by observing the imaging and clinical pathological characteristics of patients with ETS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult women (= 18 years of age) with proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.

2. Documentation of histologically or cytologically confirmed diagnosis of estrogen-receptor positive (ER+, > 10%) breast cancer based on local laboratory results.

3. Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease.

4. Postmenopausal women.

5. At least one measurable lesion as defined per RECIST v.1.1.

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.

7. Adequate organ and marrow function.

8. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Patients with advanced, symptomatic, visceral spread, that are at risk of

life-threatening complications including any of the following:

• massive uncontrolled effusions [pleural, pericardial, peritoneal]
• pulmonary lymphangitis,
• over 50% liver involvement

2. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis,or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.

3. Prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.

4. Prior treatment with any CDK4/6 inhibitor.

5. QTc >480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).

6. Female patients who are pregnant or nursing.

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Palbociclib
Palbociclib,125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
• AI
AI, orally once daily (continuously)

Locations

Country	Name	City	State
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital	Pfizer

Country where clinical trial is conducted

China, 

References & Publications (9)

Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, André F, Harbeck N, Aguilar Lopez B, Barrios CH, Bergh J, Biganzoli L, Boers-Doets CB, Cardoso MJ, Carey LA, Cortés J, Curigliano G, Diéras V, El Saghir NS, Eniu A, Fallowfield L, Francis PA, Gelmon K — View Citation

Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. — View Citation

Grünwald V, Lin X, Kalanovic D, Simantov R. Early Tumour Shrinkage: A Tool for the Detection of Early Clinical Activity in Metastatic Renal Cell Carcinoma. Eur Urol. 2016 Dec;70(6):1006-1015. doi: 10.1016/j.eururo.2016.05.010. Epub 2016 May 26. — View Citation

Janni W, Alba E, Bachelot T, Diab S, Gil-Gil M, Beck TJ, Ryvo L, Lopez R, Tsai M, Esteva FJ, Auñón PZ, Kral Z, Ward P, Richards P, Pluard TJ, Sutradhar S, Miller M, Campone M. First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2- a — View Citation

Lobbezoo DJ, van Kampen RJ, Voogd AC, Dercksen MW, van den Berkmortel F, Smilde TJ, van de Wouw AJ, Peters FP, van Riel JM, Peters NA, de Boer M, Borm GF, Tjan-Heijnen VC. Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2-positive — View Citation

Piessevaux H, Buyse M, Schlichting M, Van Cutsem E, Bokemeyer C, Heeger S, Tejpar S. Use of early tumor shrinkage to predict long-term outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol. 2013 Oct 20;31(30):3764-75. doi: 10.1200/J — View Citation

Swallow E, Zhang J, Thomason D, Tan RD, Kageleiry A, Signorovitch J. Real-world patterns of endocrine therapy for metastatic hormone-receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) breast cancer patients in the United Sta — View Citation

Turner NC, Finn RS, Martin M, Im SA, DeMichele A, Ettl J, Diéras V, Moulder S, Lipatov O, Colleoni M, Cristofanilli M, Lu DR, Mori A, Giorgetti C, Iyer S, Bartlett CH, Gelmon KA. Clinical considerations of the role of palbociclib in the management of adva — View Citation

Wei M, Ye Q, Wang X, Wang M, Hu Y, Yang Y, Yang J, Cai J. Early tumor shrinkage served as a prognostic factor for patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy. Medicine (Baltimore). 2018 May;97(19):e0632. do — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Early Tumor Shrinkage (ETS)	10% change in the sum of the longest diameters (SLD) of target lesions at the first scan after 4weeks and 8weeks of treatment.	4 weeks, 8weeks
Primary	Time To Response (TTR)	Time to first documented complete of partial response.	Up to approximately 24 months
Secondary	Objective Response Rate (ORR)	ORR is defined as the overall complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1)	Up to approximately 24 months
Secondary	Number of participants with Adverse Events per CTCAE version 4.03 and type	Safety will be determined by type, severity of adverse events per CTCAE version 4.03 and type	Up to approximately 24 months
Secondary	Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30	At least 10% relative to baseline worsening of the corresponding scale score (without further improvement above the threshold) or death due to any cause.	Up to approximately 24 months
Secondary	Overall Survival (OS)	time to death due to any cause	Randomization to death from any cause, through the end of study (approximately 60months)]