Safety Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in Indian Participants With Breast Cancer

NCT02445586 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: ML29282
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 9

Brief Summary

This is a Phase 4, single-arm, open-label, multicenter study to assess the safety and efficacy of pertuzumab in combination with trastuzumab and docetaxel for the treatment of participants with human epidermal growth factor receptor 2 (HER2)-positive advanced (locally recurrent, unresectable, or metastatic) breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (27)

• Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant

  The number of participants with serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (\>) 1, or 0 serious adverse events. Participants with multiple occurrences of events (the ≥1 and \>1 serious adverse event categories) were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)

  The number of participants with serious adverse events was counted by the initial and most extreme levels of severity of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of serious adverse events of the same severity were only counted once per severity category.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Serious Adverse Events Related to Docetaxel

  The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Serious Adverse Events Related to Pertuzumab

  The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Serious Adverse Events Related to Trastuzumab

  The number of participants with serious adverse events was counted for any serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug

  The number of participants with serious adverse events was counted by the type of action taken with the study drug (docetaxel, pertuzumab, and trastuzumab) in response to the adverse event in the three following categories: infusion reduced, temporarily interrupted, or permanently discontinued. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events that required the same action to be taken with the study drug were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Serious Adverse Events by Event Outcome

  The number of participants with serious adverse events was counted by the event outcome in the six following categories: fatal, recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not resolved, or unknown. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events with the same outcome were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Hematological Abnormalities Reported as Serious Adverse Events

  The number of participants with hematological laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Serum Chemistry Abnormalities Reported as Serious Adverse Events

  The number of participants with serum chemistry laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Coagulation Abnormalities Reported as Serious Adverse Events

  The number of participants with coagulation laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death

  The number of participants who died due to a serious adverse event was counted by the cause of death.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant

  The number of participants with non-serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (\>) 1, or 0 non-serious adverse events. Participants with multiple occurrences of events (the ≥1 and \>1 non-serious adverse event categories) were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03

  The number of participants with non-serious adverse events was counted by the severity level of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of non-serious adverse events of the same severity were only counted once per severity category.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Non-Serious Adverse Events Related to Docetaxel

  The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with docetaxel, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Non-Serious Adverse Events Related to Pertuzumab

  The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with pertuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Non-Serious Adverse Events Related to Trastuzumab

  The number of participants with non-serious adverse events was counted for any non-serious adverse event that was related to study treatment with trastuzumab, in the investigator's judgment. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab

  The number of participants with non-serious adverse events was counted by the type of action taken with docetaxel and/or trastuzumab in response to the adverse event in the three following categories: no adjustment, dosage modified/interrupted, and discontinued. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab

  The number of participants with non-serious adverse events was counted by the type of action taken with pertuzumab in response to the adverse event in the three following categories: no action taken, infusion slow down, infusion interrupted, and appropriate medical therapies administered. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Non-Serious Adverse Events by Event Outcome

  The number of participants with non-serious adverse events was counted by the event outcome in the four following categories: resolved with no sequelae, resolved with sequelae, unresolved, or death. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events with the same outcome were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE)

  The number of participants with non-serious adverse events was counted according to whether the event was considered a treatment emergent adverse event (TEAE), which is defined as an adverse event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. Participants with multiple occurrences of non-serious adverse events were only counted once per category.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events

  The number of participants with hematological laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events

  The number of participants with serum chemistry laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events

  The number of participants with coagulation laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term.

  From Baseline until end of study (up to approximately 3 years)

• Number of Participants With Congestive Heart Failure

  From Baseline until end of study (up to approximately 3 years)

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time

  Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF of ≥50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution.

  Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)

• Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time

  Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF greater than or equal to (≥)50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. The following are definitions for the three categories of LVEF findings: 'Normal' was defined as LVEF ≥45%; 'Abnormal but not clinically significant' was defined as LVEF \<45% but not clinically significant in the investigator's judgment; 'Abnormal and clinically significant' was defined as LVEF \<45% and clinically significant in the investigator's judgment.

  Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)

• Number of Participants With Adverse Events Leading to Treatment Discontinuation

  The number of participants with any adverse event (serious or non-serious) that led to treatment discontinuation during the study was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one adverse event that led to treatment discontinuation may have been reported per participant.

  From Baseline until end of study (up to approximately 3 years)

Secondary Outcomes (8)

• Overall Response Rate

  From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

• Number of Participants by Best Overall Response

  From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

• Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis

  From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

• Median Duration of Progression-Free Survival

  From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)

• Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months

  Months 2, 3, 5, 6, 7, 8, 9, 11, 13, 15, 16, 17, 18, 19, 23, 24, 25, 27, 29, and 32

Study Arms (1)

Pertuzumab in Combination with Trastuzumab and Docetaxel

EXPERIMENTAL

Participants will receive pertuzumab in combination with trastuzumab and docetaxel every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Drug: Docetaxel; Drug: Pertuzumab; Drug: Trastuzumab

Interventions

Docetaxel DRUG

Participants will receive docetaxel in line with locally approved Prescribing Information. After Cycle 6 (cycle length = 21 days), continuation of docetaxel treatment will be at the discretion of the investigator. Docetaxel will be administered after pertuzumab and trastuzumab.

Pertuzumab in Combination with Trastuzumab and Docetaxel

Pertuzumab DRUG

Participants will receive pertuzumab at an initial dose of 840 milligrams (mg) as a 60-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 420 mg as a 30 to 60-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Also known as: Perjeta®

Pertuzumab in Combination with Trastuzumab and Docetaxel

Trastuzumab DRUG

Participants will receive trastuzumab at an initial dose of 8 milligrams per kilogram (mg/kg) as a 90-minute intravenous infusion on Cycle 1 Day 1 (cycle length = 21 days), followed by every 3 weeks at a dose of 6 mg/kg as a 30 to 90-minute intravenous infusion until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

Also known as: Herceptin®, Herclon®

Pertuzumab in Combination with Trastuzumab and Docetaxel

Eligibility Criteria

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

You may qualify if:

• For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly-effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the participant and/or partner
• Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection; participants with measurable and/or non-measurable disease are eligible
• Known and documented HER2-positive
• Known and documented LVEF of at least 50 percent (%)
• Adequate organ function
• A negative serum beta-human chorionic gonadotropin (beta-HCG) test for women of childbearing potential (premenopausal, or less than \[\<\] 12 months of amenorrhea post-menopause, and women who have not undergone surgical sterilization \[absence of ovaries and/or uterus\]) within 7 days prior to the first dose of study treatment with the result available prior to first dosing

You may not qualify if:

• Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease
• Pregnant or lactating women
• Current clinical or radiographic evidence of central nervous system (CNS) metastases
• Disease progression while receiving or within 12 months of completion of trastuzumab and/or lapatinib treatment in the adjuvant or neo-adjuvant setting
• History of LVEF decline to below 50% during or after prior trastuzumab adjuvant or neo-adjuvant therapy

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

Tata Memorial Hospital; Dept of Medical Oncology

Mumbai, Maharashtra, 400012, India

Location

Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute

Mumbai, Maharashtra, 400053, India

Location

Jehangir Clinical Development Centre Pvt. Ltd; Cancer Research Room

Pune, Maharashtra, 411001, India

Location

Rajiv Gandhi Cancer Institute & Research Center

New Delhi, National Capital Territory of Delhi, 110 085, India

Location

Christian Medical College & Hospital; Medicine

Vellore, Tamil Nadu, 632004, India

Location

Indo-American Cancer Hospital & Research Center

Hyderabad, Telangana, 500034, India

Location

TATA Medical Centre; Medical Oncology

Kolkata, West Bengal, 700156, India

Location

M S Ramaiah Memorial Hospital

Bangalore, 560054, India

Location

MAX Balaji Hospital

Delhi, 110092, India

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; pertuzumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Anil Kukreja, MD

  Roche Products (India) Pvt. Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 15, 2015
• Study Start: August 17, 2015
• Primary Completion: September 26, 2018
• Study Completion: September 26, 2018
• Last Updated: October 29, 2019
• Results First Posted: October 29, 2019

Record last verified: 2019-10

Locations

IN (9)