A Study of Perjeta (Pertuzumab) in Combination With Herceptin (Trastuzumab) in Participants With Metastatic Breast Cancer

NCT01674062 | Completed Phase 2 Results

• 2 other identifiers: BO179292005-003493-19
• Study Type: interventional
• Target: 95
• Locations: 5 countries
• Sites: 20

Brief Summary

This study will evaluate the efficacy and safety of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) in participants with metastatic breast cancer who have progressed on trastuzumab-based therapy (Cohorts 1 and 2), and will make a preliminary assessment of the efficacy and safety of single-agent pertuzumab (Cohort 3). Objective response rate and clinical benefit will be assessed. Pertuzumab will be administered at an initial dose of 840 milligrams (mg) intravenously (IV) on Day 1, followed by 420 mg IV every 3 weeks. Trastuzumab will be administered at the same schedule the participant was following before entry into the study. An additional cohort of participants at certain centers will receive pertuzumab monotherapy at an initial dose of 840 mg IV on Day 1, followed by 420 mg IV every 3 weeks. These participants may have trastuzumab added to the regimen in the event of progression during single-agent pertuzumab treatment.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 During Dual-Agent Treatment

  Tumor response was assessed using RECIST version 1.0 to determine the objective response (OR) rate, or the percentage of participants with either confirmed CR or PR. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30 percent (%) decrease in the sum of the longest diameter compared to Baseline. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The OR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.

  Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)

• Cohorts 1 and 2: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or Stable Disease (SD) According to RECIST Version 1.0 During Dual-Agent Treatment

  Tumor response was assessed using RECIST version 1.0 to determine the clinical benefit response (CBR) rate, or the percentage of participants with either confirmed CR or PR, or SD lasting at least 6 months. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Response was to be confirmed a minimum of 4 weeks after the initial response was documented. The CBR rate was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.

  Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)

Secondary Outcomes (9)

• Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR or PR According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab

  Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)

• Cohort 3: Percentage of Participants With a Confirmed Best Overall Response of CR, PR, or SD According to RECIST Version 1.0 During Single-Agent Treatment With Pertuzumab

  Up to approximately 7.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)

• Cohorts 1 and 2: Duration of Response According to RECIST Version 1.0

  Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)

• Cohorts 1 and 2: Time to Objective Response According to RECIST Version 1.0

  Up to approximately 21 months (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression; final analysis using February 2008 cutoff date)

• Cohorts 1 and 2: Percentage of Participants With Disease Progression According to RECIST Version 1.0

  Up to approximately 9.5 years (at Screening; on Day 15 of Cycles 2, 4, 6, and 8 [cycle length 3 weeks]; then every 3 months until disease progression)

Study Arms (2)

Pertuzumab + Trastuzumab (Cohorts 1 and 2)

EXPERIMENTAL

Females with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer will receive dual-agent treatment with pertuzumab and trastuzumab. Trastuzumab will be administered IV as 2 milligrams per kilogram (mg/kg) once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, beginning on Day 2 of Cycle 1. Thereafter, both medications will be administered on Day 1 of each 3-week cycle. Treatment will continue for a minimum of 8 cycles and may be extended until disease progression, intolerable toxicity, or death.

Drug: Pertuzumab; Drug: Trastuzumab

Pertuzumab +/- Trastuzumab (Cohort 3)

EXPERIMENTAL

Females with HER2-positive metastatic breast cancer will receive single-agent treatment with pertuzumab. Pertuzumab will be administered IV at a loading dose of 840 mg followed by a standard dose of 420 mg every 3 weeks, administered on Day 1 of each 3-week cycle. Participants with documented disease progression may have trastuzumab added to the regimen, per the dosing schedule described for Cohorts 1 and 2, to receive dual-agent treatment until disease progression, intolerable toxicity, or death.

Drug: Pertuzumab; Drug: Trastuzumab

Interventions

Pertuzumab DRUG

Loading dose 840 mg IV on Day 2 of Cycle 1, followed by 420 mg every 3 weeks thereafter, until disease progression or unacceptable toxicity.

Also known as: Perjeta

Pertuzumab + Trastuzumab (Cohorts 1 and 2); Pertuzumab +/- Trastuzumab (Cohort 3)

Trastuzumab DRUG

2 mg/kg IV once weekly, or as 6 mg/kg every 3 weeks, beginning on Day 1 of Cycle 1 and on Day 1 of each 3-week cycle thereafter until disease progression or unacceptable toxicity.

Also known as: Herceptin

Pertuzumab + Trastuzumab (Cohorts 1 and 2); Pertuzumab +/- Trastuzumab (Cohort 3)

Eligibility Criteria

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

You may qualify if:

• Females greater than or equal to (≥) 18 years of age, with histologically-confirmed HER2-positive breast cancer
• Metastatic breast cancer, with progression on trastuzumab-based therapy as last treatment for metastatic disease
• Less than or equal to (≤) 3 chemotherapy regimens prior to study entry
• Last trastuzumab dose ≤9 weeks before study entry for participants receiving pertuzumab + trastuzumab, and ≥4 weeks for participants receiving pertuzumab monotherapy
• Left ventricular ejection fraction ≥55% at study entry

You may not qualify if:

• Previous treatment with an anti-cancer vaccine or any targeted therapy other than trastuzumab
• Brain metastases
• History of any cardiac adverse event related to trastuzumab therapy
• Any other malignancy in the last 5 years, except for basal cell cancer or cancer in situ of the cervix

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (20)

Unknown Facility

Edmonton, Alberta, T6G 1Z2, Canada

Location

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Vancouver, British Columbia, V5Z 4E6, Canada

Location

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London, Ontario, N6A 4L6, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Besançon, 25030, France

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Dijon, 21079, France

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Lille, 59020, France

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Montpellier, 34298, France

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Modena, Emilia-Romagna, 41100, Italy

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Parma, Emilia-Romagna, 43100, Italy

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Milan, Lombardy, 20133, Italy

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Barcelona, Barcelona, 08003, Spain

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Barcelona, Barcelona, 08035, Spain

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Valencia, Valencia, 46009, Spain

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Valencia, Valencia, 46010, Spain

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Edinburgh, EH4 2XU, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Northwood, HA6 2RN, United Kingdom

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Truro, TR1 3LJ, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Although the study was designed as single-arm study, as reflected in the study title, an additional cohort was opened to evaluate the efficacy and safety of single-agent pertuzumab.

Results Point of Contact

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

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2012
• First Posted: August 28, 2012
• Study Start: May 1, 2006
• Primary Completion: February 1, 2008
• Study Completion: September 1, 2015
• Last Updated: August 22, 2016
• Results First Posted: September 11, 2015

Record last verified: 2016-07

Locations

IT (3); GB (4); ES (4); FR (4); CA (5)