1303GCC: Trastuzmab & Pertuzumab With Hormonal Therapy or Chemotherapy in Women Aged 60 and Over.

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02000596
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 2
• Location: 1
• Arms: 3
• Duration (Months): 24
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a phase II study that combines Trastuzumab with Pertuzumab to see how it works in women age greater than 60 who have been diagnosed with HER2/neu overexpressed locally advanced and/or metastatic breast carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Trastuzumab plus Pertuzumab; Drug: Hormonal Therapy with Anastrozole and Fulvestrant; Drug: Chemotherapy with Eribulin	Phase 2

Detailed Description

Currently available standard therapies for HER2 overexpressed metastatic breast cancers (MBC) include treatments with chemotherapy or hormonal therapy, alone or in combination with medications that target HER2 gene, such as Trastuzumab or Pertuzumab. This study will examine the effect of treating HER2 overexpressed MBC with the combination of Trastuzumab plus Pertuzumab, without hormonal or chemotherapy, as a first line treatment. If patients progress on this treatment, they will receive hormonal or chemotherapy in addition to the Trastuzumab plus Pertuzumab treatment. The objective is to see how the overall response rate for this treatment compares to other first line treatments in the same patient population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 1303GCC: Phase II Study of Trastuzumab and Pertuzumab Alone and in Combination With Hormonal Therapy or Chemotherapy in Women Aged 60 and Over With HER2/Neu Overexpressed Locally Advanced and/or Metastatic Breast Carcinoma
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: T+P Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy)	Drug: Trastuzumab plus Pertuzumab
Experimental: Cohort 2 - Arm A Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR +	Drug: Trastuzumab plus Pertuzumab; Drug: Hormonal Therapy with Anastrozole and Fulvestrant; Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days; Other Names: Anastrozole (Arimidex) Fulvestrant (Faslodex)
Experimental: Cohort 2 - Arm B Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR -	Drug: Trastuzumab plus Pertuzumab; Drug: Chemotherapy with Eribulin

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) in Patients [Participants were staged every two cycles for the duration of the study participation ( CR+PR+SD=ORR), up to 11 months]

   Defined as the total of complete response (CR) defined as a disappearance of all target lesions, partial response (PR) defined as >= 30% decrease in the sum of the longest diameter of target lesions, and stable disease (SD) >= 27 weeks among the total number of participants as defined by the Response Evaluation in Solid Tumors (RECIST) 1.1 response criteria.

Secondary Outcome Measures

1. Progression-free Survival (PFS) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months]

   Progression Free Survival in treatment cohorts 1 and 2 as well as arms A and B from the time on study until progression of disease or death

2. Overall Survival (OS) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, an average of 2 years.]

   Overall survival (OS) in treatment cohorts 1 and 2 as well as arms A and B from the time on study until death

3. Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0 [Participants were followed during the study and for 30 days after completion of the study treatment, up to 12 months]

   the safety and tolerability of Trastuzumab and Pertuzumab alone and in combination with hormonal therapy or single agent chemotherapy. in HER2+ MBC patients

4. Quality of Life Via Patient-reported Outcomes [Duration of study, participants were followed every cycle up to 11 months.]

   quality of life and treatment side effects via patient-reported and investigator reported outcomes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Women ≥60 Years of Age.

2. Histologically confirmed, locally advanced (T4 primary tumor and stage IIIB or IIIC disease) or metastatic breast cancer that progressed after treatment with standard treatment regimens in the adjuvant or neoadjuvant setting.

3. Prior treatment with trastuzumab and/or lapatinib in the neo-adjuvant or adjuvant setting is allowed but not required. Lapatininb has to be discontinued > 21 days before the initiation of the T+P study treatments.

4. Up to 3 prior chemo regimens for treatment of metastatic disease are allowed as long as the study subject is acceptable for study treatment with chemo required on this study in cohort 2 at progression on T+P.

5. Patients may have had prior hormonal therapy with any hormonal agents as per section 3.1.5 of this protocol.

6. Zometa or denosumab can be continued as per standard of care as long as started before the study treatment is started.

7. HER2 positive breast cancer, as defined in Section 3.3 of this protocol

8. Must have measurable or evaluable disease according to RECIST 1.1 criteria.

9. Lab values obtained ≤7 days prior to registration as indicated in 3.1.9 of this protocol.

10. ECOG Performance Status (PS) of 0, 1 or 2.

11. LVEF at least 50% as determined by MUGA or ECHO.

12. Life expectancy >3 months.

13. Written informed consent.

14. Willingness to return to study site for treatment and follow-up.

15. Normal QTc interval defined on EKG as QTc ≤ 440 msec.

16. Postmenopausal women defined in section 3.1.16 of this protocol.

Exclusion Criteria:

1. Stage III or IV cancer, other than breast cancer, in ≤5 years prior to registration.

2. Actively being treated for other malignancy.

3. New York Heart Association Class III or IV cardiovascular disease.

4. History of coronary heart failure (CHF)

5. Current use of drugs known to prolong the QTc interval including Class Ia and III antiarrhythmics or history of congenital long QTc syndrome.

6. Evidence of active brain metastasis including leptomeningeal involvement.

7. Major surgery, chemotherapy, hormonal or immunologic therapy ≤3 weeks prior to registration.

8. Radiotherapy ≤3 weeks prior to registration, except if to a non-target lesion only.

9. Prior treatment with Pertuzumab, Eribulin, Fulvestrant or Anastrozole.

10. Uncontrolled illness.

11. Co-morbid systemic illnesses or other severe concurrent disease. See section 3.2.11.

12. Currently receiving treatment in a different clinical study in which investigational procedures are performed or investigational therapies are administered.

13. Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive.

14. International normalized ratio (INR), activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on anticoagulation medication)

15. Receipt of intravenous (IV) antibiotics for infection within 7 days prior to enrollment into the study.

16. Current chronic daily treatment with corticosteroids. See section 3.2.16 of this protocol.

17. Known hypersensitivity to any of the study treatments or to excipients of recombinant human or humanized antibodies.

18. History of receiving any investigational treatment within 28 days prior to enrollment into the study.

19. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland Marlene & Stewart Greenebaum Cancer Center	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore
• Genentech, Inc.

Investigators

• Principal Investigator: Katherine Tkaczuk, MD, University of Maryland Greenebaum Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT02000596
• Other Study ID Numbers: HP-00054959; 1303GCC; GCC1303
• First Posted: Dec 4, 2013
• Last Update Posted: May 27, 2022
• Last Verified: May 1, 2022

• Keywords provided by University of Maryland, Baltimore: HER2 overexpressed; Metastatic Breast Cancer; Elderly
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Pertuzumab; Fulvestrant; Anastrozole

Study Results

Participant Flow

Arm/Group Title	Cohort 1: T+P	Cohort 2 - Arm A	Cohort 2 - Arm B
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab	Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days	Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin
Period Title: Cohort 1
STARTED	2	0	0
COMPLETED	2	0	0
NOT COMPLETED	0	0	0
Period Title: Cohort 1
STARTED	0	0	2
COMPLETED	0	0	2
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1: T+P	Cohort 2 - Arm A	Cohort 2 - Arm B	Total
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab	Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days	Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin	Total of all reporting groups
Overall Participants	2	0	0	2
Age (Count of Participants)
<=18 years	0 0%	0 NaN	0 NaN
Between 18 and 65 years	2 100%	0 NaN	2 Infinity
>=65 years	0 0%	0 NaN	0 NaN
Sex: Female, Male (Count of Participants)
Female	2 100%	0 NaN	2 Infinity
Male	0 0%	0 NaN	0 NaN
Race/Ethnicity, Customized (Count of Participants)
White/ Non-Hispanic	2 100%	0 NaN	2 Infinity
Region of Enrollment (participants) [Number]
United States	2 100%	2 Infinity

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) in Patients
Description	Defined as the total of complete response (CR) defined as a disappearance of all target lesions, partial response (PR) defined as >= 30% decrease in the sum of the longest diameter of target lesions, and stable disease (SD) >= 27 weeks among the total number of participants as defined by the Response Evaluation in Solid Tumors (RECIST) 1.1 response criteria.
Time Frame	Participants were staged every two cycles for the duration of the study participation ( CR+PR+SD=ORR), up to 11 months

Outcome Measure Data

Analysis Population Description

Participants started in "Cohort 1: T+P" Arm/Group and continued in "Cohort 2 Arm B" due to progressive disease

Arm/Group Title	Cohort 1: T+P	Cohort 2 - Arm A	Cohort 2 - Arm B
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab	Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days	Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin
Measure Participants	2	0	2
Complete Response (CR)	0 0%	0 NaN
Partial Response (PR)	1 50%	0 NaN
Stable Disease (SD)	1 50%	2 Infinity

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression Free Survival in treatment cohorts 1 and 2 as well as arms A and B from the time on study until progression of disease or death
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 11 months

Outcome Measure Data

Analysis Population Description

No participants were enrolled in Cohort 2- Arm A

Arm/Group Title	Cohort 1: T+P	Cohort 2 - Arm A	Cohort 2 - Arm B
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab	Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days	Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin
Measure Participants	2	0	2
Subject 1	6	12
Subject 2	24	24

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) in treatment cohorts 1 and 2 as well as arms A and B from the time on study until death
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, an average of 2 years.

Outcome Measure Data

Analysis Population Description

Participants started in "Cohort 1: T+P" Arm/Group and continued in "Cohort 2 Arm B" due to progressive disease. The analysis below reflects Cohort 2 only

Arm/Group Title	Cohort 1: T+P	Cohort 2 - Arm A	Cohort 2 - Arm B
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab	Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days	Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin
Measure Participants	0	0	2
Subject 1	25
Subject 2	14

4. Secondary Outcome

Title	Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0
Description	the safety and tolerability of Trastuzumab and Pertuzumab alone and in combination with hormonal therapy or single agent chemotherapy. in HER2+ MBC patients
Time Frame	Participants were followed during the study and for 30 days after completion of the study treatment, up to 12 months

Outcome Measure Data

Analysis Population Description

No participants were enrolled in Cohort 2- Arm A

Arm/Group Title	Cohort 1: T+P	Cohort 2 - Arm A	Cohort 2 - Arm B
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab	Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days	Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin
Measure Participants	2	0	2
participant 1	5 250%	2 Infinity
participant 2	5 250%	8 Infinity

5. Secondary Outcome

Title	Quality of Life Via Patient-reported Outcomes
Description	quality of life and treatment side effects via patient-reported and investigator reported outcomes
Time Frame	Duration of study, participants were followed every cycle up to 11 months.

Outcome Measure Data

Analysis Population Description

Two patients were enrolled, no data was analyzed.

Arm/Group Title	Cohort 1: T+P	Cohort 2 - Arm A	Cohort 2 - Arm B
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab	Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days	Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin
Measure Participants	0	0	0

Adverse Events

Time Frame	up to 24 months
Adverse Event Reporting Description	There were no participants enrolled in Cohort 2 - Arm A, therefore, the at risk population for all-cause mortality, SAEs, and AEs are zero.
Arm/Group Title	Cohort 1: T+P		Cohort 2 - Arm A		Cohort 2 - Arm B
Arm/Group Description	Trastuzumab plus Pertuzumab as first line treatment for HER2 overexpressed Metastatic Breast Cancer (without hormonal therapy or chemotherapy) Trastuzumab plus Pertuzumab		Hormonal Therapy with Anastrozole and Fulvestrant in addition Trastuzumab plus Pertuzumab for women who progressed on T+P alone, and who are ER/PR + Trastuzumab plus Pertuzumab Hormonal Therapy with Anastrozole and Fulvestrant: Anastrozole 1mg by mouth daily FULVESTRANT 500mg i.m. D1, D15, D28 then every 28-30 days		Chemotherapy with Eribulin in addition to Trastuzumab plus Pertuzumab for women who progressed on T+P alone and who are ER/PR - Trastuzumab plus Pertuzumab Chemotherapy with Eribulin
All Cause Mortality
	Cohort 1: T+P		Cohort 2 - Arm A		Cohort 2 - Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		0/0 (NaN)		2/2 (100%)
Serious Adverse Events
	Cohort 1: T+P		Cohort 2 - Arm A		Cohort 2 - Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/0 (NaN)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: T+P		Cohort 2 - Arm A		Cohort 2 - Arm B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		0/0 (NaN)		2/2 (100%)
Blood and lymphatic system disorders
Anemia	0/2 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1
Gastrointestinal disorders
Reflux	0/2 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1
Taste Changes	0/2 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1
General disorders
Fatigue	2/2 (100%)	2	0/0 (NaN)	0	0/2 (0%)	0
Fatigue	0/2 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1
Rigors	1/2 (50%)	1	0/0 (NaN)	0	0/2 (0%)	0
Hepatobiliary disorders
elevated AST	1/2 (50%)	1	0/0 (NaN)	0	1/2 (50%)	1
elevated ALT	0/2 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
muscle aches or neck aches	1/2 (50%)	1	0/0 (NaN)	0	0/2 (0%)	0
Nervous system disorders
smell aversion	1/2 (50%)	1	0/0 (NaN)	0	0/2 (0%)	0
Paresthia	1/2 (50%)	1	0/0 (NaN)	0	0/2 (0%)	0
Insomnia	0/2 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1
Skin and subcutaneous tissue disorders
Itching	1/2 (50%)	1	0/0 (NaN)	0	0/2 (0%)	0
Itching	0/2 (0%)	0	0/0 (NaN)	0	1/2 (50%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.