Phase I/IIa Trial of Gemcitabine Plus Trastuzumab and Pertuzumab in Previously Treated Metastatic HER2+ Breast Cancer

NCT02139358 | Completed Phase 1 Results

• 2 other identifiers: MCC-17656ML28939
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and activity of gemcitabine plus trastuzumab and pertuzumab in patients with metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer who have progressed on at least one prior line of chemotherapy plus HER2 targeted agent such as T-DM1, trastuzumab, or lapatinib.

Conditions

Breast Cancer

Keywords

Breast - Female; Metastatic; HER2+

Outcome Measures

Primary Outcomes (2)

• Phase I: Recommended Phase II Dose (RP2D)

  The RP2D dose in mg/m\^2 of gemcitabine along with standard doses of pertuzumab (840 mg loading/420 mg maintenance) and Herceptin (8 mg/kg loading, 6 mg/kg maintenance). Safety data to be described using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 terminology. Any participant who receives any dose of the study treatment will be evaluated for the safety/toxicity endpoints in the trial.

  6 Months

• Phase II: Objective Response Rate (ORR)

  Objective Response Rate: Response according to Response Evaluation in Solid Tumors (RECIST) 1.1 for the combination of gemcitabine+trastuzumab+pertuzumab at the recommended phase II dose. Complete Response (CR): Disappearance of all evidence of tumor for at least two cycles of therapy. Tumor markers must be normal. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking a reference the baseline sum longest diameter. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the beginning of treatment or the appearance of one or more new lesions.

  Up to 36 Months

Secondary Outcomes (2)

• Phase II: Progression Free Survival (PFS)

  Up to 12 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (1)

Dose Escalation / Phase II Treatment

EXPERIMENTAL

Single arm, non-randomized, open label phase I/II multisite Simon two stage minimax trial. Gemcitabine plus trastuzumab and pertuzumab.

Drug: Gemcitabine; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

Gemcitabine DRUG

The Phase I trial will start at the recommended phase II dose (RP2D) for gemcitabine but will have a de-escalation dose levels in the event that an unacceptable toxicity requires dose reduction. Dose level 0 = gemcitabine (1200 mg/m2) IV D1,8 q21 days; Dose level -1 = gemcitabine (1000 mg/m\^2) IV D1,8 q21 days; Dose level -2 = gemcitabine (850 mg/m\^2) IV D1,8 q21 days. The RP2D will be the dose level where 0-1 dose limiting toxicities (DLTs) in six patients occur.

Also known as: GEMZAR®

Dose Escalation / Phase II Treatment

Trastuzumab DRUG

Trastuzumab will be given using an 8 mg/kg loading dose on cycle one, day one (C1D1), followed by 6 mg/kg IV on subsequent cycles every (q) 21 days.

Also known as: Herceptin®

Dose Escalation / Phase II Treatment

Pertuzumab DRUG

Pertuzumab will be given using an 840 mg IV loading dose on C1D1, followed by 420 mg IV on subsequent cycles q 21 days.

Also known as: PERJETA®

Dose Escalation / Phase II Treatment

Eligibility Criteria

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

You may qualify if:

• Adult males or females (aged 18 or older) with histologically confirmed, metastatic human epidermal growth factor receptor 2 (HER2)+ (by immunohistochemistry (IHC) 3+ or fluorescence in situ hydridization (FISH) ratio ≥ 2.0) breast cancer
• Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy such as trastuzumab and/or pertuzumab in the metastatic setting. T-DM1 would count as a line of therapy and patients previously treated with T-DM1 are eligible.
• Have not been treated with gemcitabine in the metastatic setting
• Measurable disease per Response Evaluation in Solid Tumors (RECIST) 1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 2≤
• Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline as determined by either echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
• Adequate bone marrow function as indicated by the following: absolute neutrophil count (ANC) \>1500/µL; Platelets ≥100,000/µL; Hemoglobin \>10 g/dL
• Adequate renal function, as indicated by creatinine ≤1.5x upper limit of normal (ULN)
• Adequate liver function, as indicated by bilirubin ≤1.5x ULN, aspartic transaminase (AST) or alanine transaminase (ALT) \<2x ULN unless related to metastatic breast cancer to the liver (in which case AST/ALT \< 5x ULN is allowed).
• Signed informed consent
• Adequate birth control in sexually active women of childbearing potential

You may not qualify if:

• Active uncontrolled infection or major concurrent illness which in the opinion of the investigator would render the participant unsafe to proceed with the study
• Uncontrolled central nervous system (CNS) metastases. Treated, non-progressing CNS disease (documented by brain magnetic resonance imaging \[MRI\]) off corticosteroids for at least 1 month potential participants are eligible.
• Women who are pregnant or lactating
• Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin)
• Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
• Other concomitant active malignancies
• History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
• Ejection fraction \<50% or below the lower limit of the institutional normal range, whichever is lower
• Hypersensitivity to any of the study medications
• Untreated psychiatric conditions preventing informed consent

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Genentech, Inc.: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Gemcitabine; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Hatem Soliman
• Organization: H. Lee Moffitt Cancer Center and Research Institute

hatem.soliman@moffitt.org

813-745-4933

Study Officials

• Hatem Soliman, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 15, 2014
• Study Start: September 5, 2014
• Primary Completion: April 24, 2018
• Study Completion: March 16, 2020
• Last Updated: February 4, 2021
• Results First Posted: July 20, 2018

Record last verified: 2021-02

Locations

US (1)