Phase 1b Study of PD-0332991 in Combination With T-DM1(Trastuzumab-DM1)

NCT01976169 | Completed Phase 1 DMC

• 1 other identifier: STU 042013-042
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Standard of care: Treatment with Trastuzumab Experimental: 21-Day Cycle of Combination therapy with T-DM1 intravenously on Day 1 and oral PD-0332991 on Days 5-18 Study Design and Methodology: This is a phase 1B inter-patient dose escalation study of PD-0332991 in combination with T-DM1 in patients with recurrent or metastatic HER2-positive breast cancer after prior trastuzumab or other HER2-directed therapies. The subjects will be administered T-DM1 by intravenous infusion at 3.6 mg/kg for 90 minutes on day 1 of each 21 day cycle. Infusion timing may vary from 30-90 minutes depending on how well the subject tolerates the treatment. A standard 3+3 trial design will be used for PD-0332991 dose escalation cohorts.The dosing of PD-0332991 will be divided into 3 cohorts, the subjects will receive PD-0332991 on days 5-18 of each 21 day cycle. Cohort 1 : PD-0332991 - 100 mg daily (oral) Cohort 2 : PD-0332991 - 150 mg daily (oral) Cohort 3 : PD-0332991 - 200 mg daily (oral) The 3+3 design entails that if one patient out of the first three patients has a DLT, up to three additional patients will be entered at that dose level Treatment cycles will continue until disease progression or withdrawal from study.

Conditions

Advanced Breast Cancer

Keywords

Breast Cancer; Advanced Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  A standard 3+3 trial design will be used for PD-0332991 dose escalation cohorts.The dosing of PD-0332991 will be divided into 3 cohorts, the subjects will receive PD-0332991 on days 5-18 of each 21 day cycle. Cohort 1 : PD-0332991 - 100 mg daily (oral) Cohort 2 : PD-0332991 - 150 mg daily (oral) Cohort 3 : PD-0332991 - 200 mg daily (oral)

  42 days at the end of Cycle 2

• Dose Limiting Toxicities (DLT)

  The 3+3 design entails that if one patient out of the first three patients has a DLT, up to three additional patients will be entered at that dose level

  42 days at the end of Cycle 2

Study Arms (1)

PD-0332991 and T-DM1

EXPERIMENTAL

The subjects will be administered T-DM1 by intravenous infusion at 3.6 mg/kg for 90 minutes on day 1 of each 21 day cycle. Infusion timing may vary from 30-90 minutes depending on how well the subject tolerates the treatment. A standard 3+3 trial design will be used for PD-0332991 dose escalation cohorts.The dosing of PD-0332991 will be divided into 3 cohorts, the subjects will receive PD-0332991 on days 5-18 of each 21 day cycle. Cohort 1 : PD-0332991 - 100 mg daily (oral) Cohort 2 : PD-0332991 - 150 mg daily (oral) Cohort 3 : PD-0332991 - 200 mg daily (oral)

Drug: PD-0332991 and T-DM1

Interventions

PD-0332991 and T-DM1 DRUG

The subjects will be administered T-DM1 by intravenous infusion at 3.6 mg/kg for 90 minutes on day 1 of each 21 day cycle. Infusion timing may vary from 30-90 minutes depending on how well the subject tolerates the treatment. A standard 3+3 trial design will be used for PD-0332991 dose escalation cohorts.The dosing of PD-0332991 will be divided into 3 cohorts, the subjects will receive PD-0332991 on days 5-18 of each 21 day cycle. Cohort 1 : PD-0332991 - 100 mg daily (oral) Cohort 2 : PD-0332991 - 150 mg daily (oral) Cohort 3 : PD-0332991 - 200 mg daily (oral)

Also known as: KADCYLA=T-DM1, Palbociclib=PD-0332991

PD-0332991 and T-DM1

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must be informed about the study and have signed a current IRB (Institutional Review Board) approved informed consent.
• \. All subjects must have recurrent or metastatic HER2-positive breast cancer. diagnosed by biopsy.
• \. All subjects must have previously received trastuzumab or other HER2 targeted therapies.
• \. Subjects must have a performance status of ≤ 2 on the ECOG (Eastern Cooperative Oncology Group)Performance scale.
• \. Subjects must have bilirubin \<1.5 mg/dl, transaminases \<2.5x upper limit of normal, albumin \>3gm/dl, creatinine \<1.3mg/dl, adequate cardiac reserve (EF\>50%), ANC (Absolute neutrophil count) \>1,000/mcL (microliter), and Platelets \>100,000/mcL.
• \. Must be willing to be treated at the University of Texas Southwestern Hospital, University of Pennsylvania and affiliated clinics.
• \. Subjects must be willing to use an approved form of birth control while on this study and for 90 days after completion.
• \. Age \> 18 years. 10. Subject must be able to swallow capsules and have no surgical or anatomic condition that will preclude the subject from swallowing and absorbing oral medications on an ongoing basis.

You may not qualify if:

• \. Chemotherapy, radiotherapy or hormonal therapy within 3 weeks ( 6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who have not recovered from the adverse events to \< grade 2 due to previous agents administered more than 4 weeks prior to Study Day 1.
• \. Subjects less than 4 weeks post major surgery. 3. Known active CNS metastases or carcinomatous meningitis. Subjects with CNS (Central Nervous System) metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. However, oral corticosteroids for control of CNS symptoms are not allowed.
• \. Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs.
• \. Uncontrolled systemic illness, including but not limited to ongoing or active infection.
• \. Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months.
• \. Baseline neuropathy \>grade 1. 8. Known positive for human immunodeficiency virus (HIV). Baseline HIV screening is not required.
• \. Pregnant or breast-feeding subjects. 10. Subjects who are unable or unwilling to abide by the study protocol or to cooperate fully with the investigator or designee.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Pfizer: collaborator
• University of Pennsylvania: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Barbara Haley, MD

  Internal Medicine Hematology Oncology

  PRINCIPAL INVESTIGATOR

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: October 29, 2013
• First Posted: November 5, 2013
• Study Start: January 24, 2014
• Primary Completion: May 19, 2021
• Study Completion: May 19, 2021
• Last Updated: February 8, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)