HER2-positive Breast CancerPhase 2T-DM1NCT03530696

T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

A Phase 2 study testing Palbociclib and T-DM1 in people with HER2-positive Breast Cancer and Breast Cancer, run by University of Arizona at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a single arm, phase II study to evaluate if the combination of T-DM1 with palbociclib improves progression-free survival in patients with metastatic HER2 positive breast cancer. All patients will be treated with T-DM1 with palbociclib. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HER2-positive Breast Cancer, Breast Cancer, Breast Cancer Stage
What is being tested?: Palbociclib and T-DM1
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 55 participants
Where: 16 sitesUnited States
Study dates: 6 Dec 2018to 22 Dec 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Be informed of the investigational nature of the study and all pertinent aspects of the trial
Sign and provide written consent in accordance with institutional and federal guidelines.
ECOG Performance status of 0-2
Recurrent or metastatic HER2-positive breast cancer (HER2 positive is defined per ASCO-CAP guidelines)
Adequate cardiac reserve (EF≥50%)
Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN), bilirubin ≤ 2.0, and an SGOT/SGPT/alkaline phosphatase ≤ 2.0 x IULN

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Adequate bone marrow function (ANC ≥1000, Platelets ≥100,000/ml, Hemoglobin ≥10gm/dL)
Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
Been treated with pertuzumab previously (neoadjuvant or metastatic setting). Patients who weren't able to tolerate pertuzumab due to side effects can be eligible for study upon discussion with the study PI
No more than 2 lines of therapy in the metastatic disease setting

Who cannot join

HER2 negative tumors
Prior treatment with T-DM1
Prior treatment with CDK 4/6 inhibitors
Known active CNS metastases or carcinomatous meningitis. Patients with stable CNS 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 on study
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

Show all 9Show fewer

Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
Be pregnant or breast feeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment and must agree to use effective contraception during the period of therapy
Concurrent hormonal or other anti-neoplastic therapy is not allowed. Patients can receive supportive therapy like bone-directed therapy including bisphosphonates or denosumab

Trial locations and contacts

16 sites in 1 country.

City, postcode or hospital

16 sites in 1 country

United States16 sites

University of New Mexico
Albuquerque, New Mexico, 87131
University of Colorado Denver
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Cedar-Sinai
Beverly Hills, California, 90048
Roswell Park Comprehensive Cancer center
Buffalo, New York, 14263
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Cleveland Clinic
Cleveland, Ohio, 44195
JPS Health Network
Fort Worth, Texas, 76104
University of Wisconsin
Madison, Wisconsin, 53706
Yale Cancer Center
New Haven, Connecticut, 06519
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Oregon Health and Sciences University
Portland, Oregon, 97239
Mosaic Life Care
Saint Joseph, Missouri, 65406
Swedish Cancer Institute
Seattle, Washington, 98104
University of Washington
Seattle, Washington, 98195
University of Arizona Cancer Center
Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: A Single Arm Phase II Study to Evaluate Efficacy of T-DM1 With Palbociclib in the Treatment of Patients With Metastatic HER2 Positive Breast Cancer

Read the detailed description

This is a multi-center, single arm, phase II study of T-DM1 with palbociclib in the treatment of patients with metastatic HER2-positive breast cancer.

Hypotheses: Combination of T-DM1 with palbociclib improves progression free survival

Primary objective: Progression free survival of the combination of T-DM1 with palbociclib

Secondary objectives i) Response rates ii) Overall survival

Correlative objectives i) Investigate predictive biomarkers of response in blood and archived tumor tissue ii) Investigate mechanisms of resistance for palbociclib in blood and tumor tissue

Conditions: HER2-positive Breast Cancer, Breast Cancer, Breast Cancer Stage, Recurrent Breast Cancer, Metastatic Breast Cancer, HER2 Positive Breast Carcinoma
Being tested: Palbociclib, T-DM1
Keywords: Breast Cancer, HER2-positive, T-DM1, HER2-positive Breast Cancer, Recurrent Breast Cancer, Metastatic Breast Cancer
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PalbociclibDrug
Also called Ibrance
Palbociclib is to be taken orally on days 5-18 (14 days) of each cycle (each cycle length is 21 days). The starting dose will be 125mg.
T-DM1Drug
Also called Kadcyla
The recommended dose of T-DM1 is 3.6 mg/kg and is given as an intravenous infusion on Day 1 of every cycle (every 21 days).

Study groups in NCT03530696
Study group	Role	What they receive
T-DM1 with palbociclib	Experimental	T-DM1 is given intravenously every 21 days (day 1 of each cycle) Palbociclib is administered orally on days 5-18 of each cycle Receives: Drug: Palbociclib; Drug: T-DM1
Single Agent T-DM1	Experimental	T-DM1 is given intravenously every 21 days (day 1 of each cycle) Receives: Drug: T-DM1

What is being measured

The primary outcome is the main question the study is designed to answer.

Estimate Progression-free Survival
Progression Free Survival (PFS) is defined as the time from date of first treatment to the date of investigator-determined objective disease progression as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 or death from any cause. Per RECIST 1.1 for target lesions: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Patients who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post initiation (that is post baseline) radiographic assessment is available.
Measured: Up to 4 years

Secondary outcomes (2)

Number of Participants With Response
Per RECIST 1.1 for target lesions: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Overall response rate (ORR) is defined as the proportion of patients with CR or PR per RECIST 1.1. Disease control rate (DCR) is defined as the proportion of patients with CR, PR or SD per RECIST 1.1. The data shown is the number of participants with ORR, DCR, CR, PR, PD, and SD.
Measured: Up to 4 years
Estimate Overall Survival
Estimate overall survival of T-DM1+Palbociclib treatment regimen. Overall survival (OS) is defined as the time from date of first treatment to date of death due to any cause. Patients last known to be alive are censored at their last contact date.
Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Dec 201822 Dec 2022

First posted21 May 2018
Study start6 Dec 2018
Primary completion22 Dec 2022
Study completion22 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 55 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03530696
Sponsor's protocol ID: 29747
Other IDs: T-DM1, Palbo T-DM1
Acronym: T-DM1
Status last verified: Jul 2024
First submitted: 8 May 2018
Last updated: 13 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Arm Phase II Study to Evaluate Efficacy of T-DM1 With Palbociclib in the Treatment of Patients With Metastatic HER2 Positive Breast Cancer
ClinicalTrials.gov ID: NCT03530696
Acronym / sponsor ID: T-DM1 / 29747
Conditions: HER2-positive Breast Cancer, Breast Cancer, Breast Cancer Stage, Recurrent Breast Cancer, Metastatic Breast Cancer, HER2 Positive Breast Carcinoma
Keywords: Breast Cancer, HER2-positive, T-DM1, HER2-positive Breast Cancer, Recurrent Breast Cancer, Metastatic Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 55 participants (actual)
Lead sponsor: University of ArizonaUniversity, hospital or other
Collaborators: Pfizer
Study start: 6 Dec 2018 (actual)
Primary completion: 22 Dec 2022 (actual)
Study completion: 22 Dec 2022 (actual)
First posted: 21 May 2018 (actual)
Results: Posted 24 Jul 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This is a multi-center, single arm, phase II study of T-DM1 with palbociclib in the treatment of patients with metastatic HER2-positive breast cancer.

Hypotheses: Combination of T-DM1 with palbociclib improves progression free survival

Primary objective: Progression free survival of the combination of T-DM1 with palbociclib

Secondary objectives i) Response rates ii) Overall survival

Correlative objectives i) Investigate predictive biomarkers of response in blood and archived tumor tissue ii) Investigate mechanisms of resistance for palbociclib in blood and tumor tissue

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
T-DM1 with palbociclib	Experimental	Drug: Palbociclib, Drug: T-DM1T-DM1 is given intravenously every 21 days (day 1 of each cycle) Palbociclib is administered orally on days 5-18 of each cycle
Single Agent T-DM1	Experimental	Drug: T-DM1T-DM1 is given intravenously every 21 days (day 1 of each cycle)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Be informed of the investigational nature of the study and all pertinent aspects of the trial
Sign and provide written consent in accordance with institutional and federal guidelines.
ECOG Performance status of 0-2
Recurrent or metastatic HER2-positive breast cancer (HER2 positive is defined per ASCO-CAP guidelines)
Adequate cardiac reserve (EF≥50%)

Key exclusion criteria (9 listed)

HER2 negative tumors
Prior treatment with T-DM1
Prior treatment with CDK 4/6 inhibitors
Known active CNS metastases or carcinomatous meningitis. Patients with stable CNS 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 on study
Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PalbociclibAlso: IbrancePalbociclib is to be taken orally on days 5-18 (14 days) of each cycle (each cycle length is 21 days). The starting dose will be 125mg.	Drug	T-DM1 with palbociclib
T-DM1Also: KadcylaThe recommended dose of T-DM1 is 3.6 mg/kg and is given as an intravenous infusion on Day 1 of every cycle (every 21 days).	Drug	Single Agent T-DM1, T-DM1 with palbociclib

Primary outcome

Estimate Progression-free Survival
Time frame: Up to 4 years
Progression Free Survival (PFS) is defined as the time from date of first treatment to the date of investigator-determined objective disease progression as defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 or death from any cause. Per RECIST 1.1 for target lesions: Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD) is at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Patients who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post initiation (that is post baseline) radiographic assessment is available.

2 secondary outcomes

Number of Participants With Response
Time frame: Up to 4 years
Estimate Overall Survival
Time frame: Up to 4 years

Results and safety

Results posted to the registry on 24 Jul 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
T-DM1 With Palbociclib	39	38
Single Agent T-DM1	16	14

Primary outcome: Estimate Progression-free Survival

Time frame: Up to 4 years. Median (95% Confidence Interval). Unit: Months

Measure	T-DM1 With Palbociclib n = 36	Single Agent T-DM1 n = 11
Value	16.9 (8.3 to NA)	8.3 (2.7 to 8.8)

Population analysed: Number of patients included for PFS analysis: T-DM1 with Palbociclib Arm: n=36 T-DM1 Arm: n=11 5 patients lack data on response because they discontinued study participation (or withdrew consent) before the first scan. Thus, the final sample size for responses is n = 47.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) were assessed and collected starting from day 1 of study treatment and continued through the 30 day follow-up period after treatment discontinuation, up to 4 years.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
T-DM1 With Palbociclib	8 of 38 (21.1%)	38 of 38 (100%)	5 of 38
Single Agent T-DM1	3 of 14 (21.4%)	14 of 14 (100%)	4 of 14

Limitations and caveats (from the sponsor): The study was originally a 2-arm, randomized study (T-DM1 with Palbociclib and single agent T-DM1); however, due to the COVID-19 pandemic restrictions and slow accrual, the study design was updated to a single arm study of T-DM1 with Palbociclib.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pavani Chalasani, MD principal investigator

The University of Arizona Cancer Center

16 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palbociclib and T-DM1 in people with HER2-positive Breast Cancer and Breast Cancer, run by University of Arizona at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimate Progression-free Survival (time frame: Up to 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03530696.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2024.