Breast CancerPhase 1NCT01199367
Safety, Tolerability, and Efficacy Study in Subjects With Advanced or Metastatic Breast Cancer
A Phase 1 study testing KW-2450 in combination with lapatinib and letrozole in people with Breast Cancer, run by Kyowa Kirin Co., Ltd. at 5 sites in United States.
Trial summary
This study will determine the highest dose of KW-2450 in combination with lapatinib and letrozole that can be administered safely to subjects with advanced or metastatic breast cancer and to evaluate its effectiveness. This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- KW-2450 in combination with lapatinib and letrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 5 sitesUnited States
- Study dates
- Dec 2010to Dec 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histopathologically or cytologically confirmed, advanced or metastatic breast cancer (stage IIIb, IIIc or IV disease) including inflammatory breast cancer or inoperable locally advanced disease.
- Documented ErbB2 overexpression
- Estrogen receptor positive (ER+) and/or progesterone positive (PgR+) tumors
- Measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria
- A life expectancy of > 3 months for Phase 1 and > 6 months for Phase 2
- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry in Phase 1 and ≤ 1 in Phase 2;
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- Normal cardiac ejection fraction
- Adequate hematologic, hepatic and renal function
- Post-menopausal female (defined as the absence of a menstrual cycle for at least 12 consecutive months) or male subjects ≥ 18 years of age.
- Sign an IRB or EC approved informed consent
Who cannot join
- Type 1 diabetes or uncontrolled Type 2 diabetes
- Subjects showing clinical evidence or with a history of cataract(s), proliferate retinopathy or significant macular edema
- Subjects with abnormal free T4 values and a history or evidence of thyroid disease
- Subjects who are unable or unwilling to take metformin
- Uncontrolled intercurrent illness
- Known or suspected human immunodeficiency virus (HIV) infection or hepatitis B or C
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- Subjects with inflammatory diseases of the gastrointestinal tract
- History of other malignancy. Subjects who have been disease free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
- Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor
- A history of prior treatment with other agents specifically targeting IGFRs
- Subjects who require pharmacological doses of glucocorticoids beyond replacement doses. The use of topical, intra-ocular or inhalation glucocorticoids is permitted
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Sylvester Comprehensive Cancer Center
Deerfield Beach, Florida, 33136
Clinical Oncology Associates
Farmington Hills, Michigan, 48336
MD Anderson Cancer Center
Houston, Texas, 77030
Breastlink Research Group
Long Beach, California, 90250
Associates in Hematology-Oncology
Los Angeles, California, 90057
About this study
Official title: A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of KW-2450 in Combination With Lapatinib and Letrozole in Subjects With Advanced or Metastatic Breast Cancer Whose Tumors Overexpress HER2
This study will determine the highest dose of KW-2450 in combination with lapatinib and letrozole that can be administered safely to subjects with advanced or metastatic breast cancer and to evaluate its effectiveness.
This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study.
Read the detailed description
This open-label, sequential, ascending, multi-dose, Phase 1/2 study will enroll up to 198 post-menopausal subjects with advanced or metastatic breast cancer whose tumors overexpress HER2. Subjects at each dose level will receive KW-2450 orally, on a continuous daily schedule in combination with lapatinib and letrozole.
In the Phase 1 portion of the study, dose escalation may proceed once ≥ 3 subjects have completed Day 30. The safety of each dose level will be established prior to enrollment of subjects in the next dose level. Dose escalation will proceed sequentially. Up to 6 subjects may be enrolled at each dose level. Enrollment will proceed until the MTD has been established or the highest dose level has been reached.
The Phase 2 portion of the trial will enroll 168 additional subjects. The dose level will be based on overall safety and tolerability assessments from the Phase 1 portion of the study. The subjects will be randomized into two treatment arms (1) Arm A, KW-2450 plus lapatinib plus letrozole: (2) Arm B, lapatinib plus letrozole.
This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study.
- Conditions
- Breast Cancer
- Being tested
- KW-2450 in combination with lapatinib and letrozole
- Keywords
- advanced or 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.
KW-2450 in combination with lapatinib and letrozoleDrug
Also called KW-2450 lapatinib and letrozole
Three subjects will be assigned to each of 4 sequential cohorts. Dose escalation may proceed once at least 3 subjects have completed 30 days of study treatment. Subjects who withdraw prior to completing Day 30 for reasons other than DLT will be replaced. If a DLT is observed, additional subjects may be enrolled so that up to 6 subjects are enrolled at that dose level.
| Study group | Role | What they receive |
|---|---|---|
| Dose escallation | Experimental | Not described Receives: Drug: KW-2450 in combination with lapatinib and letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the safety, tolerability, and recommended Phase 2 dose of KW-2450 administered in combination with lapatinib and letrozole in subjects with previously treated or untreated advanced breast cancer.
Measured: 30 Days
Secondary outcomes (1)
To determine the PK profile of KW-2450, lapatinib, and letrozole when administered together
Measured: 1 year (or until PD)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2010 (estimated)
- Study startDec 2010
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: The results of the dose escalation phase did not identify a well-tolerated dose that would permit further study in Phase 2.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Hakko Kirin Pharma, Inc.
- Responsible party
- Sponsor
- Investigators
- Michael Kurman, MD, Study director, Kyowa Hakko Kirin Pharma, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01199367
- Sponsor's protocol ID
- 2450-US-002
- Status last verified
- Apr 2024
- First submitted
- 8 Sep 2010
- Last updated
- 25 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Dickson MA, P. LoRusso P, E. A. Sausville EA, Rao N, Kobayashi E, Kurman MR, Akinaga S, Schwartz GK. Open-label, sequential, ascending, multi-dose, phase I study of KW-2450 as monotherapy in subjects with previously treated advanced solid tumors. J Clin Oncol 29: 2011 (suppl; abstr 3078)
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of KW-2450 in Combination With Lapatinib and Letrozole in Subjects With Advanced or Metastatic Breast Cancer Whose Tumors Overexpress HER2
- ClinicalTrials.gov ID
- NCT01199367
- Acronym / sponsor ID
- 2450-US-002
- Conditions
- Breast Cancer
- Keywords
- advanced or metastatic breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The results of the dose escalation phase did not identify a well-tolerated dose that would permit further study in Phase 2.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Hakko Kirin Pharma, Inc.
- Study start
- Dec 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 10 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the highest dose of KW-2450 in combination with lapatinib and letrozole that can be administered safely to subjects with advanced or metastatic breast cancer and to evaluate its effectiveness.
This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study.
Detailed description
This open-label, sequential, ascending, multi-dose, Phase 1/2 study will enroll up to 198 post-menopausal subjects with advanced or metastatic breast cancer whose tumors overexpress HER2. Subjects at each dose level will receive KW-2450 orally, on a continuous daily schedule in combination with lapatinib and letrozole.
In the Phase 1 portion of the study, dose escalation may proceed once ≥ 3 subjects have completed Day 30. The safety of each dose level will be established prior to enrollment of subjects in the next dose level. Dose escalation will proceed sequentially. Up to 6 subjects may be enrolled at each dose level. Enrollment will proceed until the MTD has been established or the highest dose level has been reached.
The Phase 2 portion of the trial will enroll 168 additional subjects. The dose level will be based on overall safety and tolerability assessments from the Phase 1 portion of the study. The subjects will be randomized into two treatment arms (1) Arm A, KW-2450 plus lapatinib plus letrozole: (2) Arm B, lapatinib plus letrozole.
This study was terminated in Phase 1 and never proceeded to the Phase 2 portion of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose escallation | Experimental | Drug: KW-2450 in combination with lapatinib and letrozole |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histopathologically or cytologically confirmed, advanced or metastatic breast cancer (stage IIIb, IIIc or IV disease) including inflammatory breast cancer or inoperable locally advanced disease.
- Documented ErbB2 overexpression
- Estrogen receptor positive (ER+) and/or progesterone positive (PgR+) tumors
- Measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria
- A life expectancy of > 3 months for Phase 1 and > 6 months for Phase 2
Key exclusion criteria (11 listed)
- Type 1 diabetes or uncontrolled Type 2 diabetes
- Subjects showing clinical evidence or with a history of cataract(s), proliferate retinopathy or significant macular edema
- Subjects with abnormal free T4 values and a history or evidence of thyroid disease
- Subjects who are unable or unwilling to take metformin
- Uncontrolled intercurrent illness
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 |
|---|---|---|
| KW-2450 in combination with lapatinib and letrozoleAlso: KW-2450 lapatinib and letrozoleThree subjects will be assigned to each of 4 sequential cohorts. Dose escalation may proceed once at least 3 subjects have completed 30 days of study treatment. Subjects who withdraw prior to completing Day 30 for reasons other than DLT will be replaced. If a DLT is observed, additional subjects may be enrolled so that up to 6 subjects are enrolled at that dose level. | Drug | Dose escallation |
Primary outcome
To establish the safety, tolerability, and recommended Phase 2 dose of KW-2450 administered in combination with lapatinib and letrozole in subjects with previously treated or untreated advanced breast cancer.
Time frame: 30 Days
1 secondary outcome
To determine the PK profile of KW-2450, lapatinib, and letrozole when administered together
Time frame: 1 year (or until PD)
Results and safety
The study was stopped early (reason given: The results of the dose escalation phase did not identify a well-tolerated dose that would permit further study in Phase 2.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Results publicationDickson MA, P. LoRusso P, E. A. Sausville EA, Rao N, Kobayashi E, Kurman MR, Akinaga S, Schwartz GK. Open-label, sequential, ascending, multi-dose, phase I study of KW-2450 as monotherapy in subjects with previously treated advanced solid tumors. J Clin Oncol 29: 2011 (suppl; abstr 3078)
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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.
Michael Kurman, MD study director
Kyowa Hakko Kirin Pharma, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KW-2450 in combination with lapatinib and letrozole in people with Breast Cancer, run by Kyowa Kirin Co., Ltd. at 5 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 11 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: stopped early, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The results of the dose escalation phase did not identify a well-tolerated dose that would permit further study in Phase 2.). Results are not available in the source record.
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?
To establish the safety, tolerability, and recommended Phase 2 dose of KW-2450 administered in combination with lapatinib and letrozole in subjects with previously treated or untreated advanced breast cancer. (time frame: 30 Days). 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 NCT01199367, which also lists 1 linked publication.
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 25 Apr 2024.