Breast CancerPhase 1NCT01320592
PD0332991/Paclitaxel in Advanced Breast Cancer
A Phase 1 study testing PD0332991 and Paclitaxel in people with Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
This study is a phase I, single arm, open-label trial of PD0332991 in combination with Paclitaxel in patients with Rb-expressing metastatic breast cancer. Up to 20 patients are anticipated to be enrolled to reach the Maximum Tolerated Dose (MTD) of PD0332991 in combination with Paclitaxel. 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?
- PD0332991 and Paclitaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to May 2019
- 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
- Patient must have histologically or cytologically-confirmed metastatic breast cancer. Any ER, PR or Her2 status is allowed.
- Tumor must express Retinoblastoma (Rb) protein, as defined as any measureable staining by immunohistochemistry
- Male or female and > 18 years of age on the day of signing informed consent.
- Patient must have received < prior cytotoxic regimens for metastatic breast cancer. This does not include cytoxic regimens used in the adjuvant setting.
- Performance status of 0-1 on the Eastern Cooperative Oncology Group Performance Scale and life expectancy > 3 months.
- patient on the dose-escalation portion of the trial must have evaluable disease, defined as either measurable (by RECIST) or non-measurable disease (e.g. bone mets, pleural effusion or lymphangitic spread). Measurable disease is required for patients in the expanded RP2D cohort.
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- The subject must have adequate organ function, defined as follows:
- Bilirubin < 1.5 x upper normal limit or calculated creatinine clearance > 60 mL/min, and for subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper normal limit
- For subjects without extensive bone metastases: alkaline phosphatase levels < 2.5 x upper normal limit .
- For subjects with extensive bone metastases: alkaline phosphatase levels < 5 x upper normal limit .
- The subject must have adequate marrow function, defined as follows
- Absolute neutrophil count (ANC) >1500/mm
- Platelets > 100,000/mm
- Hemoglobin > 9 g/dL
- Female patient of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication and agree to the use of effective methods of contraception while on study.
- Patient must be capable of, and must voluntarily agree to participate by giving written informed consent.
- Patient must be able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.
- Prior taxane therapy in the adjuvant or metastatic setting is allowed.
- Concomitant use of biphosphonates is allowed.
- Patients with stable, treated CNS disease are eligible.
Who cannot join
- Patient who has had chemotherapy, radiotherapy or hormonal therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be < Grade 1.
- patients less than 4 weeks post major surgical procedure (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia.
- Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. Oral corticosteroids for control of CNS symptoms are allowed.
- Patient has known hypersensitivity to the components of study drug or its analogs.
- The subject has uncontrolled intercurrent illness including, but not limited to Ongoing or active infection
- Diabetes mellitus
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- Hypertension
- Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months.
- Patient has baseline neuropathy of > grade 2
- Patients who have known allergic reactions to Paclitaxel or IV Contrast Dye despite standard prophylaxis.
- The subject is pregnant or breastfeeding
- The subject is known to be positive for the human immunodeficiency virus (HIV). Note: baseline HIV screening is not required.
- The subject is unable eor unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase 1 Trial of PD0332991 and Paclitaxel in Patients With Rb-Expressing Advanced Breast Cancer
This study is a phase I, single arm, open-label trial of PD0332991 in combination with Paclitaxel in patients with Rb-expressing metastatic breast cancer. Up to 20 patients are anticipated to be enrolled to reach the Maximum Tolerated Dose (MTD) of PD0332991 in combination with Paclitaxel. Once the MTD is established, an additional expanded cohort of 10 patients will be enrolled at that dose to establish the Recommended Phase 2 Dose (RP2D), obtain additional safety data and perform exploratory biomarker studies.
Read the detailed description
This study is a phase I, single arm, open-label trial of PD0332991 in combination with paclitaxel in patients with Rb-expressing metastatic breast cancer. Patients will be treated as shown in the schema below. Up to 20 patients are anticipated to be enrolled to reach the MTD of PD0332991 in combination with Paclitaxel. Once the MTD is established, an additional expanded cohort of 10 patients will be enrolled at that dose to establish the RP2D, obtain additional safety data and perform exploratory biomarker studies. The primary endpoint will be assessed after one cycle of therapy. Patients will remain on study until dose limiting toxicity, disease progression or physician/patient discretion. Safety assessment will continue for the duration of patient participation.
- Conditions
- Breast Cancer
- Being tested
- PD0332991, Paclitaxel
- Keywords
- Patient must have histologically or cytologically-confirmed metastatic, breast cancer, Any ER, PR or Her2 status is allowed., Tumor must express Retinoblastoma (Rb) protein, defined as, any measurable staining by immunohistochemistry on the invasive tumor component, <3 prior cytoxic chemotherapy regimens for metastatic disease., Performance status of 0-1 on the Eastern Cooperative Oncology Group Performance Scale and life expectancy > 3 months., Patient must have evaluable disease. Measureable disease is not required., The subject has adequate organ function
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD0332991Drug
PaclitaxelDrug
| Study group | Role | What they receive |
|---|---|---|
| PD0332991 and Paclitaxel | Experimental | PD0332991 in combination with weekly paclitaxel at a fixed dose of 80 mg/m2 Receives: Drug: PD0332991; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine the Adverse Events of PD0332991
To determine the maximally-tolerated dose and safety of PD0332991 in combination with a fixed, weekly dose of Paclitaxel of 80 mg/m2 and to characterize the safety of the combination during the first three cycles of therapy.
Measured: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days) .
Secondary outcomes (2)
Maximally Tolerated Dose in an expanded Cohort of Breast Cancer Patients
To explore the activity of the combination at the MTD in an expanded cohort of breast cancer patients.
Measured: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)
To explore the relationship between selected biomarkers and efficacy, tolerability and safety outcomes
To explore the relationship between selected biomarkers and efficacy, tolerability and safety outcomes
Measured: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionMay 2019
- Study completionMay 2019
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.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- 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
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01320592
- Sponsor's protocol ID
- UPCC 02111
- Status last verified
- Apr 2020
- First submitted
- 16 Mar 2011
- Last updated
- 8 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Clark AS, McAndrew NP, Troxel A, Feldman M, Lal P, Rosen M, Burrell J, Redlinger C, Gallagher M, Bradbury AR, Domchek SM, Fox KR, O'Dwyer PJ, DeMichele AM. Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer. Clin Cancer Res. 2019 Apr 1;25(7):2072-2079. doi: 10.1158/1078-0432.CCR-18-0790. Epub 2019 Jan 11.
PubMed 30635336
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of PD0332991 and Paclitaxel in Patients With Rb-Expressing Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT01320592
- Acronym / sponsor ID
- UPCC 02111
- Conditions
- Breast Cancer
- Keywords
- Patient must have histologically or cytologically-confirmed metastatic, breast cancer, Any ER, PR or Her2 status is allowed., Tumor must express Retinoblastoma (Rb) protein, defined as, any measurable staining by immunohistochemistry on the invasive tumor component, <3 prior cytoxic chemotherapy regimens for metastatic disease., Performance status of 0-1 on the Eastern Cooperative Oncology Group Performance Scale and life expectancy > 3 months., Patient must have evaluable disease. Measureable disease is not required.
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Mar 2011 (actual)
- Primary completion
- May 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 22 Mar 2011 (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 is a phase I, single arm, open-label trial of PD0332991 in combination with Paclitaxel in patients with Rb-expressing metastatic breast cancer. Up to 20 patients are anticipated to be enrolled to reach the Maximum Tolerated Dose (MTD) of PD0332991 in combination with Paclitaxel. Once the MTD is established, an additional expanded cohort of 10 patients will be enrolled at that dose to establish the Recommended Phase 2 Dose (RP2D), obtain additional safety data and perform exploratory biomarker studies.
Detailed description
This study is a phase I, single arm, open-label trial of PD0332991 in combination with paclitaxel in patients with Rb-expressing metastatic breast cancer. Patients will be treated as shown in the schema below. Up to 20 patients are anticipated to be enrolled to reach the MTD of PD0332991 in combination with Paclitaxel. Once the MTD is established, an additional expanded cohort of 10 patients will be enrolled at that dose to establish the RP2D, obtain additional safety data and perform exploratory biomarker studies. The primary endpoint will be assessed after one cycle of therapy. Patients will remain on study until dose limiting toxicity, disease progression or physician/patient discretion. Safety assessment will continue for the duration of patient participation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PD0332991 and Paclitaxel | Experimental | Drug: PD0332991, Drug: PaclitaxelPD0332991 in combination with weekly paclitaxel at a fixed dose of 80 mg/m2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patient must have histologically or cytologically-confirmed metastatic breast cancer. Any ER, PR or Her2 status is allowed.
- Tumor must express Retinoblastoma (Rb) protein, as defined as any measureable staining by immunohistochemistry
- Male or female and > 18 years of age on the day of signing informed consent.
- Patient must have received < prior cytotoxic regimens for metastatic breast cancer. This does not include cytoxic regimens used in the adjuvant setting.
- Performance status of 0-1 on the Eastern Cooperative Oncology Group Performance Scale and life expectancy > 3 months.
Key exclusion criteria (13 listed)
- Patient who has had chemotherapy, radiotherapy or hormonal therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be < Grade 1.
- patients less than 4 weeks post major surgical procedure (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia.
- Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. Oral corticosteroids for control of CNS symptoms are allowed.
- Patient has known hypersensitivity to the components of study drug or its analogs.
- The subject has uncontrolled intercurrent illness including, but not limited to Ongoing or active infection
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 |
|---|---|---|
| PD0332991 | Drug | PD0332991 and Paclitaxel |
| Paclitaxel | Drug | PD0332991 and Paclitaxel |
Primary outcome
To Determine the Adverse Events of PD0332991
Time frame: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days) .
To determine the maximally-tolerated dose and safety of PD0332991 in combination with a fixed, weekly dose of Paclitaxel of 80 mg/m2 and to characterize the safety of the combination during the first three cycles of therapy.
2 secondary outcomes
Maximally Tolerated Dose in an expanded Cohort of Breast Cancer Patients
Time frame: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)
To explore the relationship between selected biomarkers and efficacy, tolerability and safety outcomes
Time frame: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
- Derived from this study: PubMed 30635336Clark AS, McAndrew NP, Troxel A, Feldman M, Lal P, Rosen M, Burrell J, Redlinger C, Gallagher M, Bradbury AR, Domchek SM, Fox KR, O'Dwyer PJ, DeMichele AM. Combination Paclitaxel and Palbociclib: Results of a Phase I Trial in Advanced Breast Cancer. Clin Cancer Res. 2019 Apr 1;25(7):2072-2079. doi: 10.1158/1078-0432.CCR-18-0790. Epub 2019 Jan 11.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PD0332991 and Paclitaxel in people with Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site 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 20 inclusion and 13 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 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Determine the Adverse Events of PD0332991 (time frame: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 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 NCT01320592, 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 8 Apr 2020.