Adult Solid TumorPhase 2NCT01037790
Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer
A Phase 2 study testing PD-0332991 in people with Adult Solid Tumor and Adenocarcinoma of the Colon, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
RATIONALE: PD 0332991 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and how well PD 0332991 works in treating patients with refractory solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Solid Tumor, Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum
- What is being tested?
- PD-0332991
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Oct 2019
- Phase
- Phase 2
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
- Disease Characteristics:
- All Subjects: All subjects treated under this protocol will have histologically documented cancer of one of the following types:
- Metastatic breast cancer (7 triple negative, 23 ER+ after the first 15 patients are enrolled on the non-CCND1cohort; in addition 10 HER2+ for combination trastuzumab and PD0332991 therapy) up to 55 total enrollment slots B. Metastatic colorectal cancer that harbors the Kras or BRAF mutation (15-30 enrollment slots) C. Advanced or metastatic esophageal and/or gastric cancer (15-30 enrollment slots) D. Cisplatin-refractory, unresectable germ cell tumors (15-30 enrollment slots) E. Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation, CCND2 amplification OR any other functional alteration at the G1/S checkpoint. (15-30 enrollment slots)
- Biopsy Requirements: For Subjects with accessible disease amenable to biopsy: A biopsy will be obtained pre-treatment and in during cycle 1 (while patient is receiving drug) for molecular markers of the cell cycle, and its inhibition.
- Subjects will be > 18 years old
- The subject has disease that is assessable by tumor marker, physical, or radiologic means.
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- The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- The subject has adequate organ function, defined as follows A. Bilirubin ≤ 1.5 x the upper limit of normal (ULN) B. Serum creatinine ≤ 1.5 x UNL or calculated creatinine clearance ≥ 60 mL/min, and C. For subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN D. For subjects with liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase ≤ 5 x ULN
- All tumors must test positive for Rb expression except:
- ER positive metastatic breast tumors (data now shows all to be Rb positive.) B. Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation, CCND2 amplification OR any other functional alteration at the G1/S checkpoint.
- The subject has adequate marrow function, defined as follows: A. Absolute neutrophil count (ANC) >1500/mm3 B. Platelets >100,000/mm3, and C. Hemoglobin > 9 g/dL
- The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
- Sexually active subjects (male and female) must use accepted methods of contraception during the course of the study and for 3 months after the last dose of protocol drug(s).
- Female subjects of childbearing potential must have a negative pregnancy test at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months.
- However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, or ovarian suppression.
Who cannot join
- The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of PD 0332991. . Patients with HER2-overexpressing tumors may receive trastuzumab up to the date of starting therapy, and may continue to receive trastuzumab while receiving PD0332991.
- The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
- The subject has not recovered from clinically-meaningful toxicity due to prior therapy (i.e., back to baseline or Grade ≤ 1), with the exception of neurotoxicity and alopecia.
- The subject has untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease unless the subject has a teratoma in which case s/he may be eligible if all other eligibility criteria are met
- The subject has uncontrolled intercurrent illness including, but not limited to:
- ongoing or active infection
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- diabetes mellitus
- hypertension
- symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
- The subject has a baseline corrected QT interval (QTc) > 470 ms.
- 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 or 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
RATIONALE: PD 0332991 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying the side effects and how well PD 0332991 works in treating patients with refractory solid tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the response rates following treatment with PD 0332991 in the following malignancies: 1) Metastatic breast cancer, 2) Metastatic colorectal cancer, 3) Metastatic melanoma with CDK4 mutation or amplification, or 4) Cisplatin-refractory, unresectable germ cell tumors.
OUTLINE:
Patients receive oral PD 0332991 once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of unacceptable toxicity or disease progression.
- Conditions
- Adult Solid Tumor, Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Adult Central Nervous System Germ Cell Tumor, Adult Teratoma, Benign Teratoma
- Being tested
- PD-0332991
- Medical subject headings
- Colonic Neoplasms, Rectal Neoplasms, Teratoma, Breast Neoplasms, Male, Breast Neoplasms, Testicular Neoplasms, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-0332991Drug
Also called Palbociclib
Given orally, 125 mg QD on a 21-day
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - Metastatic breast cancer | Experimental | Metastatic breast cancer
PD-0332991 Given orally, 125 mg QD on a 21-day Receives: Drug: PD-0332991 |
| Arm 2 - Metastatic colorectal cancer that harbors the Kras or BRAF mutation | Experimental | Metastatic colorectal cancer that harbors the Kras or BRAF mutation
PD-0332991 Given orally, 125 mg QD on a 21-day Receives: Drug: PD-0332991 |
| Arm 3 - Advanced or metastatic esophageal and/or gastric cancer | Experimental | Advanced or metastatic esophageal and/or gastric cancer
PD-0332991 Given orally, 125 mg QD on a 21-day Receives: Drug: PD-0332991 |
| Arm 4 - Cisplatin-refractory, unresectable germ cell tumors | Experimental | Cisplatin-refractory, unresectable germ cell tumors
PD-0332991 Given orally, 125 mg QD on a 21-day Receives: Drug: PD-0332991 |
| Arm 5 - CCND1amplification, CDK4/6mutation, CCND2amplification, OR other functional G1/S alterations | Experimental | Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation , CCND2 amplification OR any other functional alteration at the G1/S checkpoint.
PD-0332991 Given orally, 125 mg QD on a 21-day Receives: Drug: PD-0332991 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rates
Response rates will be measured using the Response Evaluation Criteria in Solid Tumors (RECIST):
Complete Response (CR) - Disappearance of all target lesions Partial Response (PR) - ≥30% decrease in the sum of the longest diameter of the target lesions compared with baseline Progressive Disease (PD) - ≥20% increase in the sum of the longest diameter of the target lesions compared with the smallest sum of the longest diameter recorded since treatment started OR The appearance of 1 or more new lesions Stable Disease (SD) - Neither PR or PD Not Evaluable (NE)
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2009 (estimated)
- Study startOct 2009
- Primary completionOct 2019
- Study completionOct 2019
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Adult Solid TumorStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter ODwyer, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01037790
- Sponsor's protocol ID
- UPCC 03909
- Status last verified
- Feb 2021
- First submitted
- 10 Dec 2009
- Last updated
- 11 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Karasic TB, O'Hara MH, Teitelbaum UR, Damjanov N, Giantonio BJ, d'Entremont TS, Gallagher M, Zhang PJ, O'Dwyer PJ. Phase II Trial of Palbociclib in Patients with Advanced Esophageal or Gastric Cancer. Oncologist. 2020 Dec;25(12):e1864-e1868. doi: 10.1634/theoncologist.2020-0681. Epub 2020 Aug 8.
PubMed 32692450McAndrew NP, Dickson MA, Clark AS, Troxel AB, O'Hara MH, Colameco C, Gallager M, Gramlich K, Zafman K, Vaughn D, Schwartz GK, O'Dwyer PJ, DeMichele A. Early treatment-related neutropenia predicts response to palbociclib. Br J Cancer. 2020 Sep;123(6):912-918. doi: 10.1038/s41416-020-0967-7. Epub 2020 Jul 9.
PubMed 32641862