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Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Solid Tumor, Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Adult Central Nervous System Germ Cell Tumor, Adult Teratoma, Benign Teratoma, Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, Familial Testicular Germ Cell Tumor, HER2-negative Breast Cancer, HER2-positive Breast Cancer, Male Breast Cancer, Ovarian Immature Teratoma, Ovarian Mature Teratoma, Ovarian Monodermal and Highly Specialized Teratoma, Progesterone Receptor-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Recurrent Breast Cancer, Recurrent Colon Cancer, Recurrent Extragonadal Germ Cell Tumor, Recurrent Extragonadal Non-seminomatous Germ Cell Tumor, Recurrent Extragonadal Seminoma, Recurrent Malignant Testicular Germ Cell Tumor, Recurrent Melanoma, Recurrent Ovarian Germ Cell Tumor, Recurrent Rectal Cancer, Stage III Extragonadal Non-seminomatous Germ Cell Tumor, Stage III Extragonadal Seminoma, Stage III Malignant Testicular Germ Cell Tumor, Stage III Ovarian Germ Cell Tumor, Stage IV Breast Cancer, Stage IV Colon Cancer, Stage IV Extragonadal Non-seminomatous Germ Cell Tumor, Stage IV Extragonadal Seminoma, Stage IV Melanoma, Stage IV Ovarian Germ Cell Tumor, Stage IV Rectal Cancer, Testicular Immature Teratoma, Testicular Mature Teratoma

Thank you

Trial Information

Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer


PRIMARY OBJECTIVES:

I. 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.

II. To evaluate the safety and tolerability of PD 0332991 administered to subjects with
refractory solid tumors.

SECONDARY OBJECTIVES:

I. To assess the pharmacodynamic effects of PD0332991 on tumor and non-tumor tissue.

II. To investigate the relationship between selected biomarkers, PK and/or efficacy and
safety outcomes.

III. To estimate the population pharmacokinetic for PD 0332991 and to correlate PK with
efficacy outcomes.

IV: To perform a Phase II evaluation of PD 0332991 in a population defined as potential
responders on the basis of CCND1 gene amplification.

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.

Inclusion Criteria


Inclusion

- All subjects treated under this protocol will have histologically documented cancer
of one of the following types:

- Metastatic breast cancer with: I. Histologically confirmed invasive carcinoma of the
breast; tumors with any ER,PR and Her2/neu status are eligible; II. Evidence of
metastatic (stage IV) breast cancer, with at least one measurable lesion by RECIST
criteria

- Metastatic colorectal cancer: I. Histologically confirmed adenocarcinoma of the colon
or rectum; II. Evidence of local or distant progression, with at least one measurable
lesion by RECIST criteria

- Metastatic melanoma with CDK4 mutation or amplification

- Cisplatin-refractory, unresectable germ cell tumors

- The following tumor types if tissues tests positive for CCND1 amplification;
Esophageal cancer, especially squamous cell - cohorts to be analyzed separately, Head
and neck squamous cell cancer, Breast especially those with luminal B expression
profile, ER positively, and high Ki67 expression. (in addition to breast cancer
patients above)., Liposarcoma, Any histology if already known to carry the
amplification.

- The subject has disease that is assessable by tumor marker, physical, or radiologic
means

- ECOG performance status of 0 or 1

- Bilirubin =< 1.5 x the upper limit of normal (ULN)

- Serum creatinine =< 1.5 x UNL or calculated creatinine clearance >= 60 mL/min

- For subjects without liver metastases: alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) =< 2.5 x ULN

- For subjects with liver metastases: alanine aminotransferase (ALT) and aspartate
aminotransferase =< 5 x ULN

- For subjects without extensive bone metastases: alkaline phosphatase levels =< 2.5 x
ULN

- For subjects with extensive bone metastases: alkaline phosphatase levels =< 5 x ULN

- Absolute neutrophil count (ANC) >= 1500/mm^3

- Platelets >= 100,000/mm^3

- Hemoglobin > 9 g/dL

- All tumors must test positive for Rb expression

- 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

- 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

Exclusion

- 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

- The subject has received any other type of investigational agent on a protocol 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

- The subject has uncontrolled intercurrent illness including, but not limited to: I.
Ongoing or active infection; II. Diabetes mellitus; III. Hypertension; IV.
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

- If a subject requires additional anticancer treatment, he or she must be withdrawn
from the study (with the exception of palliative radiotherapy, which may be allowed
during the study with the approval of the sponsor)

- No concurrent investigational agents will be permitted

- No concurrent anticancer treatment will be permitted

- High dose (> 60mg/day) or chronic (> 3months) steroid use is not allowed during the
course of this study as it may interfere with metabolism of the study drug

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rates

Safety Issue:

No

Principal Investigator

Peter ODwyer

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania

Authority:

United States: Institutional Review Board

Study ID:

UPCC 03909

NCT ID:

NCT01037790

Start Date:

October 2009

Completion Date:

Related Keywords:

  • Adult Solid Tumor
  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum
  • Adult Central Nervous System Germ Cell Tumor
  • Adult Teratoma
  • Benign Teratoma
  • Estrogen Receptor-negative Breast Cancer
  • Estrogen Receptor-positive Breast Cancer
  • Familial Testicular Germ Cell Tumor
  • HER2-negative Breast Cancer
  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Ovarian Immature Teratoma
  • Ovarian Mature Teratoma
  • Ovarian Monodermal and Highly Specialized Teratoma
  • Progesterone Receptor-negative Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Recurrent Breast Cancer
  • Recurrent Colon Cancer
  • Recurrent Extragonadal Germ Cell Tumor
  • Recurrent Extragonadal Non-seminomatous Germ Cell Tumor
  • Recurrent Extragonadal Seminoma
  • Recurrent Malignant Testicular Germ Cell Tumor
  • Recurrent Melanoma
  • Recurrent Ovarian Germ Cell Tumor
  • Recurrent Rectal Cancer
  • Stage III Extragonadal Non-seminomatous Germ Cell Tumor
  • Stage III Extragonadal Seminoma
  • Stage III Malignant Testicular Germ Cell Tumor
  • Stage III Ovarian Germ Cell Tumor
  • Stage IV Breast Cancer
  • Stage IV Colon Cancer
  • Stage IV Extragonadal Non-seminomatous Germ Cell Tumor
  • Stage IV Extragonadal Seminoma
  • Stage IV Melanoma
  • Stage IV Ovarian Germ Cell Tumor
  • Stage IV Rectal Cancer
  • Testicular Immature Teratoma
  • Testicular Mature Teratoma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Breast Neoplasms
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Dermoid Cyst
  • Teratoma
  • Melanoma
  • Seminoma
  • Testicular Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Breast Neoplasms, Male
  • Germinoma
  • Ovarian Neoplasms

Name

Location

Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283