A Clinical Research Study to Determine Whether PD 0332991 May Be Effective in Treating Patients With Liver Cancer

NCT01356628 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 11D.14JT 1848
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2 Study of PD-0332991 in the treatment of patients with Advanced Hepatocellular Carcinoma (HCC), a type of adenocarcinoma and the most common type of liver tumor. PD-0332991 is a compound that stops the tumor cell from entering the Synthesis phase of the cell cycle, therefore stopping DNA multiplication and decreased tumor cell copying.

Conditions

Advanced Hepatocellular Carcinoma; HCC; Liver Cancer

Keywords

Advanced Hepatocellular Carcinoma; HCC; Liver Cancer; PD-0332991

Outcome Measures

Primary Outcomes (1)

• Time to Disease Progression

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST Version 1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (3)

• Number of Adverse Events

  From date of randomization through study completion, assessed up to 100 months

• Overall Survival (OS)

  Every 2 weeks during first 3 cycles, then monthly during treatment. Then Day 28, Day 56 and every 3 months from last administration of protocol directed therapy or death

• Response Rate (RR)

  Every 8 weeks

Study Arms (1)

PD-0332991

EXPERIMENTAL

PD-0332991 in the Treatment in Patients with Advanced Hepatocellular Carcinoma

Drug: PD-0332991

Interventions

PD-0332991 DRUG

PD-0332991, 125mg, 3 cycles

PD-0332991

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age \> or = 18 years with HCC refractory to currently available therapies.
• Documented HCC by at least 2 out of 3 mentioned criteria and evidence of non-resectability by a multidisciplinary team:
• A. Radiological - MRI with arterial enhancement and rapid venous washout B. Biopsy C. Serum alpha-fetoprotein level \> or = 200
• Positive staining for RB-function on tumor biopsy.
• Subject must be able to give written informed consent and be able to follow protocol requirements
• Life expectancy greater than 3 months
• Be Child's-Pugh class A or B
• ECOG Performance status of \< or = 2
• If female of childbearing potential must have negative pregnancy test at screening and may not be breast-feeding
• Females of child-bearing potential (\< one year post-menopausal with documented FSH greater than 30 IU/L or surgically not sterile), must agree to practice an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device, condom, diaphragm with spermicidal, cervical cap, abstinence or sterile sex partner) from the time informed consent is signed through follow-up. Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up.
• No other active malignancy requiring treatment in the last 3 years other than adequately treated non-melanomatous skin cancer, adequately treated cervical carcinoma in-situ, superficial adequately treated bladder cancer or prostatic intraepithelial neoplasia without evidence of prostate cancer.
• Adequate bone marrow, liver and renal function as assessed by the following:
• A. Hemoglobin \> or = 8 g/dL B. WBC \> or = 4,000/uL C. Absolute neutrophil count \> or = 1,500/uL D. Platelets \> or = 75,000/uL E. Total bilirubin \< or = 1.5 times ULN F. ALT and AST \< or = 5 times ULN G. Creatinine \< or = 1.5 times ULN H. Albumin \> or = 2.5 mg/dL
• Subjects who have received previous radiotherapy, loco-regional, or systemic therapy are eligible. A minimum interval of 4 weeks since the last anti-cancer treatment of any kind is required.
• Subjects with brain metastases or a history of previously treated brain metastasis are eligible but must:

You may not qualify if:

• Any concurrent active malignancy requiring treatment (other than basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder tumors, or other malignancies curatively treated \> 3 years prior to study entry)
• History of severe cardiovascular disease within the last 12 months: symptomatic congestive heart failure, myocardial infarction, coronary artery disease (CAD), life threatening arrhythmias, uncontrolled hypertension
• Renal failure requiring hemo- or peritoneal dialysis
• Unstable systemic diseases or active uncontrolled infection
• Known history of HIV infection
• Clinically significant gastrointestinal bleeding within 30 days prior to study entry
• Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to study entry
• Child's-Pugh Class C
• Any malabsorption problem that, in the investigator's opinion, would prevent adequate absorption of the study drug
• Presence of any other medical complications that in the investigator's opinion, suggests a survival of \< 3 months
• Substance abuse, or medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Patient inability to swallow oral medications
• Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
• Pregnant or breast-feeding patients
• Being of reproductive potential and unable or unwilling to practice an effective contraceptive method

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Pfizer: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (3)

• Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK, Toogood PL. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.

  PMID: 15542782 BACKGROUND

• Toogood PL, Harvey PJ, Repine JT, Sheehan DJ, VanderWel SN, Zhou H, Keller PR, McNamara DJ, Sherry D, Zhu T, Brodfuehrer J, Choi C, Barvian MR, Fry DW. Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6. J Med Chem. 2005 Apr 7;48(7):2388-406. doi: 10.1021/jm049354h.

  PMID: 15801831 BACKGROUND

• Rivadeneira DB, Mayhew CN, Thangavel C, Sotillo E, Reed CA, Grana X, Knudsen ES. Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells. Gastroenterology. 2010 May;138(5):1920-30. doi: 10.1053/j.gastro.2010.01.007. Epub 2010 Jan 25.

  PMID: 20100483 BACKGROUND

Related Links

• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Liver Neoplasms

Interventions

palbociclib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Dr. Avnish Bhatia
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University

avnish.Bhatia@jefferson.edu

215-955-8874

Study Officials

• Avnish Bhatia, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2011
• First Posted: May 19, 2011
• Study Start: May 25, 2011
• Primary Completion: June 1, 2023
• Study Completion: December 16, 2023
• Last Updated: July 28, 2025
• Results First Posted: January 5, 2018

Record last verified: 2025-07

Locations

US (1)