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

NCT01356628

Last updated date
Study Location
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Advanced Hepatocellular Carcinoma, HCC, Liver Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Male or female, age > or = 18 years with HCC refractory to currently available therapies.

2. 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

3. Positive staining for RB-function on tumor biopsy.

4. Subject must be able to give written informed consent and be able to follow protocol requirements

5. Life expectancy greater than 3 months

6. Be Child's-Pugh class A or B

7. ECOG Performance status of < or = 2

8. If female of childbearing potential must have negative pregnancy test at screening and may not be breast-feeding

9. 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.

10. 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.

11. 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

12. 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.

13. Subjects with brain metastases or a history of previously treated brain metastasis are eligible but must:

A. Have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior to enrollment B. AND have a baseline MRI or CT that shows no evidence of active intercranial disease C. AND be off steroids for at least 1 week prior to study enrollment

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. 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)


2. 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


3. Renal failure requiring hemo- or peritoneal dialysis


4. Unstable systemic diseases or active uncontrolled infection


5. Known history of HIV infection


6. Clinically significant gastrointestinal bleeding within 30 days prior to study entry


7. Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to
study entry


8. Child's-Pugh Class C


9. Any malabsorption problem that, in the investigator's opinion, would prevent adequate
absorption of the study drug


10. Presence of any other medical complications that in the investigator's opinion,
suggests a survival of < 3 months


11. 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


12. Patient inability to swallow oral medications


13. Any condition that is unstable or which could jeopardize the safety of the patient and
his/her compliance in the study


14. Pregnant or breast-feeding patients


15. Being of reproductive potential and unable or unwilling to practice an effective
contraceptive method


16. Lack of positive staining for RB-function on tumor biopsy.

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Advanced Hepatocellular Carcinoma, HCC, Liver CancerA Clinical Research Study to Determine Whether PD 0332991 May Be Effective in Treating Patients With Liver Cancer
NCT01356628
  1. Philadelphia, Pennsylvania
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Clinical Research Study to Determine Whether PD 0332991 May Be Effective in Treating Patients With Liver Cancer
Official Title  ICMJE A Phase II Study of PD-0332991 in Adult Patients With Advanced Hepatocellular Carcinoma
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.
Detailed Description

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most frequent cause of cancer-related mortality. To date, surgical resection and liver transplantation are considered the main curative treatment options for HCC (El-Serag et al. 2006). However, the majority (~75%) of patients present with advanced tumor stage and poor liver function, rendering the patient ineligible for surgical interventions. Until the multikinase inhibitor sorafenib (Nexavar) was approved for the treatment of HCC in patients with unresectable disease (disease that can't be removed by surgery), there were no standard systemic therapies, as classical cell killing drugs (administered singularly or in combination) had not led to reproducible response rates or survival benefit. Despite this, response rates to sorafenib are low with overall benefits modest, and moreover the toxicity profile of the drug limits treatment for many patients. There is still a critical need for additional effective drugs to treat advanced HCC.

PD-0332991 is an orally available, selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6), a key regulator of cell growth. Pre-clinical data with PD-0332991 demonstrated potent target-specificity. PD-0332991 demonstrated significant inhibition of tumor cell growth in hepatoma cell lines, as well as animal and xenograft model systems, and was more effective than the currently approved drug, sorafenib in these systems. Initial clinical trials have demonstrated and acceptable toxicity profile for the drug. Thus, PD-0332991 represents an ideal candidate for the treatment of patients with advanced HCC.

This trial is an open-label non-randomized single-institution study for subjects with inoperable, recurrent/refractory, advanced hepatocellular carcinoma (HCC). Subjects must have failed or be intolerant of standard first line therapy, sorafenib (Nexavar®). Eligible subjects will receive 125 mg PD-0332991 capsules orally once daily, administered on days 1-21 of a 28-day cycle, in repeated cycles. The primary objective of the study is to assess the time to disease progression (TTP). Secondary objectives include assessment of safety and tolerability, and determination of overall survival (OS) and response rate (RR).

Subjects will be permitted to receive protocol directed therapy until disease progression as determined by modified RECIST (Response Evaluation Criteria in Solid Tumors) guidelines or clinical progression, unacceptable toxicity, withdrawal of consent or death. Tumor response assessment will be performed by the Investigator and will consist of evaluation by CT or MRI every 8 weeks. Subjects who discontinue therapy will still be followed for safety on Day 28 (± 3 days), Day 56 (± 3 days) and every 3 months thereafter from the last administration of protocol-directed therapy or until death.

Subjects will be continuously assessed for evidence of acute and cumulative toxicity. Vital signs, physical examinations, performance status, laboratory safety tests will be obtained and assessed prior to drug administration at regular intervals throughout the study. Toxicity will be evaluated every 2 weeks during the first 3 cycles and thereafter monthly (once per cycle) by the Investigator according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Hepatocellular Carcinoma
  • HCC
  • Liver Cancer
Intervention  ICMJE Drug: PD-0332991
PD-0332991, 125mg, 3 cycles
Study Arms  ICMJE Experimental: PD-0332991
PD-0332991 in the Treatment in Patients with Advanced Hepatocellular Carcinoma
Intervention: Drug: PD-0332991
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 7, 2017)
23
Original Estimated Enrollment  ICMJE
 (submitted: May 17, 2011)
19
Estimated Study Completion Date  ICMJE August 2021
Actual Primary Completion Date April 9, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female, age > or = 18 years with HCC refractory to currently available therapies.
  2. 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

  3. Positive staining for RB-function on tumor biopsy.
  4. Subject must be able to give written informed consent and be able to follow protocol requirements
  5. Life expectancy greater than 3 months
  6. Be Child's-Pugh class A or B
  7. ECOG Performance status of < or = 2
  8. If female of childbearing potential must have negative pregnancy test at screening and may not be breast-feeding
  9. 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.
  10. 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.
  11. 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

  12. 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.
  13. Subjects with brain metastases or a history of previously treated brain metastasis are eligible but must:

A. Have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior to enrollment B. AND have a baseline MRI or CT that shows no evidence of active intercranial disease C. AND be off steroids for at least 1 week prior to study enrollment

Exclusion Criteria:

  1. 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)
  2. 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
  3. Renal failure requiring hemo- or peritoneal dialysis
  4. Unstable systemic diseases or active uncontrolled infection
  5. Known history of HIV infection
  6. Clinically significant gastrointestinal bleeding within 30 days prior to study entry
  7. Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to study entry
  8. Child's-Pugh Class C
  9. Any malabsorption problem that, in the investigator's opinion, would prevent adequate absorption of the study drug
  10. Presence of any other medical complications that in the investigator's opinion, suggests a survival of < 3 months
  11. 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
  12. Patient inability to swallow oral medications
  13. Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
  14. Pregnant or breast-feeding patients
  15. Being of reproductive potential and unable or unwilling to practice an effective contraceptive method
  16. Lack of positive staining for RB-function on tumor biopsy.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01356628
Other Study ID Numbers  ICMJE 11D.14
2010-41 ( Other Identifier: CCRRC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
Study Sponsor  ICMJE Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Avnish Bhatia, MDSidney Kimmel Cancer Center at Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP