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A Open Label Study of the Efficacy and Safety of PD0332991 a Selective Inhibitor of the Cyclin Dependent Kinases 4 and 6 in Patients With Recurrent Ovarian Cancer Demonstrating Rb-proficiency and Low p16 Expression

NCT01536743

Description:

The purpose of this study is to obtain an estimate of the biochemical response rate as determined by CA125 response using the Gynecologic Cancer Intergroup (GCIG) response criteria of PD0332991 in patients with recurrent ovarian epithelial carcinoma. CA125 response is defined as ≥ 50% decrease from the baseline CA125 level and confirmed ≥ 21 days after initial evaluation (baseline is defined as the higher value of 2 pre-treatment CA125 assessments).

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Open Label Study of the Efficacy and Safety of PD0332991 a Selective Inhibitor of the Cyclin Dependent Kinases 4 and 6 in Patients With Recurrent Ovarian Cancer Demonstrating Rb-proficiency and Low p16 Expression
  • Official Title: A Open Label Phase II Study of the Efficacy and Safety of PD0332991 a Selective Inhibitor of the Cyclin Dependent Kinases 4 and 6 in Patients With Recurrent Ovarian Cancer Demonstrating Rb-proficiency and Low p16 Expression

Clinical Trial IDs

  • ORG STUDY ID: 11-003234
  • NCT ID: NCT01536743

Conditions

  • Ovarian Epithelial Carcinoma

Interventions

DrugSynonymsArms
PD0332991PD0332991

Purpose

The purpose of this study is to obtain an estimate of the biochemical response rate as determined by CA125 response using the Gynecologic Cancer Intergroup (GCIG) response criteria of PD0332991 in patients with recurrent ovarian epithelial carcinoma. CA125 response is defined as ≥ 50% decrease from the baseline CA125 level and confirmed ≥ 21 days after initial evaluation (baseline is defined as the higher value of 2 pre-treatment CA125 assessments).

Trial Arms

NameTypeDescriptionInterventions
PD0332991Experimental30 patients with recurrent ovarian epithelial carcinoma demonstrating Rb-proficiency and absent or low expression of p16 will be registered to receive PD0332991 once a day by mouth in the morning on an empty stomach. PD0332991 will be administered daily for 3 weeks followed by 1 week off treatment (28 day cycle).
  • PD0332991

Eligibility Criteria

        Inclusion Criteria

          1. Histologically-confirmed ovarian epithelial (including fallopian tube and primary
             peritoneal) carcinoma.

          2. 2. Baseline paraffin embedded tissue from the patient's primary diagnosis is requested
             before study enrolment and should be forwarded to the designated central laboratory
             where central assessment of Rb and p16 expression will be performed by using
             immunohistochemistry. In patients with measurable disease a tissue biopsy may be
             obtained by core biopsy and submitted to the designated central laboratory.

          3. GCIG-defined CA125 progression and absence of disease upon imaging or small-volume
             asymptomatic disease upon imaging and who have progressed following one, two or three
             lines of chemotherapy for recurrent disease.

          4. If patients have small-volume disease the current study will be restricted to patients
             with minimal ascites not causing abdominal distention/mesenteric thickening or not
             requiring paracentesis, or lesions ≤4 cm by spiral computed tomography [CT] or
             magnetic resonance imaging [MRI] at baseline.

          5. Two pretreatment CA125 values (documented on two occasions taken at least one week
             apart) must be at least twice the upper limit of normal, or twice the nadir value if
             pretreatment CA125 values never normalized.

          6. Patients with platinum-sensitive or platinum-resistant disease defined by recurrence
             or progression of disease > 6 months or ≤ than 6 months after completion of frontline
             platinum based chemotherapy.

          7. ECOG performance status ≤ 1 and patients are to be ≥21 years of age.

          8. Resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE v.3.0
             Grade ≤ 1 and to baseline laboratory values as defined in the inclusion criterion
             immediately below.

          9. Adequate organ and bone marrow function as evidenced by:

               -  hemoglobin ≥ 9.0 g/dL

               -  absolute neutrophil count ≥ 1.5 x 109/L

               -  platelet count ≥ 100 x 109/L

               -  Renal function, as follows:

               -  Serum creatinine ≤ 1.5 x the ULN or calculated creatinine clearance ≥ 40 mL/min

               -  AST and ALT ≤ 2.5 x ULN

               -  total bilirubin ≤ 1.5 x ULN unless increase is due to Gilbert's disease or
                  similar syndrome involving slow conjugation of bilirubin,

         10. Adequate coagulation parameters (within 21 days prior to registration), International
             Normalized Ratio (INR) ≤1.5; Activated ProThrombin Time (APTT) ≤ 1.5 x ULN.

         11. Patient must be willing and able to comply with scheduled visits, treatment plans,
             laboratory tests, and other study procedures.

         12. Informed consent must be obtained in writing for all patients prior to performing
             study/screening procedures and prior to registration into the study.

        Exclusion Criteria

        Patients presenting with any of the following will not be included in the study:

          1. More than 4 prior chemotherapy regimens in the treatment of ovarian cancer.

          2. Anticipation of immediate need for a major surgical procedure (e.g., impending bowel
             obstruction, gastrointestinal perforation) or radiation therapy during the trial.

          3. Diagnosis of any second malignancy within the last 5 years, except for adequately
             treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the
             cervix uteri or breast.

          4. Treatment with chemotherapy, radiotherapy, surgery, blood products, or an
             investigational agent within 3 weeks of trial enrolment.

          5. Any of the following within 6 months prior to trial registration: myocardial
             infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft,
             NYHA class III or IV congestive heart failure, cerebrovascular accident or transient
             ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic
             event. PD0332991 in Recurrent Ovarian Cancer

          6. History of brain metastases, spinal cord compression, or carcinomatous meningitis.

          7. Patient of child-bearing potential is evidently pregnant (eg, positive human chorionic
             gonadotropin test) or is breast feeding. A woman with child bearing potential is
             defined as not surgically sterile or being post-menopausal for less than 6 months.

          8. Patient of child-bearing potential is not willing to use adequate contraceptive
             precautions. Adequate effective method of contraception are those which result in low
             failure rates, less than 1% per year, such as non-hormonal IUD, condoms, sexual
             abstinence or vasectomised partner.

          9. Known active infection, or on antiretroviral therapy for HIV disease or positive test
             for chronic hepatitis B or C infection.

         10. Mental condition rendering the patient unable to understand the nature, scope, and
             possible consequences of the trial.

         11. Refusal or inability to give informed consent to participate in the trial.

         12. Corrected QT (QTc) interval >470 msec.

         13. If radiotherapy is required in a given patient, that patient should be withdrawn from
             the study.

         14. Current use or anticipated need for: Food or drugs that are known strong CYP3A4
             inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,
             posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir,
             ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone,
             diltiazem, and delavirdine.

         15. Other severe acute or chronic medical or psychiatric condition, or significant
             laboratory abnormality requiring further investigation that may cause undue risk for
             the patient's safety, inhibit protocol participation, or interfere with interpretation
             of trial results, and in the judgment of the investigator would make the patient
             inappropriate for entry into this trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Estimate biochemical response rate as determined by CA125 response using the Gynecologic Cancer Intergroup (GCIG) response criteria of PD0332991 in patients with recurrent ovarian epithelial carcinoma.
Time Frame:4 weeks
Safety Issue:
Description:CA125 response is defined as ≥ 50% decrease from the baseline CA125 level and confirmed ≥ 21 days after initial evaluation (baseline is defined as the higher value of 2 pre-treatment CA125 assessments).

Secondary Outcome Measures

Measure:Toxicity of PD0332991.
Time Frame:4 weeks
Safety Issue:
Description:Toxicity of PD0332991 will be graded using the NCI Common Toxicity Criteria, version 3.0
Measure:Assess health-related quality of life (HRQL),
Time Frame:4 weeks
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

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