Clinical Trials /

Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian Cancer.

NCT03936270

Description:

The primary objective of this study is to evaluate 12 weeks progression-free survival (PFS) rate of Palbociclib plus Letrozole in ER/PR positive endometrioid or high-grade serous ovarian cancer who have disease progression on second-line chemotherapy.

Related Conditions:
  • Malignant Ovarian Serous Tumor
  • Ovarian Endometrioid Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian Cancer.
  • Official Title: Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian Cancer.

Clinical Trial IDs

  • ORG STUDY ID: LACOG 1018
  • NCT ID: NCT03936270

Conditions

  • Ovarian Cancer

Interventions

DrugSynonymsArms
Palbociclib 125mgIbrance®Palbociclib 125mg + Letrozole 2.5mg
Letrozole 2.5mgFemaraPalbociclib 125mg + Letrozole 2.5mg

Purpose

The primary objective of this study is to evaluate 12 weeks progression-free survival (PFS) rate of Palbociclib plus Letrozole in ER/PR positive endometrioid or high-grade serous ovarian cancer who have disease progression on second-line chemotherapy.

Detailed Description

      Letrozole (Femara®) is an oral non-steroidal aromatase inhibitor that is approved worldwide
      for the treatment of postmenopausal women with breast cancer. It is administered orally on a
      continuous 2.5 mg daily dosing regimen and has a good toxicity profile. Palbociclib
      (Ibrance®) is an active potent and highly selective reversible inhibitor of cyclin- dependent
      kinases 4 and 6 (CDK4/6). Palbociclib was approved by the United States Food and Drug
      Administration (U.S. FDA) and the European Medicines Agency (EMA) for the treatment of
      postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor
      receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an
      aromatase inhibitor based on a randomized, double-blind, placebo-controlled, international
      clinical trial PALOMA-2. It is administered orally on a dose of 125 mg per day in 4-week
      cycles (3 weeks of treatment followed by 1 week off). This trial was based on preclinical
      studies that showed a synergistic effect between targeting the ER and cyclin-D-CDK4/6-Rb
      pathway. The principal toxicity was myelotoxicity but it was managed with appropriate
      supportive care and dose reductions13.

      Based on the results of phase 1 and 2 clinical trials of CDK4/6 inhibitors used as
      monotherapy to treat patients with recurrent ovarian cancer, we hypothesized that, as
      Palbociclibe is active in this population and many ovarian cancer show ER/PR expression, its
      combination with Letrozole can improve outcomes in ER/PR positive endometrioid or high-grade
      serous Ovarian Cancer who have disease progression on second-line chemotherapy, similar to
      what is seen in breast cancer studies.
    

Trial Arms

NameTypeDescriptionInterventions
Palbociclib 125mg + Letrozole 2.5mgExperimentalPalbociclib 125mg per day, administered orally in 4-week cycles (3 weeks of treatment followed by 1 week off) PLUS Letrozole 2.5mg per day administered orally (continuous treatment).
  • Palbociclib 125mg
  • Letrozole 2.5mg

Eligibility Criteria

        Inclusion Criteria:

          1. Evidence of a personally signed and dated informed consent document indicating that
             the subject has been informed of all pertinent aspects of the study;

          2. Subject is willing and able to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures;

          3. 18 years of age or older;

          4. Patient agrees not to participate in another interventional study while on treatment;

          5. Histologically diagnosed endometrioid or high-grade serous ovarian cancer, estrogen
             (ER) and/or progesterone (PR) receptor positive (defined as > 10% by
             immunohistochemistry);

          6. Patients must have completed 2 previous courses of chemotherapy:

               1. The penultimate regimen must be a platinum-based chemotherapy course prior to
                  enrolment on the study:

               2. For the last chemotherapy course prior to enrolment on the study:

                    -  There is no pre-specified regimen;

                    -  It may contain a Platinum salt or not (depending upon Platinum sensitivity),
                       at discretion of treating Physician;

                    -  Patients must have demonstrated disease progression by RECIST v1.1 to the
                       last treatment

                    -  Patients must be treated on the study within 8 weeks of completion of their
                       final dose of second line regimen;

          7. Formalin fixed, paraffin embedded tumor sample from the primary tumor must be
             available for central testing;

          8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;

          9. Adequate bone marrow function at screening:

               -  Absolute Neutrophil Count (ANC) ≥ 1,500/mm³ (≥ 1.5x109/L)

               -  Platelets ≥ 100,000/mm³ or ≥ 100 x 109/L

               -  Hemoglobin ≥ 9.0 g/dL;

         10. Adequate liver function at screening:

               -  Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤ 3.0 x ULN if Gilbert
                  Syndrome)

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
                  (≤ 5.0 x ULN if there is tumor involvement in the liver)

               -  Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 x ULN if there is tumor involvement in
                  the liver);

         11. Adequate renal function at screening:

             - Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50mL/min;

         12. Evidence of non-childbearing potential:

               -  Postmenopausal (defined as at least 1 year without any menses) prior to
                  screening, or

               -  Radiation-induced oophorectomy with last menses >1 year ago, or

               -  Surgical sterilisation (bilateral oophorectomy or hysterectomy).

        Exclusion Criteria:

          1. Patients with a known hypersensitivity to Palbociclib or Letrozole or any of the
             excipients of the product;

          2. Previous treatment with CDK inhibitors or endocrine therapy;

          3. Persistent toxicities (grade 2 or greater) caused by previous cancer therapy
             (excluding alopecia);

          4. Patients with second primary cancer, except: adequately treated non-melanoma skin
             cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ
             (DCIS), stage 1 grade 1 endometrial carcinoma curatively treated with no evidence of
             disease for 3 years;

          5. Patients receiving any chemotherapy, radiotherapy, within 3 weeks from the last dose
             prior to study entry;

          6. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence
             of brain metastases is not required;

          7. Major surgical procedure within 3 weeks prior to study randomization, or one is
             planned during the course of the study;

          8. Patients considered poor medical risk due to a serious, uncontrolled medical disorder,
             non-malignant systemic disease or active, uncontrolled infection. Examples include,
             but are not limited to, uncontrolled ventricular arrhythmia, recent (within 6 months)
             myocardial infarction, cerebrovascular accident, gastrointestinal bleeding, or any
             psychiatric disorder that prohibits obtaining informed consent;

          9. Patients that have difficulty taking oral medication or any digestive tract
             dysfunction or inflammatory bowel disease that would interfere with the intestinal
             absorption of drugs (eg, partial bowel obstruction or malabsorption);

         10. Patients have received potent inhibitors or inducers of CYP3A4 within 7 days prior to
             randomization;

         11. Pregnant or breast feeding women;

         12. Patient has a known history of positive test for human immunodeficiency virus (HIV);

         13. Patients with known hepatic disease (ie, Hepatitis B or C);

         14. Subjects who are investigational site staff members directly involved in the conduct
             of the trial and their family members, site staff members otherwise supervised by the
             Investigator, or subject who are Pfizer employees directly involved in the conduct of
             the trial;

         15. Treatment with any investigational product during the last 28 days;

         16. QTc > 480ms, QT syndrome, Brugada syndrome, history QTc prolongation or Torsade de
             Points;

         17. Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or may
             interfere with the interpretation of study results and, in the judgment of the
             investigator, would make the subject inappropriate for entry into this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Twelve weeks of Progression Free Survival
Time Frame:12 weeks
Safety Issue:
Description:The primary objective of this study is to evaluate 12 weeks progression-free survival (PFS) rate of Palbociclib plus Letrozole in ER/PR positive endometrioid or high-grade serous ovarian cancer who have disease progression on second-line chemotherapy.

Secondary Outcome Measures

Measure:Overall response
Time Frame:2 years
Safety Issue:
Description:defined as the proportion of patients who have a partial or complete response to therapy according to RECIST 1.1
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall Survival at year 1 and 2
Measure:Clinical Benefit Rate
Time Frame:2 years
Safety Issue:
Description:defined as the proportion of patients who have achieved complete response, partial response and stable disease for at least 24 weeks.
Measure:Duration of response
Time Frame:2 years
Safety Issue:
Description:defined as the time from response to progression by RECIST v11.1 or death
Measure:CA-125 response (GCIG criteria)
Time Frame:2 years
Safety Issue:
Description:defined as the proportion of patients who have achieved at least a 50% reduction in CA 125 levels from a pretreatment sample (must be confirmed and maintained for at least 28 days)
Measure:Time to progression by CA-125 (GCIG criteria) or RECIST
Time Frame:2 years
Safety Issue:
Description:defined as the time from response to progression by CA 125 (GCIG criteria) or RECIST
Measure:Quality of Life (FACT-O questionnaire)
Time Frame:2 years
Safety Issue:
Description:assessed using the FACT-O questionnaire
Measure:Safety (adverse events)
Time Frame:2 years
Safety Issue:
Description:defined as the proportion of patients who present adverse events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Latin American Cooperative Oncology Group

Trial Keywords

  • Palbociclib
  • Letrozole
  • Ovarian Cancer

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