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:

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. Histology confirmed ovarian cancer serous or endometrioid high degree, fallopian tube
             or with locoregional recurrence peritoneum (not amenable to curative treatment) or
             metastatic;

          6. Estrogen (ER) and/or progesterone (RP) receptor positive tumor, defined as > 10% by
             immunohistochemical examination in the local laboratory;

          7. Availability of tumor sample from the primary tumor or metastasis, fixed in formalin
             and embedded in paraffin, for confirmation of positivity for ER and/or RP in a central
             laboratory;

          8. Disease measurable by RECIST 1.1 as assessed by the local investigator or radiologist;

          9. Patients must have chemotherapy application for recurrence locoregional or metastatic
             according to the following criteria:

               -  at least one platinum-based chemotherapy regimen;

               -  have confirmed no more than 3 chemotherapy regimens for locally advanced or
                  metastatic disease

         10. Patient must have radiographic disease progression to last treatment;

         11. Functional capacity by the Eastern Cooperative Oncology Group (ECOG) ≤ 2;

         12. Adequate bone marrow function:

               -  Absolute neutrophil count (CAN) ≥ 1,500/mm3 (≥ 1.5x109/L)

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

               -  Hemoglobin ≥ 9.0 g/dL;

        12. Adequate liver function:

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

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (≤ 5.0
             x ULN if liver tumor was involved)

          -  Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 x ULN if any liver tumor involvement); 13.
             Adequate kidney function:

          -  Estimated creatinine clearance ≥ 15 mL/min; 14. Evidence of lack of potential to
             become pregnant:

          -  Post-menopause (defined as at least 1 year without menstruation) before selection, or

          -  Radiotherapy-induced oophorectomy with the last menstruation > 1 year ago, or

          -  Surgical sterilization (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 CDK4/6 inhibitors or endocrine therapy;

          3. Disease progression during or within 6 months of the first platinum-based chemotherapy
             regimen.

          4. Persistent toxicities (Grade 2 or higher) caused by previous anticancer therapy
             (excluding alopecia);

          5. Patients with a second primary cancer, except: adequately treated non-melanoma skin
             cancer, cervical cancer in situ curatively treated, Ductal carcinoma in situ (DCIS),
             stage 1 grade 1 endometrial carcinoma curatively treated with no evidence of illness
             for 3 years;

          6. Last dose of chemotherapy or radiotherapy within 3 weeks of study enrollment;

          7. Patients with symptomatic uncontrolled brain metastases. An exam to confirm the
             absence of brain metastases is not necessary;

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

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

         10. Patients who have difficulty taking oral medication or any digestive tract dysfunction
             or inflammatory bowel disease that interferes with intestinal absorption of
             medications (eg, partial bowel obstruction or malabsorption);

         11. Patients received potent inhibitors or inducers of CYP3A4 within 7 days of
             randomization;

         12. Pregnant or nursing women;

         13. The patient has a known history of testing positive for human immunodeficiency virus
             (HIV);

         14. Patients with known liver disease (ie, Hepatitis B or C);

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

         16. Other acute or chronic medical or psychiatric condition or severe laboratory
             abnormality that could increase the risk associated with participation in the study or
             that could interfere with the interpretation of the study results and, in the
             investigator's judgment, would make the research participant unsuitable 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:Recruiting
Lead Sponsor:Latin American Cooperative Oncology Group

Trial Keywords

  • Palbociclib
  • Letrozole
  • Ovarian Cancer

Last Updated

August 19, 2021