Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian Cancer. (LACOG1018)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03936270
Recruitment Status : Recruiting
First Posted : May 3, 2019
Last Update Posted : August 30, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Latin American Cooperative Oncology Group

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Palbociclib 125mg Drug: Letrozole 2.5mg Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Palbociclib Plus Letrozole Treatment After Progression to Second Line Chemotherapy for Women With ER/PR-positive Ovarian Cancer.
Actual Study Start Date : January 27, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: Palbociclib 125mg + Letrozole 2.5mg
Palbociclib 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).
Drug: Palbociclib 125mg
The Palbociclib capsules supplied for this study contains 75 mg, 100 mg or 125 mg of Palbociclib. It must be taken orally 125 mg once daily for 21 consecutive days followed by 7 days off treatment (Schedule 3/1) to comprise a complete cycle of 28 days.
Other Name: Ibrance®

Drug: Letrozole 2.5mg
Letrozole will be supplied as a 2.5 mg film-coated tablet. It must be taken at the recommended dose of 2.5 mg once daily.
Other Name: Femara




Primary Outcome Measures :
  1. Twelve weeks of Progression Free Survival [ Time Frame: 12 weeks ]
    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 :
  1. Overall response [ Time Frame: 2 years ]
    defined as the proportion of patients who have a partial or complete response to therapy according to RECIST 1.1

  2. Overall Survival [ Time Frame: 2 years ]
    Overall Survival at year 1 and 2

  3. Clinical Benefit Rate [ Time Frame: 2 years ]
    defined as the proportion of patients who have achieved complete response, partial response and stable disease for at least 24 weeks.

  4. Duration of response [ Time Frame: 2 years ]
    defined as the time from response to progression by RECIST v11.1 or death

  5. CA-125 response (GCIG criteria) [ Time Frame: 2 years ]
    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)

  6. Time to progression by CA-125 (GCIG criteria) or RECIST [ Time Frame: 2 years ]
    defined as the time from response to progression by CA 125 (GCIG criteria) or RECIST

  7. Quality of Life (FACT-O questionnaire) [ Time Frame: 2 years ]
    assessed using the FACT-O questionnaire

  8. Safety (adverse events) [ Time Frame: 2 years ]
    defined as the proportion of patients who present adverse events



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03936270


Contacts
Layout table for location contacts
Contact: Laura Voelcker +55 51 3384 5334 laura.voelcker@lacogcancerresearch.org

Locations
Layout table for location information
Brazil
Universidade Federal de Minas Gerais Recruiting
Belo Horizonte, Minas Gerais, Brazil
Contact: Angelica Nogueira Rodrigues         
CPO Pucrs Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil
Contact: Fernanda Bronzon Damian         
Instituto Nacional do Câncer - INCA Recruiting
Rio De Janeiro, Brazil
Contact: Andréia Cristina Melo         
AC Camargo Cancer Center Suspended
São Paulo, Brazil
Hospital Beneficência Portuguesa Recruiting
São Paulo, Brazil
Contact: Graziela Zibetti Dal Molin         
Hospital Pérola Byington Not yet recruiting
São Paulo, Brazil
Contact: André Mattar         
Instituto do Câncer do Estado de São Paulo - ICESP Recruiting
São Paulo, Brazil
Contact: Elias Abdo Filho         
Sponsors and Collaborators
Latin American Cooperative Oncology Group
Pfizer
Investigators
Layout table for investigator information
Study Director: Gustavo Werutsky, MD Latin American Cooperative Oncology Group
Layout table for additonal information
Responsible Party: Latin American Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT03936270    
Other Study ID Numbers: LACOG 1018
First Posted: May 3, 2019    Key Record Dates
Last Update Posted: August 30, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Latin American Cooperative Oncology Group:
Palbociclib
Letrozole
Ovarian Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Letrozole
Palbociclib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors