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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/21/2021.

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

Clinicaltrials.gov identifier NCT03936270

Recruitment Status Recruiting

First Posted May 3, 2019

Last update posted June 16, 2020

Study Description

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:Ovarian Cancer
  • Intervention/Treatment: Drug: Palbociclib 125mg
    Drug: Letrozole 2.5mg
  • Phase: 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.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 39 participants
  • 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 2020
  • Estimated Primary Completion Date: April 2021
  • Estimated Study Completion Date: March 2023
Arms and interventions
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.

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.
Outcome Measures
  • 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
Eligibility Criteria
  • 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. 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.

Contacts and Locations
Contacts

Contact: Laura Voelcker +55 51 3384 5334 laura.voelcker@lacog.org.br

Locations

Brazil, Minas Gerais
Universidade Federal de Minas Gerais
Belo Horizonte

Brazil, Rio Grande Do Sul
CPO Pucrs
Porto Alegre

Brazil
Instituto Nacional do Câncer - INCA
Rio De Janeiro

Brazil
AC Camargo Cancer Center
São Paulo

Brazil
Hospital Beneficência Portuguesa
São Paulo

Brazil
Hospital Pérola Byington
São Paulo

Brazil
Instituto do Câncer do Estado de São Paulo - ICESP
São Paulo

Sponsors and Collaborators

Latin American Cooperative Oncology Group

Pfizer

Investigators

Study Director: Gustavo Werutsky, MD Latin American Cooperative Oncology Group

More Information
  • Responsible Party: Latin American Cooperative Oncology Group
  • ClinicalTrials.gov Identifier: NCT03936270 History of Changes
  • Other Study ID Numbers: LACOG 1018
  • First Posted: May 3, 2019 Key Record Dates
  • Last Update Posted: June 16, 2020
  • Last Verified: June 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Undecided
  • 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.: Yes
  • Keywords provided by Latin American Cooperative Oncology Group: Palbociclib
    Letrozole
    Ovarian Cancer
  • Additional relevant MeSH terms: Ovarian Neoplasms Carcinoma, Ovarian Epithelial