PalbocIclib in PreMenopausal Women With ER Positive/HER-2 Negative MetAstatic Breast Cancer

NCT02917005 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: AMCI-001
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, randomized, multicenter, international phase II study for premenopausal patients with hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. Patients will be randomized to receive either palbociclib + exemestane + OFS (Arm 1) or exemestane +OFS (Arm 2). Treatment will be continued until disease progression, unacceptable toxicities, or withdrawal of consent.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; hormone receptor positive, HER2 negative; palbociclib; premenopausal

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  28 months

Secondary Outcomes (4)

• Overall response rate

  28 months

• Clinical benefit rate

  28 months

• Overall survival

  52 months

• Incidence of treatment related adverse events

  28 months

Study Arms (2)

Palbociclib Arm

EXPERIMENTAL

Palbociclib (Pfizer) 125mg/day orally for 3 weeks followed by 1 week off plus Exemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days

Drug: Palbociclib; Drug: Exemestane; Drug: Goserelin

Control Arm

ACTIVE COMPARATOR

Exemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days

Drug: Exemestane; Drug: Goserelin

Interventions

Palbociclib DRUG

CDK 4/6 inhibitor

Also known as: Ibrance

Palbociclib Arm

Exemestane DRUG

Aromatase inhibitor

Also known as: Aromasine

Control Arm; Palbociclib Arm

Goserelin DRUG

LHRH agonist

Also known as: Zoladex

Control Arm; Palbociclib Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer (histologically or cytologically proven diagnosis of adenocarcinoma of the breast) not amenable to curative treatment by surgery or radiotherapy.
• ER positive tumour: Histological or cytological confirmation of estrogen and/or progesterone-receptor positive, as determined by routine IHC. Positivity is defined as ≥1% positive stained cells. The receptor status determined by utilizing an assay consistent with local laboratory standards.
• HER2 negative breast cancer as confirmed by IHC, SISH or FISH.
• Premenopausal women : (definition of a real menopause is not a simple task in these relatively young women, owing to the potential effect of prior chemotherapy and /or endocrinal therapy particularly OFS) defined either by:
• i. Any age below 40 years , irrespective to E2 level or menstrual history ii. If the woman had a menstrual period any time within the last 12 months iii. If the woman has amenorrhea of more than 12 months (in the absence of chemotherapy or ovarian function suppression) that is associated with serum hormone levels that are NOT in the postmenopausal range (either estradiol (E2) \< 30 pg/mL and follicle-stimulating hormone (FSH) \< 20 mU/mL OR E2 ≥ 30 pg/mL and FSH ≥ 20 mU/mL) \[30\].
• Secondary hormonal resistance to tamoxifen or endocrinal sensitive metastatic disease i. Secondary hormonal resistance is defined as recurrence after 24 months from the start of adjuvant tamoxifen treatment or within 12 months from the end of the 5 years of adjuvant Tamoxifen ii. Endocrinal sensitive disease is defined as recurrence after 12 months from the end of adjuvant tamoxifen treatment or de novo metastatic disease
• Measurable disease according to RECIST or bone-only metastases. Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation.
• i. Patients must either have at least one lesion that can be accurately measured; OR ii. Patients have bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
• ECOG Performance Status 0, 1, \& 2.
• Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade 1 (except alopecia or other toxicities not considered a safety risk for the patient).
• Adequate organ function as defined by the following criteria:
• i. Absolute neutrophil count (ANC) ≥ 1.5 10˄9/L ii. Platelets \> 100 x10˄9/L iii. Hemoglobin (Hgb) \> 9.0g/dL iv. INR \< 2 v. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5x ULN (or \<5 if hepatic metastases are present) vi. Total serum bilirubin \< 1.5 x ULN (\<3 x ULN for patients known to have Gilberts Syndrome) vii. Serum creatinine \< 1.5 x ULN viii. QTc\< 470 msec (based on the mean value of the triplicate ECGs).
• Written informed consent obtained before any trial related activity and according to local guidelines.

You may not qualify if:

• Postmenopausal women. Postmenopausal status is defined by age\>40years with amenorrhea of more than 12 months, associated with serum hormonal levels of the postmenopausal range (either estradiol (E2) \< 30 pg/mL and follicle-stimulating hormone (FSH) \< 20 mU/mL or E2 ≥ 30 pg/mL and FSH ≥ 20 mU/mL) \[30\], in the absence of chemotherapy, tamoxifen, or OFS.
• Patients with primary endocrinal resistance, defined as recurrence within 24 months from the start of adjuvant tamoxifen treatment.
• Symptomatic and/or life threatening visceral metastases i. Diffuse lymphangitic carcinomatosis. ii. Bulky liver or pulmonary metastases
• Patients with only non-measurable lesions other than bone metastasis as defined above (e.g., pleural effusion, ascites, etc.).
• Patients who have received hormonal treatment other than neo/adjuvant tamoxifen
• ± LHRH agonist for their early breast cancer.
• Patients who received prior chemotherapy for metastatic or recurrent breast cancer.
• Another malignancy within 5 years prior to enrolment with the exception of adequately treated in-situ carcinoma of the cervix, uterus, basal or squamous cell carcinoma or non-melanomatous skin cancer.
• Uncontrolled (clinically or radiologically progressive) CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
• Major surgery within 3 weeks of first study treatment.
• Chemotherapy, radiotherapy, or other anti-cancer therapy within 2 weeks before randomization. Patients who previously received radiotherapy to 25% of bone marrow are not eligible independent of when it was received.
• Current treatment with any anti-cancer therapies for advanced disease; any experimental treatment of another clinical trial; therapeutic doses of anticoagulant.
• N.B. Low dose anticoagulants for deep vein thrombosis prophylaxis are allowed. Low molecular weight heparin is allowed. Aspirin is permitted.
• Active bleeding diathesis.
• History of non-compliance to medical regimens. Patients unwilling to or unable to comply with the protocol.

Sponsors & Collaborators

• Hamdy A. Azim: lead

Study Sites (1)

Wits Oncology center

Johannesburg, 2050, South Africa

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; exemestane; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Loay M. Kassem, MD

CONTACT

01003022907; Loay.kassem@cairocure.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: September 18, 2016
• First Posted: September 28, 2016
• Study Start: May 7, 2019
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2023
• Last Updated: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

ZA (1)