HR+/HER2- Advanced Breast Cancer and Endocrine Resistance

NCT03322215 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 2016-002893-11
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 9

Brief Summary

This is a randomized, 2-arm, open-label, multicenter, international phase II trial. A total of 196 patients will be included. The study will include patients with metastatic Hormone Receptor positive / Human Epidermal Growth Factor Receptor (HER2) negative breast cancer with progressive disease after endocrine treatment. Patients will be randomized (1:1) between two treatment arms: A. palbociclib + fulvestrant and b. capecitabine.

Conditions

Breast Cancer Metastatic

Keywords

palbociclib; fulvestrant; capecitabine

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS), as assessed locally by the investigator.

  Time to progression will be measured according to the RECIST criteria (version 1.1). Response criteria are essentially based on a set of measurable lesions identified at baseline as target lesions, and - together with other lesions that are denoted as non-target lesions - followed until disease progression.

  Time from the date of randomization to the date of progression, assessed up to 5 years.

Secondary Outcomes (15)

• Health related quality of life score EuroQol (EQ-5D)

  Baseline to progression up to 2 years

• Health related quality of life score EORTC QLQ-C30

  Baseline to progression up to 2 years

• Health related quality of life score EORTC QLQ-BR23

  Baseline to progression up to 2 years

• Correlation of efficacy measures with tumor Biomarkers

  Correlative analyses will be performed after the end of the trial. PFS is defined as time from the date of randomization to the date of progression assessed up to 5 years..

• Correlation of efficacy measures with tumor Biomarkers

  Correlative analyses will be performed after the end of the trial. PFS is defined as time from the date of randomization to the date of progression assessed up to 5 years.

Study Arms (2)

Palbociclib and fulvestrant

EXPERIMENTAL

Combination of palbociclib and fulvestrant Palbociclib: 125 mg capsule administered orally once daily for 21 consecutive days followed by 7 days off treatment. Dose modification is recommended based on individual safety and tolerability. Fulvestrant: 500 mg administered intramuscularly on days 1 and 15 of cycle 1, and then on day 1 of each subsequent 28-day cycle.

Drug: Palbociclib; Drug: Fulvestrant

Capecitabine

ACTIVE COMPARATOR

1,000 mg/m2 tablet administered orally twice daily for 2 weeks followed by one week of rest. Depending on adverse reactions, both dose escalation and dose reductions will be performed.

Drug: Capecitabine

Interventions

Palbociclib DRUG

75-125 mg capsule orally once daily for 21 consecutive Days followed by 7 Days of treatment.

Also known as: Ibrance

Palbociclib and fulvestrant

Fulvestrant DRUG

500 mg intramuscularly Days 1 and 15 of cycle 1, and then on Day 1 of each subsequent 28-days cycle.

Also known as: Faslodex

Palbociclib and fulvestrant

Capecitabine DRUG

Oral tablet 500 - 1,250 mg/m2 twice Daily, for 2 weeks followed by 1 week of rest.

Also known as: Xeloda

Capecitabine

Eligibility Criteria

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

You may qualify if:

• Women 18 years or older.
• Postmenopausal, defined by at least one of the following criteria:
• Prior bilateral oophorectomy
• Age ≥60
• Age \<60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and estradiol in the postmenopausal range according to the local laboratory reference. Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure postmenopausal status. OR Pre/perimenopausal if treated with goserelin that was initiated at least 4 weeks prior to randomization.
• Locally advanced or metastatic breast cancer deemed not amenable to curative surgery or curative radiation therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Known estrogen-receptor positive and/or progesterone receptor positive breast cancer reported by local laboratory.
• Known HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
• Documented resistance to endocrine therapy (tamoxifen or aromatase inhibitors) defined as:
• Recurrence while on or within 12 months after the end of adjuvant endocrine treatment OR
• Progression while on or within 1 month after the end of endocrine treatment for advanced disease
• Previous chemotherapy for breast cancer including an anthracycline and a taxane (only one line for metastatic disease) is permitted.
• Radiological or other objective evidence (eg. new skin lesions or new lymph node lesions) of recurrence during or after the most recent systemic therapy for recurrent / metastatic disease prior to randomization.
• At least one tumor lesion accessible for biopsy that is a non-bone lesion or a predominantly lytic bone lesion, and that measures at least 10 mm in largest diameter. This lesion must not have been treated previously with irradiation (although the area may have been irradiated before the occurrence of the lesion).

You may not qualify if:

• Previous treatment with a CDK4/6 inhibitor, mTOR or PI3K inhibitor, fulvestrant or capecitabine. Short-term (\<28 days) exposure to mTOR or PI3K inhibitor in the (neo)adjuvant setting is allowed.
• More than one prior chemotherapy lines for metastatic breast cancer. Previous (neo)adjuvant chemotherapy or for radically treated local or regional relapse is allowed in addition to one prior chemotherapy line for metastatic breast cancer Note: A chemotherapy line in advanced disease is an anticancer regimen that contains at least one chemotherapy agent and is given for 21 days or longer. If a cytotoxic chemotherapy regimen was discontinued for a reason other than disease progression and the decision for its discontinuation was taken within 21 days after starting it, then this regimen does not count as a "prior line of chemotherapy". Chemotherapy regimens composed of more than one drug are considered as one line of therapy.
• No measurable lesions amenable to biopsy (e.g. pleural effusion, ascites, skin rash, sclerotic bone etc).
• CNS metastases unless asymptomatic and adequately controlled with surgery or radiotherapy. Stable CNS disease is defined as CNS metastases or cord compression that have been definitively treated and the patient is clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
• Leptomeningeal carcinomatosis
• Advanced, symptomatic visceral spread (visceral crisis) with risk of life-threatening complications in the short term.
• Concurrent malignancy of any site, except adequately controlled limited basal cell carcinoma or squamous-cell carcinoma of the skin, in situ melanoma or carcinoma in situ of the cervix.
• Active cardiac disease or a history of cardiac dysfunction including any of the following:
• History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Documented cardiomyopathy
• QTc \> 480 msec as measured by Bazett's formula, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
• Uncontrolled hypertension.
• Patients being treated with drugs recognized as strong inhibitors or inducers of the isoenzyme CYP3A (including, but not limited, to - see table 6 - Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itraconazole, Voriconazole, Ritonavir, Telithromycin) continuously for at least 7 days during any time period in the last 2 weeks prior to randomization.
• Subjects with known dihydropyrimidine dehydrogenase (DHPD) deficiency or previous severe reactions to a fluoropyrimidine.

Sponsors & Collaborators

• Theodoros Foukakis: lead

Study Sites (9)

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Skåne University Hospital

Malmo, 205 02, Sweden

Location

S:t Görans Hospital

Stockholm, 112 19, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Uppsala University Hospital

Uppsala, 751 85, Sweden

Location

NHS Grampian

Aberdeen, AB15 6RE, United Kingdom

Location

Western General Hospital

Edinburgh, EH1 3EG, United Kingdom

Location

Beatson

Glasgow, G12 0XH, United Kingdom

Location

NHS Ayshire and Arran

Kilmarnock, KA2 OBE, United Kingdom

Location

MeSH Terms

Interventions

palbociclib; Fulvestrant; Capecitabine

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

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: Principal Investigator

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 26, 2017
• Study Start: October 24, 2017
• Primary Completion: April 30, 2021
• Study Completion: October 31, 2023
• Last Updated: March 8, 2024

Record last verified: 2023-05

Locations

SE (5); GB (4)