A Study in Patients With Advanced Breast Cancer

Advanced Breast Cancer Clinical Trial

Official title:

A Phase 1 Study to Determine Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of SCO-120 in Hormone Receptor Positive, HER-2 Negative Advanced Breast Cancer Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04942054
• Other study ID #: SCO-120-19-22
• Status: Terminated
• Phase: Phase 1
• Start date: May 20, 2022
• Est. completion date: February 28, 2023

Study information

• Verified date: May 2023
• Source: Sun Pharma Advanced Research Company Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 1, Open label, Dose escalation and Dose expansion study of SCO-120 in HR +ve HER2-ve advanced/ metastatic breast cancer (MBC) patients to evalaute the safety, tolerability and prelimnary efficacy. Initial part with dose escalation is to determine the MTD and RP2D, and PK and PD characterisation. RP2D will be further evalauted for prelimnary efficacy in MBC patients with tretament failure on Aromatase Inhibitor/Fulvestrant/CDK4-6 inhibitors with or with out ESR1 mutation.

Description:

Part 1 & 2: Approximately 51 subjects will be enrolled Part 3: Approximately 90 subjects will be enrolled

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: February 28, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. All 3 parts of Study:

• Male or females, Age 18 years or older

• Histologically or cytologically diagnosed with ER+/HER2- adenocarcinoma of the breast cancer with an evidence of metastatic/loco-regionally recurrent disease/unresectable advanced disease not amenable to treatment with curative intent

• Documentation of ER-positive, HER2-negative status determined based on a biopsy performed at or after diagnosis of local or metastatic recurrence, utilizing an assay consistent with local standards

• Not more than 3 prior chemotherapeutic regimens

• ECOG performance status 0-1.

• Resolution of all adverse events of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE v 5.0 Grade =1 (except alopecia)

• Adequate organ and immune system function as indicated by laboratory values

• Patients of childbearing potential must practice an acceptable method of birth control as judged by the Investigator

• Female subjects must be non-lactating and non-breast feeding

• Male subjects should not father a child and must practice an acceptable method of birth control measures Willing and available to participate for the entire study

• Willing and able to comply with protocol requirements

2. For Part 1& 2:

• Patient must have evaluable disease (according to RECIST 1.1).

• Documented disease progression or resistance to at least 1 prior endocrine therapy (with or without CDK 4/6 therapy).

3. For Part 3

• Patient must have measurable lesions (according to RECIST 1.1)

• Part 3a: HR+ve, HER2- MBC patients with ESR1 mutations, resistance to atleast one priro endocrine therapy

• Part 3b: HR+ve HER2- MBC patients resistant to atleast one priro endocrine therapy

• Part 3c: HR+ve HER2- MBC patients resistant to atleast one priro endocrine therapy, disease progression on Fulvestrant and CDK4/6i

• Part 3d: Brain metastases secondary to ER+ve HER-ve Breast Cancer:

Measurable brain lesion (= 1) as per RANO-BM Criteria, Tretament naive/ Treated- Stable/ Not requiring immediate local therapy known/ Suspected leptomeningeal disease on Stable corticosteriod dose for 7 days prior screeing

Exclusion Criteria:

1. All 3 parts of Study

• Major surgery <4 weeks of C1D1

• Evidence of organ dysfunction or inadequate bone marrow reserve or any clinically significant finidngs

• Patients with visceral crisis or impending visceral crisis and rapidly progressing disease

• Serology tests +ve for HIV, HCV, HBsAg

• Inability to swallow oral medication

• H/o any relevant allergy/hypersensitivity/idiosyncrasy to drugs/ chemically related to Study drug or its excipients

• Received an IMP within 30 days/5 half life to C1D1

• Prior treatment with other oral SERDs

• Use of concomitant medication that might reasonably influence the results or interpretation of the study

• Requires concurrent systemic anticancer treatment at any time during the study treatment period

• Known or suspected history of significant drug abuse/Alcohol as judged by the Investigator

• Known or suspected history of excessive intake of alcohol in the 12 months prior to study entry

• Malabsorption syndrome/IBD/other illness that would affect oral absorption of Study drug

• Uncontrolled intercurrent illness that would limit compliance with study requirements / have impact on endpoints / safety

• =6 months H/o MI/unstable angina, ongoing > G2 cardiac dysrhythmia, prolonged QTcF/ uncontrolled AF, coronary/peripheral artery bypass graft, HF of NYHA_Class II or greater and CVA (+TIA)

• H/o Endometrial intraepithelial neoplasia, other malignancy < 5 yrs prior to enrollment

• Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, or leptomeningeal disease as indicated by clinical symptoms (not applicable to Part 3d), carcinomatous meningitis, cerebral edema, and/or progressive growth or pulmonary lymphangitic metastases.

• Current abnormal vaginal bleeding or symptomatic endometrial disorders.

2. For Part 2: Use of other ET that block the estrogen receptor: atleast 8 weeks before enrollment (28 weeks for fulvestrant) For Part 2: Liver-only metastases (are not evaluable by FES-PET/CT imaging)

3. For Part 3: Any brain lesion requiring immediate local therapy (which includes but is not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases) Requires increase in the dose of corticosteroids for control of CNS symptoms due to brain metastases Poorly controlled (> 2 per month ) generalized or complex partial seizures Who are taking concurrent enzyme-inducing antiepileptic drugs (EIAED) Who has evidence of significant (ie, symptomatic) intracranial haemorrhage Contra indications for repeated MRI assessments

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms
• HER2-negative Breast Cancer
• Hormone Receptor-positive Breast Cancer

Intervention

Drug:
• Part 1
Dose escalation cohort
• Part 2
Pharmacodyanamic (PD) dose exploration cohorts
• Part 3
Dose expansion at dose(s) = maximum tolerated dose (MTD) cohort

Locations

Country	Name	City	State
India	HealthCare Global Enterprises Ltd	Bangalore	Karnataka
India	HCG Manavata cancer Centre	Nashik	Maharashtra
India	LMMF's Deenanath Mangeshkar Hospital & Research Centre	Pune	Maharashtra
India	Noble Hospital Pvt. Ltd.,	Pune	Maharashtra
United States	The University of Chicago	Chicago	Illinois
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
Sun Pharma Advanced Research Company Limited

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	pharmacodynamic biomarker	Pharmacodynamic Biomarkers [Estrogen receptor (ER) expression, Ki67 down regulation from Tissue Biopsy, and Estrogen receptor occupancy with [(18)F] Fluoroestradiol Positron Emission Tomography (18F-FES PET) scan]	At Screening and End of Cycle 1' (Each Cycle of 28 days)
Primary	Incidence of dose limiting toxicities at each dose levels (Part 1 only)		28 Days/End of Cycle 1
Primary	Incidence and severity of adverse events with each dose level	The intensity of adverse events will be graded as per CTCAE, Version 5.0 and categorized as serious adverse events or non-serious adverse events.	upto 30 days of last dose
Secondary	evaluation of Cmax (Part 1 and Part 2)	Pharmacokinetic analysis will be performed using non-compartmental analysis. The actual elapsed time from dose will be used in the final pharmacokinetic parameter calculations	Through Cycle 1 and Cycle 2 (Each cycle of 28 Days)
Secondary	evaluation of tmax (Part 1 and Part 2)	Pharmacokinetic analysis will be performed using non-compartmental analysis. The actual elapsed time from dose will be used in the final pharmacokinetic parameter calculations	Through Cycle 1 and Cycle 2 (Each cycle of 28 Days)
Secondary	evaluation of AUC (Part 1 and Part 2)	Pharmacokinetic analysis will be performed using non-compartmental analysis. The actual elapsed time from dose will be used in the final pharmacokinetic parameter calculations	Through Cycle 1 and Cycle 2 (Each cycle of 28 Days)
Secondary	tumour response		Every 8 weeks, for 'Time point Response (Partial Response[PR], Stable Disease[SD], Disease progression [DP] or Complete Response [CR]), Through study completion, an average of 1 year.