A clinical trial to study the effect of Alpelisib plus fulvestrant in Indian Patients with advanced or metastatic breast cancer (ABC or MBC) with a PIK3CA mutation

Phase 4

Active, not recruiting

• Conditions: Malignant neoplasm of breast of unspecified site,

• Registration Number: CTRI/2022/04/042205
• Lead Sponsor: Novartis Healthcare Pvt Ltd

Brief Summary

This is a Phase IV prospective multicenter open label non comparative interventional study to assess the safety of alpelisib plus fulvestrant, in men and post-menopausal women with HR positive HER2 negative aBC or MBC with a PIK3CA mutation whose disease has progressed on or after endocrine-based treatment.

The study will include a total of 100 participants. During the treatment phase, treatment will be administered as alpelisib 300 mg orally once daily dosing schedule starting on Cycle 1 Day 1 in combination with fulvestrant i.m. 500 mg on Cycle 1 Day 1 and Day 15 and Day 1 of every cycle thereafter ± 3 days in a 28 days cycle.

The planned duration of treatment is 6 months. Participants may be discontinued from treatment earlier due to unacceptable toxicity disease progression, or if treatment is discontinued at the discretion of the investigator or the participant. For participants who were ongoing on treatment at the end of the planned duration of study and, in the opinion of the investigator are still deriving clinical benefit from alpelisib every effort will be made to continue provision of study treatment via post trial access.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-08-16
• Last Update Posted: 2024-08-20

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Written informed consent obtained before any trial related activities and according to local guidelines.
• Participants with confirmed PIK3CA mutant ABC or MBC whose disease has progressed on or after endocrine based treatment 3.
• Postmenopausal females and males more than or equal to 18 years old with confirmed HR positive HER2 negative advanced or metastatic breast cancer.
• Postmenopausal status is defined either by: i) Prior bilateral oophorectomy ii) Age equal to or more than 60 y iii) Age less than 60 y and amenorrheic for 12 or more months in the absence of chemotherapy tamoxifen toremifene or ovarian suppression and Follicle stimulating Hormone FSH and estradiol in the postmenopausal range per local normal range Note: For women with therapy induced amenorrhea serial measurements of FSH andor estradiol are needed to ensure postmenopausal status.
• Ovarian radiation or treatment with a luteinizing hormone-releasing hormone agonist LH-RHa goserelin acetate or leuprolide acetate is not permitted for induction of ovarian suppression in this trial.
• Participant has adequate bone marrow and organ function that is considered appropriate to receive study treatment, as per the Investigator’s clinical judgement.
• Adequate liver function as shown by i) In absence of liver metastases alanine aminotransferase ALT and aspartate aminotransferase AST Less than 3 × ULN.
• ii) If the Participant has liver metastases ALT and AST less than or equal to 5 × ULN elevated AST or AST values must be stable for 2 weeks without evidence of biliary obstruction by imaging done at Investigator’s discretion.
• iii) Total bilirubin less than 2 × ULN any elevated bilirubin should be asymptomatic at enrollment except for Participants with Gilbert’s syndrome who may only be included if the total bilirubin is less than or equal to 3.0 × ULN or direct bilirubin less than or equal to 1.5 × ULN 6.
• Fasting plasma glucose FPG less than or equal to 140 mg/dL 7.7 mmol/L and glycosylated hemoglobin HbA1 less than or equal to 6.4% both criteria have to be met.
• ECOG Eastern Cooperative Oncology Group Performance Status less than 2 9.
• Fasting Serum amylase less than or equal to 2 × ULN and Fasting Serum lipase less than or equal to ULN 10.
• Potassium within normal limits or corrected with supplements 11.
• Calcium corrected for serum albumin and magnesium within normal limits or less than or equal to grade 1 if judged clinically not significant by the investigator.

Exclusion Criteria

• Known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant 2.
• Participant ineligible for endocrine therapy per the investigators judgment 3.
• Participant has received prior treatment with any PI3K inhibitors and/or mTOR inhibitor 4.
• Participant with type I diabetes or not controlled type II based on FPG and HbA1c see inclusion criterion 7 5.
• Participant has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated basal or squamous cell carcinoma non melanomatous skin cancer or curatively resected cervical cancer 6.
• Participant has not recovered to grade 1 or better from related side effects of prior anticancer therapy with the exception of alopecia 7.
• Participants receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry except in cases outlined below Topical applications inhaled sprays eye drops or local injections are allowed.
• Participants on stable low dose of corticosteroids for at least two weeks prior to enrollment are allowed 8.
• Bilateral diffuse lymphangitic carcinomatosis 9.
• Participants with a known history of HIV seropositivity.
• Screening for HIV infection at baseline is not required 10.
• Active, bleeding diathesis, or on oral anti-vitamin K medication.
• Participant has impairment of gastrointestinal GI function or GI disease that may significantly alter the absorption of the study drugs 12.
• Participant has any other concurrent severe and/or uncontrolled medical condition that would in the investigators judgment contraindicate participation in the clinical study.
• Participant has documented pneumonitis/interstitial lung disease which is active and requiring treatment 14.
• Participants with unresolved osteonecrosis of the jaw 16.
• Participant has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome SJS Erythema Multiforme EM Toxic Epidermal Necrolysis TEN or Drug Reaction with Eosinophilia and Systemic Symptoms DRESS.
• Participant is a woman of child-bearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and at least for 1 week for alpelisib or 1 year for fulvestrant based on prescribing label after the last dose of each study drug whichever comes later.
• Highly effective contraception methods include: i) Total abstinence when this is in line with the preferred and usual lifestyle of the Participant.
• Periodic abstinence e.g calendar ovulation symptothermal postovulation methods and withdrawal are not acceptable methods of contraception ii) Female sterilization have had surgical bilateral oophorectomy with or without hysterectomy total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment.
• In case of oophorectomy alone only when the reproductive status of the woman has been confirmed by follow up hormone level assessment iii) Male sterilization at least 6 months prior to screening.
• For female Participants on the study the vasectomized male partner should be the sole partner for that Participant iv) Placement of an intrauterine device IUD or intrauterine system IUS without hormonal component.
• Use of oral estrogen and progesterone injected or implanted combined hormonal method of contraception or placement of an intrauterine device IUD or intrauterine system IUS or forms of hormonal contraception that have comparable efficacy failure rate Less than 1% for example hormonal vaginal ring or transdermal hormone contraception.
• In case of use or oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
• Note: Women are considered postmenopausal and not of child bearing potential if they have had 12 months of natural spontaneous amenorrhea with an appropriate clinical profile i.e age appropriate history of vasomotor symptoms or have had surgical bilateral oophorectomy with or without hysterectomy total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment.
• In the case of oophorectomy alone only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
• Participant is a sexually active male unwilling to use a condom during intercourse while taking study treatment, and for 1 week for alpelisib or 1 year for fulvestrant based on prescribing label after stopping each study drug whichever comes later.
• A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the safety of alpelisib plus fulvestrant.	Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and End of Treatment Visits.

Secondary Outcome Measures

Name	Time	Method
To assess the safety of alpelisib plus fulvestrant.	Screening, Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, End of Treatment, Safety Follow Up (30 days after EOT).

Trial Locations

Locations (17)

AIIMS; 🇮🇳 Raipur, CHHATTISGARH, India

AIIMS All India Institute of Medical Sciences; 🇮🇳 Delhi, DELHI, India

Bellevue Clinic; 🇮🇳 Kolkata, WEST BENGAL, India

Chittaranjan National Cancer Institute; 🇮🇳 Kolkata, WEST BENGAL, India

CIMETs Inamdar Multispeciality Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Dr. Bhubaneswar Borooah Cancer Institute; 🇮🇳 Kamrup, ASSAM, India

Jawaharlal Nehru Cancer Hospital And Research Centre; 🇮🇳 Bhopal, MADHYA PRADESH, India

KIMS Kingsway Hospital; 🇮🇳 Nagpur, MAHARASHTRA, India

Mahatma Gandhi Cancer Hospital & Research Institute; 🇮🇳 Visakhapatnam, ANDHRA PRADESH, India

Malabar Cancer Centre; 🇮🇳 Kannur, KERALA, India

Scroll for more (7 remaining)

AIIMS

🇮🇳Raipur, CHHATTISGARH, India

Dr Amit Kumar Agarwal

Principal investigator

8853858850

mitu1505@gmail.com