Pilot Decentralized Clinical Trial in Men and Pre and Post-menopausal Women With Breast Cancer and a Specific Mutation (PIK3CA) Treated With Alpelisib in Combination With Fulvestrant

Phase 2

Terminated

Conditions: Advanced Breast Cancer

Interventions: Drug: Alpelisib
Drug: Fulvestrant
Drug: Goserelin

Registration Number: NCT04862143

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The study was designed to identify and register practical observations and experiences in connection with planning and implementing decentralized, patient-centered clinical trials at a geographic distance with virtual elements.

Detailed Description: The purpose of this open-label, single arm, multi-center, Phase II interventional pilot trial was to evaluate if a decentralized clinical trial (DCT) using a telemedicine platform offers a satisfactory, safe and suitable management for HR-positive/HER2-negative participants with advanced breast cancer harboring a PIK3CA mutation and treated with alpelisib plus fulvestrant. The trial utilized a hybrid DCT approach to reduce participant burden by bringing visits, services, and supplies closer to them.

The planned duration of treatment was 12 cycles of 28 days. Participants could discontinue treatment earlier due to unacceptable toxicity, disease progression and/or decision made at the discretion of the investigator or the participant.

On-site visits occurred during screening, at Cycle 1 Day 1 (baseline), and at end-of-trial. Visits at the local oncologist practice were planned on Day 1 of Cycle 2, Cycle 4, Cycle 7, and Cycle 10. Other visits were performed by a district nurse, either at home or at the local oncologist's practice, depending on the participant's preference.

During the on-site visit on Cycle 1, Day 1, participants were trained on using the telemedicine platform, and other monitoring devices used during remote participation: a glucometer and a smartphone with the telemedicine application installed. Study treatment was also initiated during this visit. The participants were then transitioned to remote participation enabled by the telemedicine platform with support of local healthcare providers (local oncologist, district nurse, or other qualified healthcare professional) under the investigator's oversight.

Discontinuation of remote participation was not a reason for trial termination. Participants who did not wish to continue with remote participation had the option to attend on-site visits.

The study planned to enroll approximately 20 participants, however the study was terminated prematurely with only 2 participants enrolled. The decision to terminate the study was due to delays during the start-up period and due to low enrollment. The decision to terminate was not related to any potential safety concern with alpelisib.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

Inclusion Criteria

Participant is an adult ≥18 years old at the time of consent
Participant with ABC (loco regionally recurrent or metastatic) not amenable to curative therapy.
Participant with a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PR-positive breast cancer by local laboratory.
Participant with a confirmed HER2-negative ABC.
Participant with a pathology report confirming PIK3CA mutant status by a certified laboratory using a validated PIK3CA mutation assay (from either tissue or blood).
Participant was willing to operate a smartphone compatible with the software of the medical device and willing to manage applications
Participant was willing to use the telemedicine platform and to follow the remote participant monitoring procedure.

Key

Exclusion Criteria

Participant had received prior treatment with any PI3K, mTOR or AKT inhibitor.
Participant with known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant.
Participant participated in a prior investigational study within 30 days prior to the start of trial treatment or within 5 half-lives of the trial treatment, whichever was longer.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Alpelisib + fulvestrant	Alpelisib	Participants were administered alpelisib at a daily dose of 300 mg for 12 cycles of 28 days and fulvestrant at a dose of 500 mg via intramuscular injection on Cycle 1 Day 1 and Cycle 1 Day 15, and Day 1 of each subsequent cycle up to Cycle 12. Pre-menopausal women also received goserelin at a dose of 3.6 mg on Day 1 of each cycle.
Alpelisib + fulvestrant	Goserelin	Participants were administered alpelisib at a daily dose of 300 mg for 12 cycles of 28 days and fulvestrant at a dose of 500 mg via intramuscular injection on Cycle 1 Day 1 and Cycle 1 Day 15, and Day 1 of each subsequent cycle up to Cycle 12. Pre-menopausal women also received goserelin at a dose of 3.6 mg on Day 1 of each cycle.
Alpelisib + fulvestrant	Fulvestrant	Participants were administered alpelisib at a daily dose of 300 mg for 12 cycles of 28 days and fulvestrant at a dose of 500 mg via intramuscular injection on Cycle 1 Day 1 and Cycle 1 Day 15, and Day 1 of each subsequent cycle up to Cycle 12. Pre-menopausal women also received goserelin at a dose of 3.6 mg on Day 1 of each cycle.

Primary Outcome Measures

Name	Time	Method
Participant Satisfaction Assessed Through the Trial Feedback Questionnaire (TFQ)	Baseline, and on Day 1 of Cycle 4 and 7. Cycle= 28 days	The TFQ was designed to capture the patient's experience during a clinical trial. The questionnaire consisted of 23 questions that assessed various aspects of the trial experience. Each question in the TFQ scored on a scale ranging from 1 (representing the worst response) to 5 (representing the best response). To calculate the total score, the scores obtained from each of the 23 questions were summed up. The resulting sum represented the participant's total score, which could ranged from 23 (indicating the lowest possible score) to 115 (indicating the highest possible score).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Dose Reductions/Interruptions for Alpelisib	From the date of the first study treatment up to the end of treatment, assessed up to 6 months	Number of participants with dose reductions and interruptions for alpelisib
Number of Participants With Adverse Events of Special Interest (AESIs)- Hyperglycemia, Rash and Diarrhea	From the date of the first study treatment up to the end of study, assessed up to 6 months	AESIs (Adverse Events of Special Interest) are defined as events, whether serious or non-serious, that are of scientific and medical concern specific to the sponsor's product or program. These events may require ongoing monitoring and communication by the investigator to the sponsor. For this study, the following AESIs were defined: hyperglycemia, rash, and diarrhea. The number of participants experiencing these events per the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 was evaluated.
Number of Participants With Adverse Events (AEs) Leading to In-clinic Visits	From the date of the first study treatment up to the end of study, assessed up to 6 months	An AE refers to any untoward medical occurrence, such as an unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease. The number of participants with AEs per the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 leading to in-clinic visits was assessed.
Number of Unscheduled In-clinic Visits Per Participant in the Study	From the date of the first study treatment up to the end of study, assessed up to 6 months	Unscheduled in-clinic visits were defined as visits that were originally intended to be conducted remotely but were ultimately carried out on-site, or visits that were not originally scheduled but took place on-site or at the local oncologist's (regional hospital). The total number of unscheduled in-clinic visits per participants was evaluated
Patient Retention on the Decentralized Clinical Trial (DCT) Approach	At 3 and 6 months	Patient retention on the DCT approach was calculated as the percentage of participants on remote monitoring for participants still on treatment
Number of Unscheduled In-clinic Visits	From the date of the first study treatment up to the end of study, assessed up to 6 months	Unscheduled in-clinic visits were defined as visits that were originally intended to be conducted remotely but were ultimately carried out on-site, or visits that were not originally scheduled but took place on-site or at the local oncologist's (regional hospital). The total number of unscheduled in-clinic visits was evaluated
Number of Participants Who Discontinue Treatment Due to Adverse Events (AEs)	From the date of the first study treatment up to the end of treatment, assessed up to 6 months	An AE refers to any untoward medical occurrence, such as an unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease. The number of participants who discontinued the treatment due to adverse events was evaluated
Number of Unscheduled In-clinic Visits Because of Safety Reasons	From the date of the first study treatment up to the end of study, assessed up to 6 months	Unscheduled in-clinic visits were defined as visits that were originally intended to be conducted remotely but were ultimately carried out on-site, or visits that were not originally scheduled but took place on-site or at the local oncologist's (regional hospital). The total number of unscheduled in-clinic visits that were prompted by safety reasons was evaluated
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	Baseline, and on Day 1 of Cycle 4, and 7 and end of treatment, assessed up to 6 months. Cycle= 28 days	The EORTC QLQ-C30 questionnaire contained 30 items and was composed of both multi-item scales and single item measures. These included five functional scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact), and a global health status/quality of life (QoL) scale. All of the scales and single items ranged from 0 to 100. A high scale score represented a higher response level. Thus, a high score for a functional scale indicated a high/healthy level of functioning, a high score for the QoL indicated high QoL, but a high score for a symptom scale/single item indicated a high level of symptomatology/problems. The EORTC QLQ-C30 scores for all functional and symptom scales were evaluated
Brief Pain Inventory Short Form (BPI-SF) Scores	Baseline, and on Day 1 of Cycle 4, and 7 and end of treatment, assessed up to 6 months. Cycle= 28 days	The BPI-SF was a questionnaire used to assess pain intensity and interference with daily activities. The Pain Severity Subscale included four questions asking individuals to rate their pain intensity on a scale from 0 to 10, with higher scores indicating more severe pain. The Pain Interference Subscale consisted of seven items that assessed how pain had interfered with activities, rated on the same scale. Both subscales had a total score range of 0 to 10, with higher scores indicating more significant pain or interference.
Number of Participants With Progression-free Survival (PFS) According to RECIST 1.1	Up to 6 months	The number of participants with PFS was defined as the count of participants who did not experience disease progression or death due to any cause during the study. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on local radiology review.
EuroQol 5-Dimension 5-Level (EQ-5D-5L)- Visual Analog Scale (VAS) Score	Baseline, and on Day 1 of Cycle 4, and 7 and end of treatment, assessed up to 6 months. Cycle= 28 days	The 5-level EQ-5D (EQ-5D-5L) questionnaire is a standardized measure of health status. The EQ-5D descriptive system comprises of the 5 following dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Along with the five dimensions of health, the EQ-5D-5L includes a VAS where respondents rate their overall health status on a scale from 0 to 100, where 0 represents the worst possible health state and 100 represents the best possible health state. The EQ-5D-5L VAS scores were evaluated