A Phase II Randomized Double-blind, Placebo-controlled Study of Alpelisib in Combination With Fulvestrant for Chinese Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, PIK3CA Mutant Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor (AI) Treatment, Including a Subset With Pharmacokinetic Analysis

Plain English Summary

Study Assessing the Efficacy and Safety of Treatment With Alpelisib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Chinese Men and Postmenopausal Women With Advanced Breast Cancer is a Phase 2 clinical trial sponsored by Novartis Pharmaceuticals studying Breast Neoplasms. This trial tests if adding Alpelisib to Fulvestrant is better than Fulvestrant alone for advanced breast cancer. It is for Chinese men and postmenopausal women with a specific type of advanced breast cancer that has a PIK3CA mutation and has not responded to prior treatment. Participants will receive either Alpelisib plus Fulvestrant or a placebo plus Fulvestrant, assigned randomly. Alternative treatments may include other hormone therapies or chemotherapy, depending on the patient's specific situation and prior treatments. The trial aims to enroll 69 participants.

Official Summary

The primary objective is to evaluate whether treatment with alpelisib in combination with fulvestrant prolongs Progression Free Survival (PFS) compared to treatment with placebo in combination with fulvestrant. The primary scientific question of interest is: what is the treatment effect based on PFS for alpelisib in combination with fulvestrant versus placebo in combination with fulvestrant in Chinese men and postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation, who received prior treatment with an aromatase inhibitor (AI) either as (neo) adjuvant treatment or as treatment for advanced disease, regardless of study treatment discontinuation or start of new anti-neoplastic therapy.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are a Chinese man or postmenopausal woman, 18 years or older, with a confirmed PIK3CA mutation in your breast cancer. Your cancer must be hormone receptor-positive, HER2-negative, and advanced (locally recurrent or metastatic). You cannot join if you have received prior treatment with chemotherapy (except for early-stage treatment), fulvestrant, or certain other targeted drugs, or if you have symptomatic visceral disease. This trial is studying Breast Neoplasms, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see if the combination treatment helps patients live longer without their cancer getting worse (Progression Free Survival). The specific primary outcome measures are: Progression Free Survival (PFS) (From the date of randomization to the date of the first documented progression or death due to any cause, up to approximately 34 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for more effective treatments for advanced breast cancer with a specific genetic mutation (PIK3CA) that has stopped responding to standard hormone therapy. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Neoplasms, where improved treatment options are needed.

Investor Insight

This trial targets a specific subset of advanced breast cancer patients, indicating a focus on personalized medicine. Success could lead to a new treatment option for this niche market. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific type of breast cancer you have, the PIK3CA mutation, and if this trial is the best option for you. Participation involves regular clinic visits for medication, blood tests, and scans to monitor your cancer and any side effects. You will be randomly assigned to receive either the study drug combination or a placebo with the standard drug, and neither you nor your doctor will know which you are receiving. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 69 participants

Interventions

• DRUG: Alpelisib — 300mg (oral) once daily, in a 28-day cycle
• DRUG: Fulvestrant — Fulvestrant 500 mg (intramuscular, as two 250mg/5 mL injections) on Day 1 and 15 of Cycle 1 and on Day 1 of every Cycle thereafter
• DRUG: Placebo — 300 mg by mouth once daily, in a 28-day cycle

Primary Outcomes

• Progression Free Survival (PFS) (From the date of randomization to the date of the first documented progression or death due to any cause, up to approximately 34 months)

Secondary Outcomes

• Overall survival (OS) (From date of randomization to date of death due to any cause, up to approximately 48 months.)
• Overall response rate (ORR) (Up to approximately 34 months)
• Clinical benefit rate (CBR) with confirmed response (Up to approximately 34 months)
• Pharmacokinetics (PK): Trough concentration of alpelisib in plasma (Predose at Cycle (C) 1 Day (D) 15, C2 D1, C4 D1 and C6 D1 (Cycle=28 days))
• Time to definitive deterioration in Eastern Cooperative Oncology Group (ECOG) performance status (PS) (Up to approximately 30 months.)

Full Eligibility Criteria

Key Inclusion Criteria:

* Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory. One new or recent biopsy (collected at screening if feasible) or archival tumor block or slides (3 slides minimum from a surgical specimen, or 7 slides minimum from a core needle biopsy) must be provided. It is recommended to provide a tumor sample collected after the most recent progression or recurrence.
* Chinese man or postmenopausal woman ≥ 18 years of age
* Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)
* Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.
* Participant has 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
* Participant has either
* Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation) OR
* If no measurable disease is present, then at least one predominantly lytic bone lesion must be present (Participants with no measurable disease and only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).
* Participant has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
* Participants may be:
* relapsed with documented evidence of progression while on (neo) adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease
* relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease
* newly diagnosed advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy
* Patient has ECOG performance status 0 or 1.
* Patient has adequate bone marrow function.

Key Exclusion Criteria

* Participant with symptomatic visceral disease or any disease burden that makes the Participant ineligible for endocrine therapy per the investigator's best judgment.
* Participant has received prior treatment with chemotherapy (except for (neo)adjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor.
* Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant.
* Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to randomization, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom ≥ 25% of the bone marrow was irradiated.
* Participant has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
* Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II
* Participant has currently documented pneumonitis/interstitial lung disease
* History of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis
* Participant with unresolved osteonecrosis of the jaw
* Participant has a history of severe cutaneous reactions like Stevens- Johnson-Syndrome (SJS), Erythema Multiforme (EM), or Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Other protocol-defined inclusion/exclusion criteria may apply.

Trial Locations

• Novartis Investigative Site, Hefei, Anhui, China
• Novartis Investigative Site, Hefei, Anhui, China
• Novartis Investigative Site, Guangzhou, Guangdong, China
• Novartis Investigative Site, Shijiazhuang, Hebei, China
• Novartis Investigative Site, Harbin, Heilongjiang, China
• Novartis Investigative Site, Zhengzhou, Henan, China
• Novartis Investigative Site, Wuhan, Hubei, China
• Novartis Investigative Site, Changsha, Hunan, China
• Novartis Investigative Site, Nanjing, Jiangsu, China
• Novartis Investigative Site, Nanjing, Jiangsu, China
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Hormone Receptor Positive Breast Cancer
• HER2-Negative Breast Cancer
• Advanced Breast Cancer
• Metastatic Breast Cancer
• Endocrine Therapy Resistance
• PIK3CA Mutations
• Oncology
• Gynecologic Oncology
• Internal Medicine

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