Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Neoplasm Metastasis

Neoplasms, Second Primary

Brain Neoplasms

Meningeal Carcinomatosis

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Meningeal Neoplasms

All Drugs and Chemicals

GDC-0084

Enzyme Inhibitors

GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily, with a potential de-escalation cohort to 30mg, to determine MTD in combination with whole brain radiation therapy radiation therapy to 30Gy in 10 fractions. Once MTD is determined, 12 additional patients will be treated with GDC-0084 at MTD in combination with whole brain radiation therapy.

GDC-0084 in 3 + 3 dose-escalation in 3 cohorts: 45, 60, 75 mg daily

whole brain radiation therapy radiation

Brandon Imber, MD, PhD

This study will test the safety of the study drug, GDC-0084, in combination with radiation therapy in people who have solid tumor brain metastases or leptomeningeal metastases. All participants will have cancer with a PIK3CA mutation. The researchers will test increasing doses of GDC-0084 to find the highest dose that causes few or mild side effects in participants. The study will also try to find out if the combination of the study drug with radiation is effective against participants' cancer.

GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases

A Phase I Study With Expansion Cohort of Concurrent GDC-0084 With Radiation Therapy for Patients With Solid Tumor Brain Metastases or Leptomeningeal Metastases Harboring PI3K Pathway Mutations

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Four dose levels will be examined and the maximum tolerated dose (MTD) will be identified.

The standard 3+3 dose-escalation scheme for this study is as follows. Patients will be accrued to the study in cohorts of 3. For any given dose an initial cohort of 3 patients will be treated at that dose.The dose level will be escalated if none of the 3 exhibits any dose limiting toxicity (DLT).

For patients with brain metastases, response determination will be determined using Response Assessment in Neuro-Oncology Brain Metastases criteria28. For patients with leptomeningeal metastases, response assessment will be determined by investigator based on MRI.

Kazia Therapeutics

Memorial Sloan Kettering Cancer Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Hormones

Fulvestrant

Mitogens

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC)/ metastatic breast cancer (MBC) patients

Patients with Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) gene mutation positive

Prospective observational study. There is no treatment allocation. Patients administered alpelisib plus fulvestrant, that have started before inclusion of the patient into the study will be enrolled.

alpelisib plus fulvestrant

Novartis Pharmaceuticals

SPEAR is a non-interventional / observational, prospective, multicenter study planned to be conducted across \~ 30 sites in India, among HR-positive and HER2-negative ABC/MBC patients. This being a non-interventional study, no investigational drug or intervention will be administered as a part of the study participation. All the therapeutic decisions, as well as the type and timing of disease monitoring, laboratory tests or medical procedures will be at the discretion of the treating physician and upon patient's consent. No visits will be scheduled as a part of this non-interventional study, however, data by visits for variables will be collected for all the enrolled patients.

Overall, this study will have 2 parts (Part A and Part B). However, it is to be noted that, these parts (Part A and Part B) are independent of each other and can run in parallel. The purpose of the Part A of study is to determine the proportion of PIK3CA mutation positive patients among the HR-positive and HER2-negative ABC/MBC diagnosed patients in India. The Part B of the study aims to evaluate the clinical effectiveness and tolerability of alpelisib plus fulvestrant among men, pre-menopausal women (ovarian ablation) or post-menopausal women who are PIK3CA mutation positive patients with HR-positive and HER2-negative ABC/MBC diagnosis among Indian population, in the real-world setting.

Part A- This will involve enrolling of approximately 1200 patients (males, post-menopausal women or pre-menopausal women who are receiving ovarian ablation) with a documented diagnosis of HR-positive HER2-negative ABC/MBC. The data on PIK3CA mutation status will be collected only for those patients who signs ICF for participation in the study. Once, patient signs ICF, their samples will be sent for PIK3CA mutation status testing, that will be performed at central laboratory and the results on mutation status will be reported to the investigator.

Part B- This part aims to enroll approximately 200 patients who are PIK3CA mutation positive. The patients enrolled into the Part B of the study can either be continued from Part A of the study or be a direct enrollment into the Part B of the study. For the patient's entering directly into Part B of the study, positive PIK3CA status should be available prior to study entry. All the patients entering into part B of the study must be alpelisib treatment naïve. The patients enrolled into Part B of the study, should have already been planned to receive treatment with alpelisib plus fulvestrant, based on their treating physician's discretion and upon patient's consent. The treatment decision by the physician are to be made independent of the patient's inclusion in this observational study. During the Part B of the study, data by visits for variables will be collected for the enrolled patients at every 3 months interval (±1 month), if feasible or until a maximum of 24 months observational period or lost to follow-up (End-of-study \[EoS\] assessment will be performed), or death, or disease progression, whichever occurs first.

Study of PIK3CA Mutations and Effectiveness and Tolerability Outcomes of Alpelisib in Real-world

A Descriptive Study of PIK3CA Mutations and Outcomes With Alpelisib in Patients With HR-positive and HER2-negative Advanced Breast Cancer (ABC)/ Metastatic Breast Cancer (MBC) in India

Defined as whether PIK3CA mutation is detected (positive or negative) after the enrollment of patient in Part A of the study.

The mutation status should specify each 11 hotspots (C420R, E542K, E545A,E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, and H1047Y)

CBR defined as the proportion of patients with a best overall response of CR (complete response) or PR (partial disease), or an overall lesion response of stable disease (SD) or non-CR/non-PD (progressive disease) which lasts for a minimum time duration (with a default of at least 24 weeks in breast cancer studies). This should be evaluated as per RECIST v1.1. This endpoint measures signs of activity considering duration of disease stabilization

Two sub-groups will be identified based on age as \<75 years and ≥75 years for patient's data collection

Receptor expression can be:

* ER: Estrogen Receptor
* PgR: Progesterone Receptor
* HER2: Human Epidermal Growth Factor Receptor 2

Disease free interval (DFI) is defined as the interval from the completion of therapy to the diagnosis of recurrence

At advanced / metastatic disease diagnosis number of metastasis will be collected

At advanced / metastatic disease diagnosis location of metastasis will be collected

To identify the treatment patterns of prior therapies received for ABC/MBC, as available in the patient's medical record, prior number of Line of Therapy (LoT) for the advanced / metastatic disease will be collected

To identify the treatment patterns of prior therapies received for ABC/MBC, as available in the patient's medical record, prior treatment type (hormone alone, hormone with targeted therapy (TT), chemotherapy, etc.) will be collected

To identify the treatment patterns of prior therapies received for ABC/MBC, as available in the patient's medical record, prior treatment sequence by Line of Therapy (LoT) will be collected

To identify the treatment patterns of prior therapies received for ABC/MBC, as available in the patient's medical record, time to next treatment will be collected.

Time to next treatment: defined as time gap between two Line of Therapy (LoT), as applicable

To identify the treatment patterns of prior therapies received for ABC/MBC, as available in the patient's medical record, reason (s) for discontinuation of prior therapy will be collected

To identify the treatment patterns of prior therapies received for ABC/MBC, as available in the patient's medical record, PIK3CA mutation positive patients not prescribed alpelisib will be collected by reason

Defined as the time from start of treatment with alpelisib plus fulvestrant (index date) to the date of the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

ORR is defined as the proportion of patients with best overall response of Complete Response (CR) or partial response (PR) evaluated based on local investigator's assessment according to RECIST 1.1

Calculated as the time from the date of the first documented Complete Response (CR) or partial response (PR) per RECIST version 1.1.

The laboratory assessment will be recorded at baseline and during the study observation period based on changes in Grade of laboratory abnormality.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases	NCT04192981	Brain Metastase... Leptomeningeal ...	GDC-0084 whole brain rad...	18 Years -	Memorial Sloan Kettering Cancer Center
Study of PIK3CA Mutations and Effectiveness and Tolerability Outcomes of Alpelisib in Real-world	NCT05022342	Breast Cancer	alpelisib plus ...	18 Years - 100 Years	Novartis
GDC-0084 With Radiation Therapy for People With PIK3CA-Mutated Solid Tumor Brain Metastases or Leptomeningeal Metastases	NCT04192981	Brain Metastase... Leptomeningeal ...	GDC-0084 whole brain rad...	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for pik3ca mutations