Advanced Breast Cancer, Advanced or Metastatic Breast Cancer, Metastatic Breast Cancer (HR+/ HER2-), Metastatic Colorectal Adenocarcinoma
Conditions
Keywords
Carcinoma, Breast, Estrogen Receptor Positive Breast Cancer, HER2- Breast Cancer, Colon Cancer, PI3K mutation
Brief summary
The purpose of this study is to learn about the safety and effects of the study medicine (called PF-08165784) when given alone or together with other anti-cancer therapies. Anti-cancer therapy is a type of treatment given to stop the growth of cancer. This study also aims to find the best amount of study medication that can be given to patients. This study is seeking participants with a specific type of breast cancer (BC) called hormone receptor-positive (HR+), HER2- negative (HER2-) breast cancer, or colorectal cancer (CRC) (cancer of the colon or rectum), that has a change (mutation) in a gene called PIK3CA. The cancer must be advanced or metastatic, meaning it has spread to other parts of the body or cannot be completely removed with surgery. All participants in this study will take the study medication (PF-08165784) as a tablet by mouth. The participant may take the medicine at the study clinic during study visits or at home. Treatment will be given in 28-day cycles and will continue for as long as the participant remains in the study. Depending on which part of the study participants are enrolled into, they will receive the study medication (PF-08165784) alone or in combination with other anti-cancer medications.
Interventions
DRUGPF-08165784
Taken by mouth (PO)
DRUGFulvestrant
Selective Estrogen Receptor Degrader (SERD)
DRUGAtirmociclib
Selective cyclin-dependent kinase 4 (CDK4) inhibitor
DRUGCetuximab
Monoclonal antibody (EGFR inhibitor)
DRUGLetrozole
Nonsteroidal aromatase inhibitor
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Advanced or metastatic cancer of the breast or colon Part 1A, 1B, and 1C: HR+/HER2- advanced or metastatic breast cancer with disease progression after at least 1 line of treatment with an endocrine therapy and cyclin-dependent kinase (CDK)4/6 inhibitor in the advanced or metastatic setting and received no more than 1 line of prior cytotoxic and/or 1 line of prior antibody-drug conjugate (ADC) therapy in the metastatic setting Part 1D: Metastatic or advanced colorectal cancer with at least having received chemotherapy and/or targeted therapy if appropriate Part 2A: HR+/HER2- advanced or metastatic breast cancer with no prior systemic therapy or chemotherapy for advanced or metastatic disease * Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutation * Archived tumor specimen or fresh tumor biopsy * Measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Exclusion criteria
* Active or clinically significant dermatologic conditions * Active malignancy within 3 years prior to enrollment * Advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term * Major surgery or radiation therapy within 3 weeks prior to study entry * Prior irradiation to \>25% of the bone marrow * Active or history of pneumonitis/interstitial lung disease requiring corticosteroids * Unmanageable ascites * Prior treatment with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway inhibitors may be permitted in certain study cohorts and excluded in others, as specified by the study protocol. * Renal impairment * Hepatic dysfunction * Hematologic abnormalities * Uncontrolled diabetes * Cardiac abnormalities * Active or history of clinically significant gastrointestinal (GI) or inflammatory GI disease * Other unacceptable abnormalities or prohibited therapies as defined by protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (Dose Escalation): Number of participants with Dose-Limiting Toxicities (DLT) | Baseline up to 28 days | Any adverse events that are attributable to one, the other, or both study treatments, occurring in the DLT observation period are considered DLTs, excluding toxicities clearly due to underlying disease or extraneous causes. |
| Part 1 (Dose Escalation): Incidence of Adverse Events (AEs) | From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first | An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. |
| Part 1 (Dose Escalation): Number of participants with laboratory abnormalities | From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first | Number of participants with laboratory test abnormalities. |
| Part 2 (Dose Expansion): Objective Response Rate (ORR) | Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years) | ORR defined as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Objective Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years) | ORR is defined as the percentage of participants in the analysis population having a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST v1.1. |
| Part 1 & Part 2: Disease Control Rate (DCR) as per RECIST v1.1 | Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years) | DCR is defined as the proportion of participants with CR or PR with confirmation, or Stable Disease (SD) per RECIST version 1.1. |
| Part 1 & Part 2: Clinical Benefit Rate (CBR) as per RECIST v1.1 | Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years) | CBR is defined as the percentage of participants with a best overall response of CR or PR at any time before Progressive Disease (PD), or non-CR/non-PD or SD for at least 24 weeks from start date of treatment and prior to PD, relative to the appropriate analysis set. |
| Part 1 & Part 2: Duration of Response (DOR) as per RECIST v1.1 | Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years) | DOR is defined as the time from first documentation of CR or PR to date of first documentation of PD or death due to any cause. |
| Part 1 & Part 2: Progression-Free Survival (PFS) as per RECIST v1.1 | Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years) | PFS is defined as time from start date of treatment to the date of first documentation of PD or death due to any cause. |
| Part 1 & Part 2: Time to Response (TTR) as per RECIST v1.1 | Baseline and every 8 to 12 weeks through time of confirmed disease progression, death, unacceptable toxicity, or through study completion (approximately 2 years) | TTR is defined as the time from start date of treatment to first documentation of CR or PR. |
| Part 1: Maximum Observed Serum Concentration (Cmax) & Trough Concentration (Ctrough) | Baseline through end of Cycle 1 (each cycle is 28 days) | Evaluate the single and multiple dose pharmacokinetic (s) (PK) of PF-08165784 as monotherapy, or in combination with other anti-tumor agents. |
| Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax) | Baseline through end of Cycle 1 (each cycle is 28 days) | Evaluate the single and multiple dose PK of PF-08165784 as monotherapy, or in combination with other anti-tumor agents. |
| Part 1: Area Under the Curve (AUC) from Time Zero to Last Quantifiable Concentration (AUClast) | Baseline through end of Cycle 1 (each cycle is 28 days) | Evaluate the single and multiple dose PK of PF-08165784 as monotherapy, or in combination with other anti-tumor agents. |
| Part 1: Effect of Food on Cmax | Baseline through end of Cycle 1 (each cycle is 28 days) | Evaluate the effect of food on Cmax of PF-08165784 as monotherapy |
| Part 1: Effect of Food on Tmax | Baseline through end of Cycle 1 (each cycle is 28 days) | Evaluate the effect of food on Tmax of PF-08165784 as monotherapy |
| Part 1: Effect of Food on AUClast | Baseline through end of Cycle 1 (each cycle is 28 days) | Evaluate the effect of food on AUClast of PF-08165784 as monotherapy |
| Part 2 (Dose Expansion): Number of participants with laboratory abnormalities | From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first | Number of participants with laboratory test abnormalities. |
| Part 2 (Dose Expansion): Incidence of Adverse Events (AEs) | From start of treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first | An adverse event (AE) was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship to it. |
| Part 2 (Dose Expansion): Pre- and post-dose concentrations of PF-08165784 | Baseline through end of Cycle 1 (each cycle is 28 days) | Evaluate the pre- and post-dose concentrations of PF-08165784 |
| Part 2: Overall Survival (OS) | Up to approximately 2 years | OS is defined as time from from start date of treatment to the date of death due to any cause |
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed