Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Colorectal Neoplasms
Conditions
Keywords
mCRC, metastatic disease, first-line, metastatic colorectal cancer, colon cancer
Brief summary
The purpose of this study is to learn more about a new medicine called PF-08634404, and how well it works in people with cancer of the colon or rectum (CRC)). The goal is to understand if the new study medicine, combined with chemotherapy that is approved for colorectal cancer, can help people whose cancer has spread or returned after treatments taken before. To join the study, participants must meet the following conditions: * Be 18 years or older. * Have colorectal cancer that has spread to other parts of your body. * Be in good enough health to receive study treatment. * Should not be pregnant before starting treatment. Participants will be randomized (like flipping a coin) to one of 2 different treatment arms. The first arm (Arm A) will include the new medicine PF-08634404 in combination with chemotherapy that is approved for colorectal cancer, and the second arm (Arm B) will include an approved medicine for colorectal cancer, called Bevacizumab, in combination with chemotherapy that is approved for this type of cancer. Participants and their doctors will not know which arm they are being assigned to. Participants will receive all the study medications through intravenous (IV) infusions, which means the medicine is given directly into a vein. The treatment will be given in cycles, and participants may continue receiving it if it is helping and they are not experiencing serious side effects. The medicine will be given at a clinical site, where trained medical staff will check participants during and after each treatment. * The study is expected to last approximately 33 months for each participant. * Participants will have regular visits to the study site for treatment, health checks, and tests. * After stopping treatment, participants will return for a final visit about 30 to37 days later to check their health and review any side effects. * Follow-up will continue every 12 weeks by phone or in person or by reviewing health records to check on health status and any new treatments.
Interventions
DRUGPF-08634404
Solution for infusion
BIOLOGICALBevacizumab
Injection for intravenous use
DRUGChemotherapy
Injection for intravenous use
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmed colorectal adenocarcinoma. * Evidence of Stage IV metastatic disease. * No prior systemic therapy for metastatic disease. * Eastern Cooperative Oncology Group performance status (ECOG) 0-1 * At least one measurable lesion according to RECIST 1.1 per Investigator assessment. * Adequate hepatic, liver, and renal function
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * Locally confirmed BRAF V600E mutation * Locally confirmed microsatellite instability (MSI)-high or DNA mismatch repair deficiency (dMMR) colorectal cancer * Participants with known active symptomatic CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression * Clinically significant risk of hemorrhage or fistula * Major surgery or severe trauma within 4 weeks prior to the first dose, or planned major surgery during the study * History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation * Any Grade ≥3 bleeding/hemorrhage events within 28 days of Cycle 1 Day 1, or prior history of clinically significant bleeding events * Clinically significant cardiovascular disease, or other comorbidities, within 6 months prior to first dose * Participants with active autoimmune diseases requiring systemic treatment within the past 2 years * Evidence of non-infectious or drug-induced interstitial lung disease (ILD) pneumonitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) | Approximately 4 years | Progression-free survival is defined as the time from the date of randomization to the date of the first documentation of objective progressive disease (PD) assessed by BICR per RECIST 1.1, or death due to any cause, whichever occurs first. |
| Overall survival (OS) | Approximately 4 years | Overall survival defined as the time from the date of randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS per RECIST 1.1 by investigator assessment | Approximately 4 years | Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of the first documentation of objective PD assessed by investigator per RECIST 1.1, or death due to any cause, whichever occurs first. |
| Objective Response Rate (ORR) by BICR | Approximately 4 years | The proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1. |
| Objective Response Rate (ORR) by investigator | Approximately 4 years | The proportion of participants who have a confirmed CR or PR, as best overall response assessed by investigator as per RECIST 1.1. |
| Duration of Response (DOR) by BICR | Approximately 4 years | The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by BICR assessment per RECIST 1.1, or death due to any cause, whichever occurs first. |
| DOR by investigator | Approximately 4 years | The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of the first documentation of PD as determined by Investigator per RECIST 1.1, or death due to any cause, whichever occurs first. |
| PFS2 (PFS after next-line therapy) by investigator | Approximately 4 years | PFS2 is defined as the time from the date of randomization to the date of second objective disease progression or death due to any cause, whichever occurs first. Second objective disease progression is PD after the start of subsequent anticancer therapy (excluding curative surgery) as assessed by the investigator. |
| Number of Participants with Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Through 90 days after the last study intervention; Approximately 4 years | — |
| Number of Participants With Clinical Laboratory Abnormalities | Through 90 days after the last study intervention; Approximately 4 years | — |
| Pharmacokinetics (PK): Serum concentration of PF-08634404 | Approximately 21 months | — |
| Immunogenicity: Incidence of positive Anti-Drug Antibody (ADA) | Approximately 21 months | To characterize the immunogenicity of PF-08634404 |
| Mean scores and Change from baseline in the global health status/quality of life (QoL) score on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Approximately 4 years | The EORTC QLQ-C30 is a questionnaire for quantitative measure of health-related quality of life pertinent to participants with a broad range of cancers who are participating in international clinical trials. |
| Mean score change from baseline in participant reported function and symptoms scales per EORTC QLQ-CR29 | Approximately 4 years | The EORTC QLQ-CR29 is a supplemental colorectal cancer-specific module with measures of symptoms associated with colorectal cancer. |
| Time to definitive deterioration (TTdD) in the global health status/QoL score on the EORTC QLQ-C30 | Approximately 4 years | TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery. |
| Time to definitive deterioration (TTdD) in participant reported function and symptoms per EORTC QLQ-CR29 | Approximately 4 years | TTdD is defined as the time from date of randomization to first onset of Patient Reported Outcome (PRO) deterioration without subsequent recovery. |
Countries
Australia, Japan, Puerto Rico, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed