Combining trifluridine/tipiracil with talazoparib for advanced colorectal or gastroesophageal cancer
A Phase I Study of Trifluridine/ Tipiracil Plus the Poly (ADP) Ribose Polymerase Inhibitor Talazoparib in Advanced Cancers
This study is testing a new combination of two cancer drugs to see if they can safely help people with advanced colorectal or gastroesophageal cancer.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 45 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Roswell Park Cancer Institute Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Buffalo, New York) |
| Trial ID | NCT04511039 on ClinicalTrials.gov |
What this trial studies
This phase I trial evaluates the safety and optimal dosage of talazoparib when used alongside trifluridine/tipiracil in patients with locally advanced or metastatic colorectal or gastroesophageal cancer. The study aims to determine the maximum tolerated dose and recommended phase 2 dose of the drug combination. It also investigates the pharmacokinetics and pharmacodynamics of the treatment, as well as its preliminary effectiveness in inhibiting tumor growth. The approach focuses on leveraging the distinct mechanisms of action of both drugs to enhance treatment outcomes.
Who should consider this trial
Good fit: Ideal candidates include patients with histologically confirmed locally advanced or metastatic colorectal or gastroesophageal adenocarcinoma who have received at least one prior line of therapy.
Not a fit: Patients with early-stage cancer or those who have not received prior treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced colorectal or gastroesophageal cancer.
How similar studies have performed: Other studies have shown promise in combining targeted therapies with chemotherapy for similar cancer types, suggesting potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Histologically or cytologically confirmed CRC or EGC adenocarcinoma that is locally advanced or metastatic (Cohort A); histologically or cytologically confirmed p53mt/RASonc (Cohort B1) or p53mt/RASwt CRC (Cohort B2) that is locally advanced or metastatic. Patients with adenocarcinoma histology only are allowed to participate. * Has received at least one prior line of therapy with progression or intolerance * Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Life expectancy \>= 3 months by investigator assessment * Hemoglobin \>= 9 g/dL * Absolute neutrophil count \>= 1500/mm\^3 * Platelet count \>= 100,000/mm\^3 without transfusion or growth factor support * Creatinine \< 1.5 upper limit of normal (ULN) or creatinine clearance \> 60 mL/min * Total bilirubin \< 1.5 x ULN * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN or \< x 5 ULN in the presence of liver metastasis * Albumin \> 3 g/dL * Ability to swallow oral medications * Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: * Systemic antineoplastic therapy within 2 weeks prior to day -14 (Dose Escalation, Cohort A) or Cycle 1 day 1 (Dose Expansion, Cohorts B1 and B2) or within the past 6 weeks if this treatment is mitomycin C or nitrosourea * Radiotherapy within the past 2 weeks excluding palliative radiotherapy to painful bone lesions * Prior treatment with PARP inhibitor, FUDR or FTD/TPI * Any condition that in the investigator's opinion can limit absorption of FTD/TPI or talazoparib from the gastrointestinal (GI) tract * Gastrointestinal obstruction (without diversion) or perforation within 4 weeks from initiation of day -14 (Dose Escalation, Cohort A) or Cycle 1 Day 1 (Dose Expansion, Cohorts B1 and B2. * Refractory ascites (requiring weekly or more frequent paracentesis or permanent indwelling peritoneal catheter) * Untreated central nervous system (CNS) disease. Patients with leptomeningeal disease are ineligible but patients with treated, stable CNS metastasis for at least 4 weeks are allowed to participate * Significant cardiac disease defined as congestive heart failure stage III or IV (New York Heart Association \[NYHA\]), acute coronary event, cerebrovascular event, peripheral arterial embolic event, venous thromboembolic event (pulmonary embolism or lower extremity deep vein thrombosis), or ventricular arrhythmia within the past 3 months * Other malignancy requiring active therapy * Presence of toxicities from prior therapy of grade 2 or higher * Active infection requiring antibiotic therapy * Known human immunodeficiency virus (HIV) or hepatitis B infection or untreated hepatitis C infection. Patients with treated hepatitis C infection and undetectable viral load are allowed to participate * Any history of myelodysplastic syndrome, acute leukemia, or bone marrow transplant * Pregnant or nursing female participants * Unwilling or unable to follow protocol requirements * Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Where this trial is running
Buffalo, New York
- Roswell Park Cancer Institute — Buffalo, New York, United States (Recruiting)
Study contacts
- Principal investigator: Christos Fountzilas, MD — Roswell Park Cancer Institute
- Study coordinator: Sarah Chatley, BS
- Email: Sarah.Chatley@roswellpark.org
- Phone: 716-845-4846
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.