Advanced Malignant Solid NeoplasmPhase 1NCT04511039
Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer
A Phase 1 study testing Trifluridine and Tipiracil Hydrochloride and Talazoparib Tosylate in people with Advanced Malignant Solid Neoplasm and Clinical Stage III Gastroesophageal Junction Adenocarcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
This phase I trial investigates the side effects and best dose of talazoparib when given together with trifluridine/tipiracil for the treatment of patients with colorectal or gastroesophageal cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Solid Neoplasm, Clinical Stage III Gastroesophageal Junction Adenocarcinoma, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- Trifluridine and Tipiracil Hydrochloride and Talazoparib Tosylate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jun 2021to 1 Apr 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Christos Fountzilas, MD
About this study
Official title: A Phase I Study of Trifluridine/ Tipiracil Plus the Poly (ADP) Ribose Polymerase Inhibitor Talazoparib in Advanced Cancers
This phase I trial investigates the side effects and best dose of talazoparib when given together with trifluridine/tipiracil for the treatment of patients with colorectal or gastroesophageal cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Drugs used in the chemotherapy, such as trifluridine/tipiracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving talazoparib with trifluridine/ tipiracil may inhibit certain enzymes in the cells that are responsible for tumor cell growth.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of trifluridine and tipiracil hydrochloride (trifluridine/tipiracil [FTD/TPI]) in combination with talazoparib tosylate (talazoparib) in patients with advanced colorectal (CRC) or gastroesophageal (EGC) adenocarcinoma.
SECONDARY OBJECTIVES:
- To determine the pharmacokinetics (PK) and pharmacodynamic (PD) markers of activity.
II. To evaluate the preliminary antineoplastic efficacy of the combination.
- Conditions
- Advanced Malignant Solid Neoplasm, Clinical Stage III Gastroesophageal Junction Adenocarcinoma, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma, Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma, Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma A, Locally Advanced Colorectal Carcinoma
- Being tested
- Trifluridine and Tipiracil Hydrochloride, Talazoparib Tosylate
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trifluridine and Tipiracil HydrochlorideDrug
Also called 733030-01-8, Lonsurf, TAS 102,, Thymidine
Given PO
Talazoparib TosylateDrug
Also called Talzenna
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Patients receive trifluridine/tipiracil PO BID and talazoparib tosylate PO QD on days 1-5. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Trifluridine and Tipiracil Hydrochloride; Drug: Talazoparib Tosylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events
All adverse events will be evaluated using Common Terminology Criteria for All Adverse Events (CTCAE) version (v.) 5.
Measured: after each cycle of treatment ( 1 cycle = 14 days)
Maximum tolerated dose/ recommended phase II dose
Will utilize the keyboard design - a novel model- assisted dose-finding method to find the maximum tolerated dose
Measured: Up to 14 days
Secondary outcomes (10)
Plasma Concentration (Cmax)
The pharmacokinetic parameters between Trifluridine/Tipiracil and Talazoparib will be evaluated on Day -14: pre-dose, 0.5, 1, 2, 4, 6, 8 hours (hr) post-dose; day-13: 24 hr post-initial dose and day -13 pre-dose
Measured: Day -13 post dose
Plasma Concentration (Cmax)
The pharmacokinetic parameters between Trifluridine/Tipiracil and Talazoparib will be evaluated on Day -14: pre-dose, 0.5, 1, 2, 4, 6, 8 hours (hr) post-dose; day-13: 24 hr post-initial dose and day -13 pre-dose
Measured: day -14 pre dose
Plasma Concentration (Cmax)
The pharmacokinetic parameters between Trifluridine/Tipiracil and Talazoparib will be evaluated on Day -14: pre-dose, 0.5, 1, 2, 4, 6, 8 hours (hr) post-dose; day-13: 24 hr post-initial dose and day -13 pre-dose
Measured: day -14 post dose
Plasma Concentration (Cmax)
The pharmacokinetic parameters between Trifluridine/Tipiracil and Talazoparib will be evaluated on Day -14: pre-dose, 0.5, 1, 2, 4, 6, 8 hours (hr) post-dose; day-13: 24 hr post-initial dose and day -13 pre-dose
Measured: day -13 pre dose
Overall Response Rate (ORR)
Will be summarized using frequencies and relative frequencies.
Measured: Up to 3 years
CEA response rate (colorectal cancer patients)
ill be summarized using frequencies and relative frequencies. .
Measured: Up to 3 years
Progression Free Survival (PFS)
Will be summarized using standard Kaplan-Meier methods
Measured: From treatment until disease progression UP to 3 years
Overall Survival (OS)
Will be summarized using standard Kaplan-Meier methods
Measured: From treatment until death or up to 3 years
Progressive Disease Assessment (PD)
Measured: Up to 3 years
Number of subjects with DNA damage response
Tumor biopsies will be summarized by dose level and time-point using means and standard deviations.
Measured: Up to 28 days prior to first drug dose, on treatment and between cylce 1-day 8 and cycle 1 day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2020
- Study start8 Jun 2021
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Malignant Solid NeoplasmStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Christos Fountzilas, MD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04511039
- Sponsor's protocol ID
- I 650120
- Other IDs
- R37CA282430
- Status last verified
- Apr 2026
- First submitted
- 7 Aug 2020
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes