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Trifluridine/Tipiracil and Talazoparib for the Treatment of Patients With Locally Advanced or Metastatic Colorectal or Gastroesophageal Cancer

ConditionsAdvanced Malignant Solid NeoplasmClinical Stage III Gastroesophageal Junction AdenocarcinomaClinical Stage IV Gastroesophageal Junction AdenocarcinomaClinical Stage IVA Gastroesophageal Junction AdenocarcinomaClinical Stage IVB Gastroesophageal Junction Adenocarcinoma ALocally Advanced Colorectal CarcinomaLocally Advanced Gastroesophageal Junction AdenocarcinomaMetastatic Colorectal AdenocarcinomaMetastatic Gastroesophageal Junction AdenocarcinomaPathologic Stage III Gastroesophageal Junction AdenocarcinomaPathologic Stage IIIA Gastroesophageal Junction AdenocarcinomaPathologic Stage IIIB Gastroesophageal Junction AdenocarcinomaPathologic Stage IV Gastroesophageal Junction AdenocarcinomaPathologic Stage IVA Gastroesophageal Junction AdenocarcinomaPathologic Stage IVB Gastroesophageal Junction AdenocarcinomaPostneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8Stage III Colorectal Cancer AJCC v8Stage IIIA Colorectal Cancer AJCC v8Stage IIIB Colorectal Cancer AJCC v8Stage IIIC Colorectal Cancer AJCC v8Stage IV Colorectal Cancer AJCC v8Stage IVA Colorectal Cancer AJCC v8Stage IVB Colorectal Cancer AJCC v8Stage IVC Colorectal Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorRoswell Park Cancer Institute

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Trifluridine and Tipiracil Hydrochloride

    Drug

    Given PO

  • Talazoparib Tosylate

    Drug

    Given PO

Treatment groups

45 Participants
are divided into 1 treatment group
Group A: Treatment ArmExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Incidence of Adverse Events

All adverse events will be evaluated using Common Terminology Criteria for All Adverse Events (CTCAE) version (v.) 5.

Time frame
after each cycle of treatment ( 1 cycle = 14 days)
2

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

Time frame
Up to 14 days

Secondary outcomes

1

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

Time frame
Day -13 post dose
2

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

Time frame
day -14 pre dose
3

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

Time frame
day -14 post dose
4

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

Time frame
day -13 pre dose

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Roswell Park Cancer Institute

Lead sponsor

Pfizer

Collaborator

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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