A Study Of Poly (ADP-Ribose) Polymerase Inhibitor PF-01367338 In Combination With Several Chemotherapeutic Regimens

Study Overview
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Brief Summary
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Dose escalation phase 1 study of PARP inhibitor PF-01367338 in combination with chemotherapy in adult patients with advanced solid tumors

Official Title
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A Parallel Arms Phase 1 Safety, Pharmacokinetic And Pharmacodynamic Study Of The Intravenous Poly (ADP-Ribose) Polymerase (PARP) Inhibitor PF-01367338 (AG-014699) In Combination With Several Chemotherapeutic Regimens In Adult Patients With Advanced Solid Tumor

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: PF-01367338
* Drug: Carboplatin
* Drug: PF-01367338
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed solid tumors, Eastern Cooperative Oncology Group (ECOG) 0 or 1 Patients with acceptable renal, hepatic, and bone marrow function Exclusion Criteria: Symptomatic and/or unstable brain metastases, Any cancer treatment within 4 weeks from study entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM A<br>Carboplatin plus PF-01367338 | Drug: PF-01367338<br>* Increasing doses of single lead-in (Day -10) intravenous and daily oral PF-01367338 administered from Day 1 to Day 14 every 3-week cycle<br>Drug: Carboplatin<br>* Standard doses of intravenous Carboplatin administered every 3 weeks<br>|
| Experimental: ARM A EXPANSION<br>Carboplatin plus PF-01367338 | Drug: PF-01367338<br>* RP2 doses of oral PF-01367338 administered daily from Day 1 to Day 14 every 3-week cycle<br>Drug: Carboplatin<br>* Standard doses of intravenous Carboplatin administered every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of escalating doses of PF-01367338 in combination with chemotherapy (as defined by first-cycle DLTs) | Dose-limiting toxicities and adverse events | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics and pharmacodynamics of escalating doses of PF-01367338 in combination with several chemotherapeutic regimens | Time to attain maximum plasma concentration [Tmax] | 18 months | 
| Pharmacokinetics and pharmacodynamics of escalating doses of PF-01367338 in combination with several chemotherapeutic regimens | maximum plasma concentration (CMax) | 18 months | 
| Pharmacokinetics and pharmacodynamics of escalating doses of PF-01367338 in combination with several chemotherapeutic regimens | area under plasma concentration curve (AUC) | 18 months | 
| Pharmacokinetics and pharmacodynamics of escalating doses of PF-01367338 in combination with several chemotherapeutic regimens | apparent terminal half-life (t1/2) | 18 months | 
| Pharmacokinetics and pharmacodynamics of escalating doses of PF-01367338 in combination with several chemotherapeutic regimens | rucaparib oral bioavailability | 18 months | 
| PARP activity and expression in peripheral blood lymphocytes (PBL) | % PARP activity | 18 months | 
| Determination of food effect on oral PF-01367338 pharmacokinetics | fasted and fed parameters area under the plasma concentration-time curve from time 0 to the last recorded observation [AUClast] | 18 month | 
| Determination of food effect on oral PF-01367338 pharmacokinetics | fasted and fed maximum plasma concentration (Cmax) | 18 month | 
| Determination of effect of PF-013567338 administration on QTc prolongation test | electrocardiogram[ecg], QTcF, QTcB | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose finding PARPi Chemotherapy