Clinical trial NCT00557856: A First In Patient, Study Of Investigational Drug PF-03446962 In Patients With Advanced Solid Tumors
Official title: A Phase 1 Pharmacokinetic And Pharmacodynamic Study Of Pf-03446962 In Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Solid Tumors Transforming Growth Factor Beta Activin Receptor-like Kinase 1
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-11-14
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the safety and effectiveness of PF-03446962 when given as a single agent. Tumors require new blood vessels to support their ability to grow and to spread (metastasize). New treatments aimed at preventing these blood vessels have the ability to improve the clinical management of cancer.


Eligibility criteria: Inclusion Criteria:

* Advanced measurable or non-measurable solid tumors
* Adequate bone marrow function
* Adequate liver function
* Adequate renal function
* Be able and willing to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures

Exclusion Criteria:

* Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of first dose of study medication
* Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, hemoptysis or melena in the past 6 months
* Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus; or any other active thromboembolic event
* QTc prolongation defined as QTc \>450 msec
* Patients with known brain metastasis
* Patients with peritoneal carcinosis at risk of bleeding
* Major surgical procedure within 4 weeks of treatment
* Pregnancy or breastfeeding

Primary outcomes:
measure: Maximum Tolerated Dose (MTD): Part 1
timeFrame: Baseline up to 42 days after the start of each increased treatment dose
measure: Recommended Phase 2 Dose (RP2D): Part 1
timeFrame: Baseline up to 42 days after the start of each increased treatment dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs): Part 1 and Part 2
timeFrame: Cycle 1 of Day 1 up to 28 days after the last dose of treatment
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity: Part 1 and Part 2
timeFrame: Cycle 1 of Day 1 up to 28 days after the last dose of treatment
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Seriousness: Part 1 and Part 2
timeFrame: Cycle 1 of Day 1 up to 28 days after the last dose of treatment
measure: Time to Treatment-Emergent Adverse Events (AEs): Part 1 and Part 2
timeFrame: Cycle 1 of Day 1 up to 28 days after the last dose of treatment
measure: Number of Participants With Laboratory Abnormalities: Part 1 and Part 2
timeFrame: Cycle 1 of Day 1 up to 28 days after the last dose of treatment
measure: Percentage of Participants With Objective Response: Part 1 and Part 2
timeFrame: Baseline then 6 weeks after Cycle 1 of Day1 thereafter every 6 weeks up to Day 490
measure: Percentage of Participants With Disease Control: Part 2
timeFrame: Baseline then 6 weeks after Cycle 1 of Day1 thereafter every 6 weeks up to Day 490
measure: Time To Progression (TTP): Part 2
timeFrame: Baseline then 6 weeks after Cycle 1 of Day1 thereafter every 6 weeks up to Day 490
measure: Volume of Distribution: Part 1 and Part 2
timeFrame: 0 hr (pre-dose),0.5,1,1.5,2,5,10,24 hr post-dose on Day (D) 1,3,5,8,11,15,22 of Cycle (C) 1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to cycle 12, 28 days after last dose for dose (up to 3 months after last dose for >=2 mg/kg arms)
Other outcomes:
measure: Maximum Observed Serum Concentration (Cmax): Part 1 and Part 2
timeFrame: 0 hr (pre-dose),0.5,1,1.5,2,5,10,24 hr post-dose on Day (D) 1,3,5,8,11,15,22 of Cycle (C) 1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to cycle 12, 28 days after last dose for dose (up to 3 months after last dose for >=2 mg/kg arms)
measure: Minimum Observed Serum Trough Concentration (Cmin): Part 1 and Part 2
timeFrame: 0 hr (pre dose), 1 hr post-dose C1D1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to C12
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-03446962: Part 1 and Part 2
timeFrame: 0 hr (pre-dose),0.5,1,1.5,2,5,10,24 hr post-dose on Day (D) 1,3,5,8,11,15,22 of Cycle (C) 1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to cycle 12, 28 days after last dose for dose (up to 3 months after last dose for >=2 mg/kg arms)
measure: Area Under the Curve From Time Zero to Day 28 [AUC (0-28)]: Part 1 and Part 2
timeFrame: 0 hr (pre-dose),0.5,1,1.5,2,5,10,24 hr post-dose on Day (D) 1,3,5,8,11,15,22 of Cycle (C) 1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to cycle 12, 28 days after last dose for dose (up to 3 months after last dose for >=2 mg/kg arms)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): Part 1 and Part 2
timeFrame: 0 hr (pre-dose),0.5,1,1.5,2,5,10,24 hr post-dose on Day (D) 1,3,5,8,11,15,22 of Cycle (C) 1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to cycle 12, 28 days after last dose for dose (up to 3 months after last dose for >=2 mg/kg arms)
measure: Systemic Clearance(CL): Part 1 and Part 2
timeFrame: 0 hr (pre-dose),0.5,1,1.5,2,5,10,24 hr post-dose on Day (D) 1,3,5,8,11,15,22 of Cycle (C) 1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to cycle 12, 28 days after last dose for dose (up to 3 months after last dose for >=2 mg/kg arms)
measure: Plasma Decay Half-Life (t1/2): Part 1 and Part 2
timeFrame: 0 hr (pre-dose),0.5,1,1.5,2,5,10,24 hr post-dose on Day (D) 1,3,5,8,11,15,22 of Cycle (C) 1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to cycle 12, 28 days after last dose for dose (up to 3 months after last dose for >=2 mg/kg arms)
measure: Human Anti - Human Antibody (HAHA) Concentration: Part 1 and Part 2
timeFrame: Baseline up to 3 months after last dose
measure: Soluble Protein Biomarker [Angiopoietin-2 (Ang-2), Bone Morphogenetic Protein-9 (BMP-9), Chemokine (C-C Motif) Ligand 2 (CCL2)]: Part 1 and Part 2
timeFrame: Baseline (pre-dose of C1D1), C1D1 6 hours post dosing, C1D22, C2D1, C3D1 and end of treatment (Day 490)
measure: Soluble Protein Biomarker [Cluster of Differentiation 106 (CD106), Cluster of Differentiation 54 (CD54), Endoglin]: Part 1 and Part 2
timeFrame: Baseline (pre-dose of C1D1), C1D1 6 hours post dosing, C1D22, C2D1, C3D1 and end of treatment (Day 490)
measure: Soluble Protein Biomarker [Placental Growth Factor (PLGF), Transforming Growth Beta 1 (TGFB1), Vascular Endothelial Growth Factor A (VEGF-A)]: Part 1 and Part 2
timeFrame: Baseline (pre-dose of C1D1), C1D1 6 hours post dosing, C1D22, C2D1, C3D1 and end of treatment (Day 490)
measure: Soluble Protein Biomarker [Vascular Endothelial Growth Factor C (VEGF-C), Vascular Endothelial Growth Factor-d (VEGF-d), Vascular Endothelial Growth Factor Receptor Type 1 (VEGFR1)]: Part 1 and Part 2
timeFrame: Baseline (pre-dose of C1D1), C1D1 6 hours post dosing, C1D22, C2D1, C3D1 and end of treatment (Day 490)
measure: Soluble Protein Biomarker [Vascular Endothelial Growth Factor Receptor Type 2 (VEGFR2), Vascular Endothelial Growth Factor Receptor Type 3 (VEGFR3)]: Part 1 and Part 2
timeFrame: Baseline (pre-dose of C1D1), C1D1 6 hours post dosing, C1D22, C2D1, C3D1 and end of treatment (Day 490)
measure: Circulating Endothelial Cells (CEC)and Circulating Endothelial Progenitors (CEP): Part 1 and Part 2
timeFrame: Baseline (pre-dose of C1D1), C1D1 6 hours post dosing, C1D22, C2D1, C3D1 and end of treatment (Day 490)
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Milano
country: Italy
facility: S.C Diagnostica Radiologica 2
city: Milano
country: Italy
facility: S.C. Chirurgia Generale Indirizzo Oncologico 1 (epato-gastro-pancreatica)
city: Milano
country: Italy
facility: S.C. Medicina Oncologica I, Fondazione IRCCS Istituto Nazionale Tumori
city: Milano
country: Italy
facility: Dipartimento di Medicina
city: Rozzano (MI)
country: Italy
facility: UO di Oncologia ed Ematologia, Istituto Clinico Humanitas-Humanitas Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital / Department of Internal Medicine
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Simonelli M, Zucali P, Santoro A, Thomas MB, de Braud FG, Borghaei H, Berlin J, Denlinger CS, Noberasco C, Rimassa L, Kim TY, English PA, Abbattista A, Gallo Stampino C, Carpentieri M, Williams JA. Phase I study of PF-03446962, a fully human monoclonal antibody against activin receptor-like kinase-1, in patients with hepatocellular carcinoma. Ann Oncol. 2016 Sep;27(9):1782-7. doi: 10.1093/annonc/mdw240. Epub 2016 Jun 20.
citation: Goff LW, Cohen RB, Berlin JD, de Braud FG, Lyshchik A, Noberasco C, Bertolini F, Carpentieri M, Stampino CG, Abbattista A, Wang E, Borghaei H. A Phase I Study of the Anti-Activin Receptor-Like Kinase 1 (ALK-1) Monoclonal Antibody PF-03446962 in Patients with Advanced Solid Tumors. Clin Cancer Res. 2016 May 1;22(9):2146-54. doi: 10.1158/1078-0432.CCR-15-1622. Epub 2015 Dec 11.