A First In Patient, Study Of Investigational Drug PF-03446962 In Patients With Advanced Solid Tumors

NCT00557856 | Completed Phase 1 Results

• 2 other identifiers: A84710012007-001422-27
• Study Type: interventional
• Target: 70
• Locations: 3 countries
• Sites: 10

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.

Conditions

Advanced Solid Tumors

Keywords

Solid Tumors Transforming Growth Factor Beta Activin Receptor-like Kinase 1

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD): Part 1

  MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced DLT and at least 2 out of 3/6 participants in the next higher dose. DLT was defined as any of the following events occurring during the first 42 days of study drug: any grade greater than or equal to 3 hematologic and non-hematologic toxicity, all non-disease-related adverse events (AEs).

  Baseline up to 42 days after the start of each increased treatment dose

• Recommended Phase 2 Dose (RP2D): Part 1

  RP2D was defined as the lower dose level to MTD based on the safety profile.

  Baseline up to 42 days after the start of each increased treatment dose

Secondary Outcomes (9)

• Number of Participants With Treatment-Emergent Adverse Events (AEs): Part 1 and Part 2

  Cycle 1 of Day 1 up to 28 days after the last dose of treatment

• Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity: Part 1 and Part 2

  Cycle 1 of Day 1 up to 28 days after the last dose of treatment

• Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Seriousness: Part 1 and Part 2

  Cycle 1 of Day 1 up to 28 days after the last dose of treatment

• Time to Treatment-Emergent Adverse Events (AEs): Part 1 and Part 2

  Cycle 1 of Day 1 up to 28 days after the last dose of treatment

• Number of Participants With Laboratory Abnormalities: Part 1 and Part 2

  Cycle 1 of Day 1 up to 28 days after the last dose of treatment

Other Outcomes (14)

• Maximum Observed Serum Concentration (Cmax): Part 1 and Part 2

  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)

• Minimum Observed Serum Trough Concentration (Cmin): Part 1 and Part 2

  0 hr (pre dose), 1 hr post-dose C1D1, 0 hr,1 hr post-dose on Day 1 of subsequent cycles up to C12

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-03446962: Part 1 and Part 2

  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)

Study Arms (1)

1

EXPERIMENTAL

Drug: PF-03446962

Interventions

PF-03446962 DRUG

To determine the maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of PF-03446962 administered in patients with advanced solid tumors.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (10)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37212-3505, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

S.C Diagnostica Radiologica 2

Milan, 20133, Italy

Location

S.C. Chirurgia Generale Indirizzo Oncologico 1 (epato-gastro-pancreatica)

Milan, 20133, Italy

Location

S.C. Medicina Oncologica I, Fondazione IRCCS Istituto Nazionale Tumori

Milan, 20133, Italy

Location

Dipartimento di Medicina

Milan, 20141, Italy

Location

UO di Oncologia ed Ematologia, Istituto Clinico Humanitas-Humanitas Cancer Center

Rozzano (MI), 20089, Italy

Location

Seoul National University Hospital / Department of Internal Medicine

Seoul, 110-744, South Korea

Location

Related Publications (2)

• 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.

  PMID: 27329247 DERIVED

• 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.

  PMID: 26655846 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

ascrinvacumab

Limitations and Caveats

Results for tumor vascular function adopting dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) was not reported as per change in planned analysis.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2007
• First Posted: November 14, 2007
• Study Start: November 1, 2007
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: October 19, 2015
• Results First Posted: August 13, 2015

Record last verified: 2015-09

Locations

IT (5); US (4); KR (1)