Safety Study of Regorafenib With PF-03446962 to Treat Colorectal Cancer

NCT02116894 | Completed Phase 1 DMC

• 1 other identifier: Pro00051541
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this open-label phase Ib trial is to determine the maximum tolerated dose and the recommended phase II dose for the combination of PF-03446962 plus regorafenib in patients with metastatic colorectal cancer. The secondary objectives are to describe the safety and tolerablility, and to describe the clinical activity of PF-03446962 plus regorafenib in terms of response rate and progression free survival

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; PF-03446962; regorafenib

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose (RPTD) for the combination of PF-03446962 plus regorafenib

  RPTD for the study will be determined at the completion of Phase I dose escalation cohort; estimated as 1 year

Secondary Outcomes (3)

• To evaluate the safety and tolerability of PF 03446962 administered in combination with regorafenib

  Continuous, every 4 weeks minimum until end of study estimated at 4 years

• Response rate of PF 03446962 plus regorafenib

  approximately every 8 weeks and/or restaging

• Progression free survival associated with PF 03446962 plus with regorafenib

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Study Arms (1)

PF-03446962 plus regorafenib

EXPERIMENTAL

Biological: PF-03446962; Drug: Regorafenib

Interventions

PF-03446962 BIOLOGICAL

PF-03446962 will be an investigational formulation supplied by Pfizer . PF-03446962 injection, 10 mg/mL is presented as a sterile solution for IV administration in a formulation consisting of precedented excipients. We will be administering PF-03446962 intravenously at a starting dose of 4.5 mg/kg and escalating to up to 7 mg/kg.

PF-03446962 plus regorafenib

Regorafenib DRUG

We will be administering regorafenib on-label for the indication of metastatic colorectal cancer. The indicated dose is 160 mg once daily for the first 21 days of a 28 day cycle. We will start at a regorafenib dose of 120 mg in the combination therapy, but may increase to 160 mg during dose escalation.

PF-03446962 plus regorafenib

Eligibility Criteria

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

You may qualify if:

• Histologically and/or cytologically confirmed and radiographically evaluable refractory metastatic colorectal adenocarcinoma for which regorafenib would be considered a therapeutic option.
• Disease must be measurable by RECIST 1.1 criteria (see Appendix 1).
• Age ≥ 18 years.
• ECOG 0 or 1.
• Life expectancy of at least 3 months.
• Adequate bone marrow function as shown by:
• ANC ≥ 1.5 x 109
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL; Erythropoietin and transfusion support is permitted provided treatments are not required more than every 8 weeks. Hemoglobin must be stable above or equal to 9 g/dL for at least 2 weeks prior to day 1of study drug without blood transfusion to maintain hemoglobin level.
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5x ULN
• PT/PTT/INR ≤ 1.5x ULN
• ALT and AST ≤ 2.5x ULN
• Adequate renal function: creatinine clearance (estimated) ≥ 50 cc/min by Cockroft Gault or 24 hour urine (see Appendix 6).
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days from day 1 of study drug; both men and women must be willing to use two methods of contraception, one of them being a barrier method during the study and for 6 months after last study drug administration.

You may not qualify if:

• Prior regorafenib use with disease progression (expanded cohort only).
• Prior failure to tolerate regorafenib at 120 mg/day.
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 28 days from day 1 of study drug (including investigational agents, chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patients who:
• Have had a major surgery or significant traumatic injury within 4 weeks from day 1 of study drug,
• Have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or
• Are anticipated to require major surgery during the course of the study.
• Patients who have exhibited hypersensitivity reactions to regorafenib and/or a structural compound, biological agent, or formulation (eg sorafenib).
• Grade 3-4 AE associated with prior anti-VEGF therapy. Grade 3 hypertension that was readily managed will be permitted.
• History of grade 3 or higher hypersensitivity reactions/anaphylaxis attributed to humanized and/or chimeric monoclonal antibodies or other such proteins. Hypersensitivity reactions that are clearly related to cetuximab may be permitted at the discretion of the principal investigator.
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent with the following exceptions:
• Intermittent steroids (not to exceed 4 mg every day) may be used on an as-needed basis (e.g. treatment for chemotherapy-related nausea, anorexia and fatigue.)
• Patients on physiologic replacement doses of steroids due to adrenal insufficiency for any reason may remain on these medications.
• Topical, inhaled or intra-articular corticosteroids
• Active brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Treated, asymptomatic metastases are permitted provided the patient has been off steroids for at least 1 month prior to day 1 of study drug.

Sponsors & Collaborators

• Duke University: lead
• Pfizer: collaborator

Study Sites (1)

Duke Cancer Center, Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

ascrinvacumab; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Herbert Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 17, 2014
• Study Start: August 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 14, 2019

Record last verified: 2019-03

Locations

US (1)