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

Completed · Phase 1

Conditions studied: Colorectal Cancer

In brief

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

Key facts

Study ID

NCT02116894

Run by

Duke University

People needed

11

Starts

2014-08-01

Expected to finish

2016-05-01

Last updated by the study team

2019-03-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Signed informed consent.
• Presence of an archived tumor sample (no size requirements).

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.
• Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or O2 saturation <90% by pulse oximetry after a 2 minute walk or in the opinion of the investigator any physiological state likely to cause systemic or regional hypoxemia.
• Presence of poorly controlled atrial fibrillation (ventricular heart rate >100 bpm)
• Previous history of CVA, TIA, angina pectoris, acute MI or history of recent re-perfusion procedures (e.g. PTCA), pulmonary embolus or untreated deep vein thrombosis (DVT) within 6 months from day 1 of study drug. NOTE: Subjects with recent DVT who have been therapeutically anti-coagulated for at least 6 weeks are eligible.
• Known significant or active CAD or PVD or CVD defined as abnormal stress test, symptoms, or requiring medication for the prevention of symptoms.
• Congestive heart failure (New York Heart Association (NYHA classification, see Appendix 4 functional classification III-IV).
• Proteinuria at screening demonstrated by urine analysis (UA) > 1+ and 24 hour urine protein ≥ 1 gram/24 hours.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study as so judged by the treating physician. Examples include but are not limited to:
• Severely impaired lung function (e.g. use of home O2, history of Idiopathic Lung Disease (ILD), any evidence of ILD on scan.
• Active (acute or chronic) severe infections requiring treatment with I.V. antibiotics.
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.

Where it is running

• Duke Cancer Center, Duke University Medical Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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