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Colorectal CancerPhase 1REGAL-1NCT02116894

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

A Phase 1 study testing PF-03446962 and Regorafenib in people with Colorectal Cancer, run by Duke University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
PF-03446962 and Regorafenib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
Aug 2014to May 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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).

Who cannot join

  • 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
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  • 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.
  • Poorly controlled hypertension [defined as systolic blood pressure (SBP of >140 mmHg or diastolic blood pressure (DBP) of >90 mmHg] NOTE: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure. The mean SBP/DBP ratio must be <140/90 mmHg in order for a subject to be eligible for the study.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of oral medications (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
  • Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1 of study drug
  • History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) or other significant spontaneous bleeding event within 1 month prior to day 1 of study drug or at any time on a prior VEGF inhibitor.
  • History of abdominal fistula or gastrointestinal perforation at any point within 6 months prior to day 1 of study drug, unless surgically repaired.
  • Active peptic ulcer disease, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation or gastrointestinal bleeding.
  • Use or need for full dose anticoagulation other than low molecular weight heparin and Factor Xa inhibitors (e.g. Lovenox, Fondaparinux) and no other bleeding risk.
  • Serious, non-healing wound, active ulcer, or untreated bone fracture as judged by treating physician.
  • Active bleeding diathesis.
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
  • Known history of HIV or Hepatitis B or C seropositivity.
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Two acceptable forms of contraceptives must be continued throughout the trial by either sex and for 2 months (60 days) following last dose of either drug. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to day 1 of study drug).
  • Concomitant use of CYP3A4 strong inducers and strong inhibitors. (See Appendix 7).
  • Corrected QTc interval > 500 msec. If QTc interval is > 500 msec, then 2 additional ECGs should be obtained over a brief period of time (e.g., within 15-20 minutes) to confirm the abnormality. The average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the subject will be excluded from the study. The same method of QTc determination must be used throughout the subject's participation in the trial.
  • History of Osler-Weber-Rendu syndrome or Hereditary Hemorrhagic Telangiectasia
  • Patients unwilling to or unable to comply with the protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke Cancer Center, Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: Phase Ib Study of the Combination Regorafenib With PF-03446962 in Patients With Refractory Metastatic Colorectal Cancer (REGAL-1 Trial)

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

Being tested
PF-03446962, Regorafenib
Keywords
Colorectal cancer, PF-03446962, regorafenib
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-03446962Biological

    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.

  • RegorafenibDrug

    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.

Study groups in NCT02116894
Study groupRoleWhat they receive
PF-03446962 plus regorafenibExperimentalNot described
Receives: Biological: PF-03446962; Drug: Regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

Secondary outcomes (3)

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

    Adverse events will be recorded

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

  2. Response rate of PF 03446962 plus regorafenib

    Response is assessed at restaging, approximately every 8 weeks, assessed for an average of 6 months

    Measured: approximately every 8 weeks and/or restaging

  3. Progression free survival associated with PF 03446962 plus with regorafenib

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2014 (estimated)
  2. Study startAug 2014
  3. Primary completionFeb 2016
  4. Study completionMay 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02116894
Sponsor's protocol ID
Pro00051541
Acronym
REGAL-1
Status last verified
Mar 2019
First submitted
8 Apr 2014
Last updated
14 Mar 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-03446962 and Regorafenib in people with Colorectal Cancer, run by Duke University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase II dose (RPTD) for the combination of PF-03446962 plus regorafenib (time frame: RPTD for the study will be determined at the completion of Phase I dose escalation cohort; estimated as 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02116894.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2019.

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REGAL-1 Clinical Trial NCT02116894 | AzTrials