Phase II Pilot Study of FOLFOXIRI Plus Panitumumab in Metastatic RAS Wild-type, Left-sided Colorectal Cancer
FOLFOXIRI Plus Panitumumab in Metastatic RAS Wild-type, Left-sided Colorectal Cancer
Sponsors
Source
Criterium, Inc.
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Is Us Export
No
Brief Summary
This is a phase II, open-label, non-randomized study in subjects with histologically
confirmed diagnosis of left-sided RAS WT advanced adenocarcinoma of the colon or rectum who
have not received prior systemic therapy for metastatic disease.
Overall Status
Not yet recruiting
Start Date
2019-12-01
Completion Date
2021-12-01
Primary Completion Date
2021-09-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Efficacy/objective response rate |
Through progression of disease, on average 6 months. |
Secondary Outcome
Measure |
Time Frame |
Evaluating progression free survival (PFS) |
Through progression of disease, on average 6 months. |
Evaluating overall survival (OS) |
Through progression of disease, on average 6 months. |
Evaluating toxicity of this regimen |
Through progression of disease, on average 6 months. |
Evaluating radiographic tumor regression |
Through progression of disease, on average 6 months. |
Evaluating for the velocity of tumor response to this regimen |
Patients will be followed until death or 5 years |
Enrollment
35
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
2 week cycles
Arm Group Label
Active
Other Name
Irinotecan
Leucovorin
Panitumumab
Eligibility
Criteria
Inclusion Criteria:
1. Subjects must have signed an approved informed consent.
2. Histologically confirmed diagnosis of advanced adenocarcinoma of the colon or rectum.
3. No previous systemic chemotherapy for metastatic disease
- Subjects who have had prior adjuvant chemotherapy for non-metastatic disease are
eligible if more than six months have elapsed after completing therapy
- Subjects treated with adjuvant chemotherapy who relapse within six months after
completion will not be eligible.
4. Bidimensionally measurable disease as defined in Section 3.3.1.
5. RAS wild-type tested in
- KRAS exon 2 (codons 12/13)
- KRAS exon 3 (codons 59/61)
- KRAS exon 4 (codons 117/146)
- NRAS exon 2 (codons 12/13)
- NRAS exon 3 (codons 59/61)
- NRAS exon 4 (codons 117/146)
6. ECOG Performance Status 0-1 (Appendix 1).
7. Recovery in full, from any previous surgical procedure.
8. Subjects >=18 years of age. Women of childbearing potential (WOCBP) must be using an
adequate method of contraception to avoid pregnancy throughout the study and for up to
6 months after the study in such a manner that the risk of pregnancy is minimized.
WOCBP include any female who has experienced menarche and who has not undergone
successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral
oophorectomy) or is not postmenopausal.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
or equivalent units of HCG) within 72 hours prior to the start of study medication.
9. Creatinine clearance ≥ 50 ml/min or serum creatinine ≤ 1.5 x upper limit of normal.
10. Bilirubin ≤ 1.5 x upper limit of normal
11. AST, ALT ≤ 2.5 x upper limit of normal in absence of liver metastases, or ≤ 5 x upper
limit of normal in presence of liver metastases,
12. Albumin within normal institutional limits
13. Magnesium ≥ lower limit of normal; calcium ≥ lower limit of normal .
14. Absolute Neutrophil Count > 1500/mm3 and platelets > 100,000/mm3.
Exclusion Criteria:
1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for
the entire study period and for up to 6 months after the study. Subjects who are men
must also agree to use effective contraception.
2. Women who are pregnant or breastfeeding.
3. Women with a positive pregnancy test on enrollment or prior to study drug
administration.
4. Subjects with >grade 1 neuropathy except for loss of tendon reflex.
5. Any active or uncontrolled infection.
6. Clinically significant cardiovascular disease (myocardial infarction, unstable angina,
symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6
months before enrollment
7. Past or current history of malignancies except for the indication under this study and
curatively treated:
- Basal and squamous cell carcinoma of the skin
- In-situ carcinoma of the cervix
- Other malignant disease without recurrence after at least 3 years of follow-up
8. History or evidence upon physical examination of CNS disease unless adequately treated
(e.g. primary brain tumor, seizure not controlled with standard medical therapy, brain
metastases or history of stroke).
9. Clinically relevant interstitial lung disease (pneumonitis, pulmonary fibrosis,
evidence of interstitial lung disease on baseline chest CT scan)
10. Allogeneic transplantation requiring immunosuppressive therapy.
11. Severe non-healing wounds, ulcers or bone fractures.
12. Evidence of bleeding diathesis or coagulopathy.
13. Patients not receiving therapeutic anticoagulation must have an INR < 1.5 x ULN and
aPTT < 1.5 x ULN within 7 days prior to randomization. The use of full-dose
anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits
(according to the medical standard in the institution) and the patient has been on a
stable dose for anticoagulants for at least two weeks.
14. Concomitant therapy with certain anti-viral medicines (sorivudine and brivudine or
analogue compounds).
15. Major surgical procedure, open biopsy, nor significant traumatic injury within 28 days
prior to study treatment start, or anticipation of the need for major surgical
procedure during the course of the study except for surgery for colorectal cancer with
curative intent and central venous line placement for chemotherapy administration.
16. Subjects with known allergy to the study drugs or to any of its metabolites.
17. Known DPD deficiency.
18. Current or recent (within the 28 days prior to starting study treatment) treatment of
another investigational drug or participation in another investigational study.
19. Known grade III/IV allergic reaction against monoclonal antibodies.
20. Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions
should be discussed with the subject before registration in the trial.
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Howard Hochster, MD |
Principal Investigator |
Lead Site PI |
Overall Contact
Verification Date
2019-09-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Has Expanded Access
No
Condition Browse
Number Of Arms
1
Intervention Browse
Mesh Term
Oxaliplatin
Panitumumab
Arm Group
Arm Group Label
Active
Arm Group Type
Other
Description
This is an open label study single arm
Firstreceived Results Date
N/A
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Intervention Model
Single Group Assignment
Intervention Model Description
Multicenter open-label
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
September 24, 2019
Study First Submitted Qc
November 18, 2019
Study First Posted
November 19, 2019
Last Update Submitted
November 18, 2019
Last Update Submitted Qc
November 18, 2019
Last Update Posted
November 19, 2019
ClinicalTrials.gov processed this data on December 10, 2019
Conditions
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.