SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial
Condition: Cancer; Colon Cancer; Colorectal Cancer; Metastatic Cancer; Rectal Cancer; Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Panitumumab; Bevacizumab; Leucovorin; Irinotecan; 5-Fluorouracil
Intervention description: 6mg/kg IV; Either 5mg/kg OR 10mg/kg IV; 400mg/m^2 IV (in the vein); 180mg/m^2 IV (in the vein); 400mg/m^2 bolus IV (in the vein) over 2-4 min, followed by 2400mg/m^2 continuous IV over 46 hours for the first 2 cycles, increased to 3000mg/m^2 thereafter if no significant side effects
Intervention MeSH terms: Leucovorin; Bevacizumab; Panitumumab; Fluorouracil; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 266.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: EGFR; FOLFIRI; 2nd Line Therapy; 2nd Line mCRC Therapy; mCRC; Irinotecan; panitumumab; bevacizumab

Summary:

      This is a multi-center, open-label, randomized, phase 2, two-arm clinical trial to be
      conducted in the United States. Approximately 210 eligible KRAS wild-type expressing
      metastatic colorectal cancer subjects who have failed first-line oxaliplatin-based
      chemotherapy (with at least 4 doses of oxaliplatin-based chemotherapy) with at least 4 doses
      of bevacizumab (failure is defined as toxicity due to oxaliplatin-based chemotherapy or
      progression of disease on first-line treatment) will be randomized in a 1:1 ratio to receive
      either a once-every-two-weeks (Q2W) FOLFIRI regimen plus panitumumab 6 mg/kg or a Q2W FOLFIRI
      regimen plus bevacizumab (either 5 mg/kg or 10 mg/kg, depending on physician choice and
      institutional standard of care).
    

Eligibility criteria:

        Inclusion Criteria

          -  Diagnosis of metastatic adenocarcinoma of the colon or rectum that cannot, in the
             opinion of the investigator, be cured by surgical resection at the time of
             randomization

          -  Wild-type KRAS expressing mCRC from the primary tumor or metastasis.

          -  Failure of prior first-line oxaliplatin-based chemotherapy with bevacizumab (at least
             four therapeutic doses of oxaliplatin-based chemotherapy and bevacizumab) for mCRC.

          -  At least one uni-dimensionally measurable lesion per modified RECIST criteria.

          -  Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Man or woman 18 years of age or older

          -  Hematology, chemistry, coagution, metabolic functions within normal or
             protocol-defined limits

        Exclusion Criteria

          -  Previous irinotecan, anti-EGFr therapy (eg, cetuximab, panitumumab, erlotinib,
             gefitinib, lapatinib) or vaccine for the treatment of mCRC

          -  Radiotherapy ≤ 14 days before randomization

          -  Evidence of central nervous system (CNS) metastases

          -  Unresolved toxicities from prior anti-cancer therapy that, in the opinion of the
             investigator, precludes subject from participation

          -  History of other invasive primary cancer, except:

          -  Curatively resected or treated non-melanomatous skin cancer

          -  Curatively treated cervical carcinoma in situ

          -  Other primary solid tumor treated curatively and no treatment administered ≤ 2 years
             before randomization and, in the investigator's opinion, it is unlikely that there
             will be a recurrence ≤ 2 years post randomization

        Medications

          -  C hronic daily treatment (as determined by the investigator) with aspirin (> 325
             mg/day) or non steroidal anti inflammatory agents known to inhibit platelet function

          -  Infection requiring a course of systemic anti-infectives that was completed ≤ 14 days
             before randomization (exception can be made at the judgment of the investigator for
             oral treatment of an uncomplicated urinary tract infection [UTI])

          -  Subjects concurrently receiving any investigational agent or therapy ≤ 30 days before
             randomization

        General:

          -  Significant cardiovascular risk as defined by the protocol

          -  History of peripheral arterial ischemia ≤ 24 weeks before randomization (subjects with
             brief, reversible, exercise-induced claudication are eligible)

          -  History of visceral arterial ischemia ≤ 24 weeks before randomization

          -  Significant bleeding risk:

          -  Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days
             before randomization

          -  Anticipation of need for major surgical procedures during the course of the study

          -  C ore biopsy or other minor procedure, excluding placement of a vascular access device
             ≤ 7 days before randomization

          -  A ny significant bleeding that is not related to the primary colon tumor ≤ 24 weeks
             before randomization

          -  P re-existing bleeding diathesis or coagulopathy with the exception of well-controlled
             chronic anticoagulation therapy

          -  Serious or non-healing wounds, skin ulcers, or unhealed bone fractures

          -  Gastroduodenal ulcer(s) determined by endoscopy to be active or uncontrolled
             gastrointestinal ulcer ≤ 28 days before randomization

          -  History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or
             evidence of interstitial lung disease on baseline chest x-ray (CXR) or computed
             tomography (CT) scan

          -  Clinically significant ascites

          -  Subjects known to be human immunodeficiency virus (HIV) positive or known to have
             chronic or active hepatitis B or C infection

          -  Men and women of childbearing potential (women who are post-menopausal < 52 weeks, not
             surgically sterilized, or not abstinent) who do not consent to use adequate
             contraception (according to institutional standard of care) during the course of the
             study and after the last date of receiving second-line treatment (24 weeks for women,
             4 weeks for men)

          -  Women who test positive for serum or urine pregnancy test ≤ 72 hours before
             randomization or are breast-feeding

          -  Subjects allergic to any component that is part of the treatment regimen