LCCC 1315 CRLX 101 and Capecitabine

This trial will enroll patients with locally advanced rectal cancer (resectable and non-resectable).The phase Ib dose escalation portion of trial is designed to determine the maximum tolerated dose (MTD) of CRLX101 when combined with standard neoadjuvant therapies capecitabine (Cape) and radiation therapy (XRT). CRLX101 is a nanopharmaceutical (NP) formulation of camptothecin. These results will determine the recommended phase II dose (RP2D) for CRLX101 in this setting. The phase II portion of the trial is designed to evaluate the efficacy and safety of CRLX101 at the RP2D, when combined with capecitabine and radiation therapy prior to surgery.
Cancer (Oncology) - Rectal, Cancer (Oncology)
Somasundaram Subramaniam, MD
Swedish Cancer Institute
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. ECOG performance score ≤ 2
  2. Phase Ib and II: surgical candidates, with moderate to high-risk pathologically-confirmed rectal cancer (stage cT3-4N0 or cT1-4N+); clinical staging by endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI) is permitted.

    Phase Ib only:

    • Patients with metastatic rectal cancer are allowed if their primary site meets other eligibility criteria and chemoradiotherapy is recommended as initial therapy for symptom palliation by the multidisciplinary treating team
    • Patients with locally advanced unresectable rectal cancer are allow provided:

      • There is no evidence of recto-vaginal, recto-vesicular, recto-intestinal fistulization
      • Standard dose and schedule chemoradiotherapy is recommended as initial therapy by the multidisciplinary treating team
  3. Age ≥18 years old
  4. Women of childbearing potential (WOCBP) must have negative pregnancy test within 7 days prior to D1 of treatment
  5. Recommendation to undergo concurrent chemoradiation, as determined by the treating physician
  6. Ability to swallow oral medications
  7. As determined by the enrolling physician or protocol designee, ability of the patient to understand and comply with study procedures for the entire length of the study
  8. Informed consent reviewed and signed

Exclusion Criteria:

Patients meeting any of the following exclusion criteria will not be able to participate in this study:

  1. Grade 2 or higher diarrhea at baseline unless deemed by the investigator to be caused by laxatives prescribed for symptomatic partial obstruction (e.g. MiraLAX®)
  2. Not deemed a candidate for concurrent chemoradiation for medical reasons, such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient.
  3. Specific laboratory exclusion values, including:

    • Hemoglobin < 10.0 g/dL for males and ≤ 9.0 g/dL for females (transfusion allowed to achieve or maintain levels)
    • ANC < 1,500/mm3
    • Platelet count < 100,000/mm3
    • ALT and AST > 2.5 times upper level of normal (ULN)
    • Alkaline phosphatase > 2.5 times ULN
    • Total bilirubin > 1.5 times ULN
    • Creatinine clearance < 50 mL/min
    • INR >2
  4. Known dihydropyrimidine dehydrogenase (DPD) deficiency
  5. History of Gilbert's syndrome
  6. Those who require therapeutic anticoagulation with coumarin-derivative anticoagulants
  7. Unable to provide informed consent
  8. Receiving any other concurrent cytotoxic, biologic agent(s) or investigational agent
  9. Patients with a "currently active" second malignancy other than non-melanoma skin cancers, non-invasive bladder cancer, "low risk" adenocarcinoma of the prostate and carcinoma in situ of the cervix. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 2 years.
  10. Previous pelvic radiation therapy
  11. Prior treatment with a topoisomerase I inhibitor (i.e. irinotecan, topotecan)
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