SHS_492292 SUBS CUNC 15085

Phase Ib/II Study of Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Locally Advanced Rectal Cancer

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.

Inclusion Criteria:
ECOG performance score ? 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. Age ?18 years old. Ability to swallow oral medications.

Exclusion Criteria:
Grade 2 or higher diarrhea at baseline unless deemed by the investigator to be caused by laxatives prescribed for symptomatic partial obstruction. Not deemed a candidate for concurrent chemoradiation for medical reasons. Specific laboratory exclusion values (see protocol). Known dihydropyrimidine dehydrogenase (DPD) deficiency. History of Gilbert's syndrome. Those who require therapeutic anticoagulation with coumarin-derivative anticoagulants. Receiving any other concurrent cytotoxic, biologic agent(s) or investigational agent. 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. Previous pelvic radiation therapy. Prior treatment with a topoisomerase I inhibitor.
Phase I/II
Somasundaram Subramaniam, M.D.
Erik Bailey
  • Swedish Medical Center