Patient case: 35-year-old female with Colorectal cancer. Genetic variant: FGFR1 Amplification. Other conditions: None.

Clinical trial: Ph 1 Study ADI-PEG 20 Plus FOLFOX in Subjects With Advanced Gastrointestinal Malignancies

Summary: Assessment of safety and tolerability of ADI-PEG 20 in combination with folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX) in advanced GI malignancies.


Eligibility: Inclusion Criteria:
  For Advanced GI Malignancies (Dose Escalation and MTD Cohorts):
  1. Advanced histologically proven GI cancer.
  2. First line or progressive disease if already treated with any form of therapy, including but not limited to chemotherapy, radiotherapy, local therapy, surgery or immuno-therapy. Patients with HCC who failed sorafenib, with documented PD or AEs that resulted in discontinuance of that agent. Patients with pancreatic cancer (dose escalation only) who have progressed following a gemcitabine based regimen. Subjects failing prior platinum containing regimens are eligible. Gastric cancer subjects that express tumor HER-2 amplification must be treated with trastuzumab prior to enrollment, unless trastuzumab is not available for those indications in a particular country.
  3. Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapy such as (but not limited to) chemoembolization, embolization, cryoablation, hepatic artery therapy, percutaneous ethanol injection, radiation therapy, radiofrequency ablation or surgery are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan.
  4. ECOG performance status of 0 - 1.
  5. Expected survival of at least 3 months.
  For HCC (Dose Escalation and MTD Expansion):
  19. Prior treatment with sorafenib, with documented PD or AEs that resulted in discontinuance of that agent. Patient may have been treated with other lines off therapy as well excluding ADI-PEG 20.
  20. Cirrhotic status of Child-Pugh grade A. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C). Subjects on Coumadin anti-coagulants are to receive only 1 point for their INR status.
  21. Serum albumin level ≥ 2.8 g/dl. 22. Prothrombin time (PT)-international normalized ratio (INR): PT <6 seconds above control or INR <1.7. Subjects on Coumadin anti-coagulants are to receive only 1 point for their INR status.
  23. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.
  Exclusion Criteria:
  1. Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
  2. Pregnancy or lactation.
  3. Expected non-compliance.
  4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
  5. Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline (except alopecia) or ≤ Grade 1 AEs, or deemed irreversible from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a safety risk by the Sponsor and investigator may be allowed upon agreement with both.

Relevance to patient case: not relevant