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8110 Gatehouse Road, Falls Church, VA 22042

A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second-Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (TROV-054)

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General Information

Age Group

Adults

Status

Recruiting

Protocol Number

NCT03829410

Background Information

This study is designed for participants with histologically confirmed (through microscopic examination of tissue) metastatic or unresectable Colorectal Cancer (mCRC) with a KRAS mutation. This research study is studying a drug called Onvansertib in combination with FOLFIRI (a chemotherapy regimen) and bevacizumab (a recombinant humanized monoclonal IgG1 antibody) for second- line treatment. FOLFIRI (5-FU (fluorouracil) and irinotecan) and bevacizumab (Avastin®) are approved treatments for mCRC. The study aims to assess the tolerated dose, safety, and preliminary efficacy of this combination in participants with mCRC with a KRAS mutation who have failed or are intolerant of treatment with FOLFOX (5-FU (fluorouracil) and oxaliplatin) in the first-line setting. The name of the study drug involved in this research study is: Onvansertib, an oral highly-selective polo-like kinase 1 (PLK1) inhibitor, which helps to stop cancer cells from dividing and multiplying.

Offered At

Inova Schar Cancer Institute
8081 Innovation Park Drive
Fairfax, VA 22031
A Department of Inova Fairfax Hospital

Eligibility Information

  • Histologically confirmed metastatic and unresectable CRC
  • KRAS mutation in exon 2, 3 or 4 in primary tumor or metastasis. Subjects with concomitant KRAS and BRAF-V600 mutations are excluded from this study. Subjects with Microsatellite Instability High/Deficient Mismatch Repair are also ineligible
  • Age ≥ 18 years
  • ECOG Performance Status of 0 or 1 (Appendix 16.2)
  • Has failed treatment or is intolerant of fluoropyrimidine and oxaliplatin with or without bevacizumab. Treatment failure is defined as radiologic progression during or < 6 months after the last dose of first-line therapy
  • All participants must have received a minimum of 6 weeks of the first-line regimen that included oxaliplatin and a fluoropyrimidine with or without bevacizumab in the same cycle
  • Patients who show tumor progression while on maintenance therapy with a fluoropyrimidine with or without bevacizumab after prior fluoropyrimidine-oxaliplatin with or without bevacizumab induction therapy are eligible. Rechallenge with oxaliplatin is permitted and will be considered part of the first-line regimen for metastatic disease, with both initial oxaliplatin treatment and subsequent rechallenge being considered as one regimen
  • Patients who received oxaliplatin/fluoropyrimidine-based neoadjuvant or adjuvant therapy and have disease recurrence or progression > 6 months from their last dose of neoadjuvant or adjuvant treatment (or > 6 months from surgery if no adjuvant therapy was administered) will be required to receive fluoropyrimidine/oxaliplatin-based therapy with or without bevacizumab for metastatic disease
  • For patients with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen
  • Patients who discontinued first-line therapy because of toxicity may be enrolled for as long as progression occurred < 6 months after the last dose of first-line therapy
  • Additional eligibility in protocol

Ineligibility Information

  • More than one prior chemotherapy regimen administered in the metastatic setting
  • Untreated brain metastasis
  • Women who are pregnant or breastfeeding
  • Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would significantly impede the absorption of an oral agent (e.g., intestinal occlusion, active Crohn’s disease, ulcerative colitis, extensive gastric and small intestine resection)
  • Known active infection with Human Immunodeficiency Virus (HIV), with measurable viral titer, and/or active infection with hepatitis B or C (patients who have had a hepatitis B virus (HBV) immunization are eligible)
  • Known hypersensitivity to 5-fluorouracil/leucovorin
  • Known hypersensitivity to irinotecan
  • Abnormal glucuronidation of bilirubin, known Gilbert’s syndrome
  • Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 2 years
  • History of abdominal fistula, GI perforation, peptic ulcer, or intra-abdominal abscess within 6 months
  • Additional ineligibility in protocol

For additional information, please see: https://www.clinicaltrials.gov/ct2/show/NCT03829410