Colorectal Cancer, Colorectal Adenocarcinoma, Colo-rectal Cancer, Colorectal Cancer Metastatic
Conditions
Keywords
DKK1, colorectal cancer, DKN-01
Brief summary
This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) \[FOLFIRI/FOLFOX and bevacizumab\] as second-line treatment of advanced CRC patients.
Detailed description
This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) \[FOLFIRI/FOLFOX and bevacizumab\] as second-line treatment of advanced CRC patients. In Parts A and B, approximately 200 evaluable adult advanced CRC patients with measurable disease (RECIST v1.1) who have radiographically progressed during or following 1 line of systemic treatment will be enrolled in the study. The study consists of a Screening Period, a Treatment Period, a Safety Follow-up Period (SFUP) and a Long-Term Follow-up Period (LTFU). Patients will be followed in the SFUP for approximately 30 days (+7 days) after the last administration of study drug and then enter the LTFU period to be followed for survival and subsequent therapies. Additionally, patients that ended study treatment for a reason unrelated to progressive disease \[PD\] will also be followed for disease progression in the LTFU period.
Interventions
DRUGDKN-01
30 minute IV infusion (400mg) every two weeks with an additional loading dose in the first cycle of treatment
DRUGFOLFIRI
90-min IV infusion of irinotecan, leucovorin, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks
DRUGBevacizumab
90-min IV infusion (5mg)
DRUGFOLFOX
2 hour IV infusion of oxaliplatin, folinic acid, and fluorouracil followed by a continuous 46-hour infusion of fluorouracil every two weeks
Sponsors
Leap Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adult patients with advanced CRC with measurable disease (RECIST v1.1) who have radiographically progressed during or following one line of systemic treatment will be enrolled in the study. Inclusion Criteria: Patients meeting all of the following criteria will be considered eligible for study entry: 1. Disease progression following first-line systemic therapy with any fluoropyrimidine-based regimen for advanced disease (except FOLFOXIRI, see
Exclusion criteria
). • Patients may have received prior neoadjuvant or adjuvant therapy which could have included irinotecan or oxaliplatin. If progression has occurred within 12 months from last dose of neoadjuvant or adjuvant treatment, this regimen will be considered as the one line of systemic therapy for advanced disease. * If assigned to receive FOLFIRI, patient may have received no prior irinotecan as part of first-line systemic therapy. * If assigned to receive FOLFOX, patient may have received no prior oxaliplatin as part of first line systemic therapy. * Prior treatment with an anti-VEGF or anti-EGFR therapy is allowed as first-line and/or maintenance systemic therapy. 2. Able to provide written informed consent for any study specific procedures. 3. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1 4. Sufficient tumor tissue for mandatory pre-treatment evaluation (fresh biopsy \[preferred\], or archived tissue block specimen). 5. ECOG performance status ≤1 within 7 days of first dose of study drug. Acceptable liver, renal, hematologic, and coagulation function 6. Females of childbearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | approximately 6 months | PFS, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | approximately 6 months | ORR, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC |
| Duration of Response (DoR) | approximately 6 months | DoR, as determined by the Investigator per RECIST v1.1 of DKN-01 plus SOC versus SOC |
| Overall Survival (OS) | approximately 6 months | OS with DKN-01 plus SOC versus SOC |
| Incidence of ≥Grade 3 related treatment-related adverse events (TRAEs). | approximately 6 months | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Complete Response (DoCR) | approximately 6 months | DoCR using RECIST v1.1 |
| Exposure-response relationships for DKN-01 as data permit. | approximately 6 months | — |
| Duration of clinical benefit (DoCB) | approximately 6 months | DoCB as determined using RECIST v1.1, is defined as the time from the date of randomization (or date of registration for Part A patients) to the time of progressive disease or death due to any cause in patients who had a best overall response of complete response (CR), partial response (PR), or stable disease (SD) of ≥8 weeks |
| Durable clinical benefit (DCB) | approximately 6 months | DCB, defined as DoCB ≥180 days. Patients who have best overall response of PD or those having clinical benefit but DoCB lasting \<180 days will be considered as non-DCB. |
| Disease control rate (DCR) | approximately 6 months | DCR (i.e., CR+PR+SD at ≥8 weeks), as assessed by the Investigator using RECIST v1.1. |
| Time to response (TTR) | approximately 6 months | TTR, defined as the time from the date of randomization (or date of registration for Part A patients) to the assessment date of the first instance of an overall response of CR or PR. |
Countries
Germany, South Korea, United States
Outcome results
None listed