Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumors
- Registration Number
- NCT02380677
- Lead Sponsor
- NewLink Genetics Corporation
- Brief Summary
A Phase 1/2a, open-label, dose-escalation study with enrollment in Phase 1 to continue until determination of the Maximum Tolerated Dose (MTD) /Recommended Phase 2a Dose (RP2D), and then enrollment into Phase 2a expansion cohorts will be initiated.
- Detailed Description
Phase 1 is an open-label, dose-escalation protocol. It is anticipated that up to 36 patients will be enrolled in Phase 1. All patients will be assigned to treatment with CRLX301 as the single agent.
For the first 2 cohorts a 1+5 study design will be utilized. A single patient will be enrolled sequentially into cohort 1 and cohort 2. If either patient in cohort 1 or 2 experiences a dose limiting toxicity (DLT) during Cycle 1, then the cohort will be expanded to enroll additional patients up to a total of 6.
As of cohort 3 and for all subsequent cohorts, a 3+3 dose escalation schema will be utilized.
MTD/RP2D will be determined at the dose level when \<2 of 6 patients experience a DLT in a cohort.
The Phase 2a part of the study will be an open-label expansion cohort study. An additional 24 patients with advanced, histologically confirmed solid tumor malignancies will be enrolled. All patients will be assigned to treatment at the MTD/RP2D with CRLX301 as the single agent.
All patients will be followed for safety, tumor response, and progression free survival (PFS) all per RECIST version 1.1 guidelines. Patients will remain on study treatment until they experience progression of disease, unacceptable toxicity, or other specified reason for discontinuation.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 42
- Male or female ≥18 years of age
- Diagnosis of histologically or cytologically confirmed, advanced solid tumor malignancy that is refractory to or not a candidate for standard therapy
- ECOG 0 or 1
- Life expectancy >12 weeks
- Fertile males or females of childbearing potential agree to use adequate contraception prior to study entry
- Negative urine pregnancy test
- Uncontrolled grade 2 or greater toxicity except alopecia
- Prolongation of QT/QTc interval
- Women who are pregnant or nursing
- Any known HIV infection or AIDS or any concurrent infection requiring IV antibiotics
- Any chronic or concurrent acute liver disease, including viral hepatitis
- Primary brain malignant tumors
- Known metastases to the brain
- Uncontrolled hypertension
- Concurrent participation in any other investigational study
- Concurrent treatment with anticoagulation medication, unless approved by Sponsor
- History of stroke, deep venous thrombosis (DVT), or transient ischemic attack (TIA)
- History of other cancer type, except for cutaneous basal cell or squamous cell carcinoma, or cervical or prostate cancer in situ, within the last 2 years prior to C1D1
- Uncontrolled concurrent disease or illness
- History of severe hypersensitivity reaction to taxanes
- Peripheral neuropathy exclusions
- Other condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Schedule 2 Cohort 3 CRLX301 CRLX301 45 mg/m2 IV given weekly Schedule 1 Cohort 1 CRLX301 CRLX301 7.5 mg/m2 IV given every 3 weeks Schedule 2 Cohort 4 CRLX301 CRLX301 54 mg/m2 IV given weekly Schedule 1 Cohort 2 CRLX301 CRLX301 15 mg/m2 IV given every 3 weeks Schedule 1 Cohort 3 CRLX301 CRLX301 30 mg/m2 IV given every 3 weeks Schedule 1 Cohort 6 CRLX301 CRLX301 90 mg/m2 IV given every 3 weeks Schedule 2 Cohort 2 CRLX301 CRLX301 35 mg/m2 IV given weekly Phase 2a expansion cohort CRLX301 CRLX301 75mg/m2 IV given every 3 weeks Schedule 1 Cohort 5 CRLX301 CRLX301 75 mg/m2 IV given every 3 weeks Schedule 2 Cohort 1 CRLX301 CRLX301 25 mg/m2 IV given weekly Schedule 2 Cohort 5 CRLX301 CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off Schedule 1 Cohort 4 CRLX301 CRLX301 60 mg/m2 IV given every 3 weeks
- Primary Outcome Measures
Name Time Method Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability 12 months Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects.
Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities 13 to 19 months Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed.
- Secondary Outcome Measures
Name Time Method Evaluate the Pharmacokinetic (PK) Profile of CRLX301 2.5 years Area under the concentration vs time curve of released docetaxel in blood and/or urine specimens of patients receiving at least 1 dose of CRLX301.
Percentage of Participants Stratified by Best Overall Tumor Response 2.5 years Best overall tumor response will be provided per dose cohort using RECIST 1.1
Related Research Topics
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Trial Locations
- Locations (3)
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
MD Anderson
🇺🇸Houston, Texas, United States