Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumor Malignancies

Conditions
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Advanced Solid Tumor Malignancy

Intervention / Treatment
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* Drug: CRLX301


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase 1 dose escalation study followed by phase 2a expansion cohort
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Schedule 1 Cohort 1<br>CRLX301 7.5 mg/m2 IV given every 3 weeks | Drug: CRLX301<br> <br> |
| Experimental: Schedule 1 Cohort 2<br>CRLX301 15 mg/m2 IV given every 3 weeks | Drug: CRLX301<br> <br> |
| Experimental: Schedule 1 Cohort 3<br>CRLX301 30 mg/m2 IV given every 3 weeks | Drug: CRLX301<br> <br> |
| Experimental: Schedule 1 Cohort 4<br>CRLX301 60 mg/m2 IV given every 3 weeks | Drug: CRLX301<br> <br> |
| Experimental: Schedule 1 Cohort 5<br>CRLX301 75 mg/m2 IV given every 3 weeks | Drug: CRLX301<br> <br> |
| Experimental: Schedule 1 Cohort 6<br>CRLX301 90 mg/m2 IV given every 3 weeks | Drug: CRLX301<br> <br> |
| Experimental: Schedule 2 Cohort 1<br>CRLX301 25 mg/m2 IV given weekly | Drug: CRLX301<br> <br> |
| Experimental: Schedule 2 Cohort 2<br>CRLX301 35 mg/m2 IV given weekly | Drug: CRLX301<br> <br> |
| Experimental: Schedule 2 Cohort 3<br>CRLX301 45 mg/m2 IV given weekly | Drug: CRLX301<br> <br> |
| Experimental: Schedule 2 Cohort 4<br>CRLX301 54 mg/m2 IV given weekly | Drug: CRLX301<br> <br> |
| Experimental: Schedule 2 Cohort 5<br>CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off | Drug: CRLX301<br> <br> |
| Experimental: Phase 2a expansion cohort<br>CRLX301 75mg/m2 IV given every 3 weeks | Drug: CRLX301<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities | Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed. | 13 to 19 months | 
| Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability | Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Pharmacokinetic (PK) Profile of CRLX301 | 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. | 2.5 years | 
| Percentage of Participants Stratified by Best Overall Tumor Response | Best overall tumor response will be provided per dose cohort using RECIST 1.1 | 2.5 years |