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

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

Sponsors

Lead sponsor: NewLink Genetics Corporation

Source 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.

Overall Status Terminated
Start Date April 2015
Completion Date October 4, 2017
Primary Completion Date October 4, 2017
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of CRLX301 in Phase 1 13 to 19 months
Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of CRLX301 in Phase 1 13 to 19 months
Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of CRLX301 in Phase 1 13 to 19 months
Number of Participants with Adverse Events as a Measure of Safety and Tolerability 12 months
Number of Participants with Adverse Events as a Measure of Safety and Tolerability 12 months
Number of Participants with Adverse Events as a Measure of Safety and Tolerability 12 months
Secondary Outcome
Measure Time Frame
Evaluate the pharmacokinetic (PK) profile of CRLX301 in blood and/or urine specimens of patients receiving at least 1 dose 2.5 years
Explore preliminary signs of efficacy of CRLX301 2.5 years
Enrollment 42
Condition
Intervention

Intervention type: Drug

Intervention name: CRLX301

Eligibility

Criteria:

Inclusion Criteria:

1. Male or female ≥18 years of age

2. Diagnosis of histologically or cytologically confirmed, advanced solid tumor malignancy that is refractory to or not a candidate for standard therapy

3. ECOG 0 or 1

4. Life expectancy >12 weeks

5. Fertile males or females of childbearing potential agree to use adequate contraception prior to study entry

6. Negative urine pregnancy test

Exclusion Criteria:

1. Uncontrolled grade 2 or greater toxicity except alopecia

2. Prolongation of QT/QTc interval

3. Women who are pregnant or nursing

4. Any known HIV infection or AIDS or any concurrent infection requiring IV antibiotics

5. Any chronic or concurrent acute liver disease, including viral hepatitis

6. Primary brain malignant tumors

7. Known metastases to the brain

8. Uncontrolled hypertension

9. Concurrent participation in any other investigational study

10. Concurrent treatment with anticoagulation medication, unless approved by Sponsor

11. History of stroke, deep venous thrombosis (DVT), or transient ischemic attack (TIA)

12. 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

13. Uncontrolled concurrent disease or illness

14. History of severe hypersensitivity reaction to taxanes

15. Peripheral neuropathy exclusions

16. 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Elizabeth Dees, MD Principal Investigator University of North Carolina
Location
facility
University of North Carolina at Chapel Hill
University of Pennsylvania
MD Anderson
Location Countries

United States

Verification Date

October 2019

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 12
Arm Group

Arm group label: Schedule 1 Cohort 1

Arm group type: Experimental

Description: CRLX301 7.5 mg/m2 IV given every 3 weeks

Arm group label: Schedule 1 Cohort 2

Arm group type: Experimental

Description: CRLX301 15 mg/m2 IV given every 3 weeks

Arm group label: Schedule 1 Cohort 3

Arm group type: Experimental

Description: CRLX301 30 mg/m2 IV given every 3 weeks

Arm group label: Schedule 1 Cohort 4

Arm group type: Experimental

Description: CRLX301 60 mg/m2 IV given every 3 weeks

Arm group label: Schedule 1 Cohort 5

Arm group type: Experimental

Description: CRLX301 75 mg/m2 IV given every 3 weeks

Arm group label: Schedule 1 Cohort 6

Arm group type: Experimental

Description: CRLX301 90 mg/m2 IV given every 3 weeks

Arm group label: Schedule 2 Cohort 1

Arm group type: Experimental

Description: CRLX301 25 mg/m2 IV given weekly

Arm group label: Schedule 2 Cohort 2

Arm group type: Experimental

Description: CRLX301 35 mg/m2 IV given weekly

Arm group label: Schedule 2 Cohort 3

Arm group type: Experimental

Description: CRLX301 45 mg/m2 IV given weekly

Arm group label: Schedule 2 Cohort 4

Arm group type: Experimental

Description: CRLX301 54 mg/m2 IV given weekly

Arm group label: Schedule 2 Cohort 5

Arm group type: Experimental

Description: CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off

Arm group label: Phase 2a expansion cohort

Arm group type: Experimental

Description: CRLX301 75mg/m2 IV given every 3 weeks

Study Design Info

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Intervention model description: Phase 1 dose escalation study followed by phase 2a expansion cohort

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov