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

Advanced Solid Tumor Malignancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02380677
• Other study ID #: CRLX301-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 2015
• Est. completion date: October 4, 2017

Study information

• Verified date: May 2020
• Source: Lumos Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: October 4, 2017
• Est. primary completion date: October 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor Malignancy
• Neoplasms

Intervention

Drug:
• CRLX301

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	MD Anderson	Houston	Texas
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
NewLink Genetics Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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