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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumor Malignancy
• Intervention / Treatment: Drug: CRLX301

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Houston, Texas, United States
      • MD Anderson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

12

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: NewLink Genetics Corporation
• Investigators: Principal Investigator: Elizabeth Dees, MD, University of North Carolina

Publications and helpful links

General Publications

• Piha-Paul SA, Thein KZ, De Souza P, Kefford R, Gangadhar T, Smith C, Schuster S, Zamboni WC, Dees CE, Markman B. First-in-human, phase I/IIa study of CRLX301, a nanoparticle drug conjugate containing docetaxel, in patients with advanced or metastatic solid malignancies. Invest New Drugs. 2021 Aug;39(4):1047-1056. doi: 10.1007/s10637-021-01081-x. Epub 2021 Feb 16.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (ACTUAL): October 4, 2017
• Study Completion (ACTUAL): October 4, 2017

Study Registration Dates

• First Submitted: February 19, 2015
• First Submitted That Met QC Criteria: March 2, 2015
• First Posted (ESTIMATE): March 5, 2015

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2020
• Last Update Submitted That Met QC Criteria: May 26, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CRLX301-101