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

NCT02380677 | Terminated Phase 1 Results

• 1 other identifier: CRLX301-101
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumor Malignancy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Evaluate the Pharmacokinetic (PK) Profile of CRLX301

  2.5 years

• Percentage of Participants Stratified by Best Overall Tumor Response

  2.5 years

Study Arms (12)

Schedule 1 Cohort 1

EXPERIMENTAL

CRLX301 7.5 mg/m2 IV given every 3 weeks

Drug: CRLX301

Schedule 1 Cohort 2

EXPERIMENTAL

CRLX301 15 mg/m2 IV given every 3 weeks

Drug: CRLX301

Schedule 1 Cohort 3

EXPERIMENTAL

CRLX301 30 mg/m2 IV given every 3 weeks

Drug: CRLX301

Schedule 1 Cohort 4

EXPERIMENTAL

CRLX301 60 mg/m2 IV given every 3 weeks

Drug: CRLX301

Schedule 1 Cohort 5

EXPERIMENTAL

CRLX301 75 mg/m2 IV given every 3 weeks

Drug: CRLX301

Schedule 1 Cohort 6

EXPERIMENTAL

CRLX301 90 mg/m2 IV given every 3 weeks

Drug: CRLX301

Schedule 2 Cohort 1

EXPERIMENTAL

CRLX301 25 mg/m2 IV given weekly

Drug: CRLX301

Schedule 2 Cohort 2

EXPERIMENTAL

CRLX301 35 mg/m2 IV given weekly

Drug: CRLX301

Schedule 2 Cohort 3

EXPERIMENTAL

CRLX301 45 mg/m2 IV given weekly

Drug: CRLX301

Schedule 2 Cohort 4

EXPERIMENTAL

CRLX301 54 mg/m2 IV given weekly

Drug: CRLX301

Schedule 2 Cohort 5

EXPERIMENTAL

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

Drug: CRLX301

Phase 2a expansion cohort

EXPERIMENTAL

CRLX301 75mg/m2 IV given every 3 weeks

Drug: CRLX301

Interventions

CRLX301 DRUG

Phase 2a expansion cohort; Schedule 1 Cohort 1; Schedule 1 Cohort 2; Schedule 1 Cohort 3; Schedule 1 Cohort 4; Schedule 1 Cohort 5; Schedule 1 Cohort 6; Schedule 2 Cohort 1; Schedule 2 Cohort 2; Schedule 2 Cohort 3; Schedule 2 Cohort 4; Schedule 2 Cohort 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• NewLink Genetics Corporation: lead

Study Sites (3)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson

Houston, Texas, United States

Location

Related Publications (1)

• 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.

  PMID: 33594602 DERIVED

Results Point of Contact

• Title: Manager, Clinical Operations
• Organization: NewLink Genetics Corporation

csmith@linkp.com

515-598-5020

Study Officials

• Elizabeth Dees, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 dose escalation study followed by phase 2a expansion cohort

Study Record Dates

• First Submitted: February 19, 2015
• First Posted: March 5, 2015
• Study Start: April 1, 2015
• Primary Completion: October 4, 2017
• Study Completion: October 4, 2017
• Last Updated: June 9, 2020
• Results First Posted: June 9, 2020

Record last verified: 2020-05

Locations

US (3)