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

NCT ID: NCT02380677

Last Updated: 2020-06-09

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-30

Study Completion Date

2017-10-04

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.

Conditions

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Advanced Solid Tumor Malignancy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Phase 1 dose escalation study followed by phase 2a expansion cohort
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Schedule 1 Cohort 1

CRLX301 7.5 mg/m2 IV given every 3 weeks

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 1 Cohort 2

CRLX301 15 mg/m2 IV given every 3 weeks

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 1 Cohort 3

CRLX301 30 mg/m2 IV given every 3 weeks

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 1 Cohort 4

CRLX301 60 mg/m2 IV given every 3 weeks

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 1 Cohort 5

CRLX301 75 mg/m2 IV given every 3 weeks

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 1 Cohort 6

CRLX301 90 mg/m2 IV given every 3 weeks

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 2 Cohort 1

CRLX301 25 mg/m2 IV given weekly

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 2 Cohort 2

CRLX301 35 mg/m2 IV given weekly

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 2 Cohort 3

CRLX301 45 mg/m2 IV given weekly

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 2 Cohort 4

CRLX301 54 mg/m2 IV given weekly

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Schedule 2 Cohort 5

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

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Phase 2a expansion cohort

CRLX301 75mg/m2 IV given every 3 weeks

Group Type EXPERIMENTAL

CRLX301

Intervention Type DRUG

Interventions

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CRLX301

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NewLink Genetics Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elizabeth Dees, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Locations

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University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

MD Anderson

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 33594602 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CRLX301-101

Identifier Type: -

Identifier Source: org_study_id

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