Advanced Solid Tumor MalignancyPhase 1/2NCT02380677

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

A Phase 1/2 study testing CRLX301 in people with Advanced Solid Tumor Malignancy, run by NewLink Genetics Corporation at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Solid Tumor Malignancy
What is being tested?: CRLX301
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 42 participants
Where: 3 sitesUnited States
Study dates: Apr 2015to 4 Oct 2017
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 16Show fewer

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
Peripheral neuropathy exclusions
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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

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

Other trials in United States

About this study

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

Read the 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.

Conditions: Advanced Solid Tumor Malignancy
Being tested: CRLX301

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CRLX301Drug

Study groups in NCT02380677
Study group	Role	What they receive
Schedule 1 Cohort 1	Experimental	CRLX301 7.5 mg/m2 IV given every 3 weeks Receives: Drug: CRLX301
Schedule 1 Cohort 2	Experimental	CRLX301 15 mg/m2 IV given every 3 weeks Receives: Drug: CRLX301
Schedule 1 Cohort 3	Experimental	CRLX301 30 mg/m2 IV given every 3 weeks Receives: Drug: CRLX301
Schedule 1 Cohort 4	Experimental	CRLX301 60 mg/m2 IV given every 3 weeks Receives: Drug: CRLX301
Schedule 1 Cohort 5	Experimental	CRLX301 75 mg/m2 IV given every 3 weeks Receives: Drug: CRLX301
Schedule 1 Cohort 6	Experimental	CRLX301 90 mg/m2 IV given every 3 weeks Receives: Drug: CRLX301
Schedule 2 Cohort 1	Experimental	CRLX301 25 mg/m2 IV given weekly Receives: Drug: CRLX301
Schedule 2 Cohort 2	Experimental	CRLX301 35 mg/m2 IV given weekly Receives: Drug: CRLX301
Schedule 2 Cohort 3	Experimental	CRLX301 45 mg/m2 IV given weekly Receives: Drug: CRLX301
Schedule 2 Cohort 4	Experimental	CRLX301 54 mg/m2 IV given weekly Receives: Drug: CRLX301
Schedule 2 Cohort 5	Experimental	CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off Receives: Drug: CRLX301
Phase 2a expansion cohort	Experimental	CRLX301 75mg/m2 IV given every 3 weeks Receives: Drug: CRLX301

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 12 months

Secondary outcomes (2)

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.
Measured: 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
Measured: 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 20154 Oct 2017

First posted5 Mar 2015 (estimated)
Study startApr 2015
Primary completion4 Oct 2017
Study completion4 Oct 2017

Why it stopped: Company decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Advanced Solid Tumor MalignancyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Phase 1 dose escalation study followed by phase 2a expansion cohort
Masking: None (open label)
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02380677
Sponsor's protocol ID: CRLX301-101
Status last verified: May 2020
First submitted: 19 Feb 2015
Last updated: 9 Jun 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 33594602

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

All Advanced Solid Tumor Malignancy trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumor Malignancies
ClinicalTrials.gov ID: NCT02380677
Acronym / sponsor ID: CRLX301-101
Conditions: Advanced Solid Tumor Malignancy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Company decision
Enrolment: 42 participants (actual)
Lead sponsor: NewLink Genetics CorporationIndustry (pharma, biotech, devices)
Study start: Apr 2015
Primary completion: 4 Oct 2017 (actual)
Study completion: 4 Oct 2017 (actual)
First posted: 5 Mar 2015 (estimated)
Results: Posted 9 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 12
Model description: Phase 1 dose escalation study followed by phase 2a expansion cohort

Arm	Type	Receives
Schedule 1 Cohort 1	Experimental	Drug: CRLX301CRLX301 7.5 mg/m2 IV given every 3 weeks
Schedule 1 Cohort 2	Experimental	Drug: CRLX301CRLX301 15 mg/m2 IV given every 3 weeks
Schedule 1 Cohort 3	Experimental	Drug: CRLX301CRLX301 30 mg/m2 IV given every 3 weeks
Schedule 1 Cohort 4	Experimental	Drug: CRLX301CRLX301 60 mg/m2 IV given every 3 weeks
Schedule 1 Cohort 5	Experimental	Drug: CRLX301CRLX301 75 mg/m2 IV given every 3 weeks
Schedule 1 Cohort 6	Experimental	Drug: CRLX301CRLX301 90 mg/m2 IV given every 3 weeks
Schedule 2 Cohort 1	Experimental	Drug: CRLX301CRLX301 25 mg/m2 IV given weekly
Schedule 2 Cohort 2	Experimental	Drug: CRLX301CRLX301 35 mg/m2 IV given weekly
Schedule 2 Cohort 3	Experimental	Drug: CRLX301CRLX301 45 mg/m2 IV given weekly
Schedule 2 Cohort 4	Experimental	Drug: CRLX301CRLX301 54 mg/m2 IV given weekly
Schedule 2 Cohort 5	Experimental	Drug: CRLX301CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off
Phase 2a expansion cohort	Experimental	Drug: CRLX301CRLX301 75mg/m2 IV given every 3 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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

Key exclusion criteria (16 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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

Primary outcome

Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities
Time frame: 13 to 19 months
Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed.
Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 12 months
Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects.

2 secondary outcomes

Evaluate the Pharmacokinetic (PK) Profile of CRLX301
Time frame: 2.5 years
Percentage of Participants Stratified by Best Overall Tumor Response
Time frame: 2.5 years

Results and safety

Results posted to the registry on 9 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Schedule 1 Cohort 1	1	0
Schedule 1 Cohort 2	1	0
Schedule 1 Cohort 3	3	0
Schedule 1 Cohort 5	3	0
Schedule 1 Cohort 6	6	0
Schedule 1 Cohort 7	6	0
Schedule 2 Cohort 1	3	0
Schedule 2 Cohort 2	4	0
Schedule 2 Cohort 3	4	0
Schedule 2 Cohort 4	2	0
Schedule 2 Cohort 5	4	0
Phase 2a Expansion Cohort	5	0

Primary outcome: Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities

Time frame: 13 to 19 months. Number. Unit: Patients with event

Measure	Schedule 1 Cohort 1 n = 1	Schedule 1 Cohort 2 n = 1	Schedule 1 Cohort 3 n = 3	Schedule 1 Cohort 5 n = 3	Schedule 1 Cohort 6 n = 6	Schedule 1 Cohort 7 n = 6	Schedule 2 Cohort 1 n = 3	Schedule 2 Cohort 2 n = 4	Schedule 2 Cohort 3 n = 4	Schedule 2 Cohort 4 n = 2	Schedule 2 Cohort 5 n = 4
At least one TEAE	1	1	3	3	6	6	3	4	4	2	4
At least one Serious TEAE	0	1	3	3	1	3	1	2	1	1	0
At least one DLT	0	0	0	0	0	2	0	0	0	0	0
At least one severe TEAE	0	1	3	3	4	6	0	2	2	2	4
At least one related TEAE	1	1	2	3	6	6	3	3	4	2	4
At least one TEAE leading to discontinuation	0	0	0	2	1	4	2	1	2	1	0

Population analysed: The phase 1 safety population were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study.

Primary outcome: Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability

Time frame: 12 months. Number. Unit: Patients with event

Measure	Phase 2a Expansion Cohort n = 5
At least one TEAE	5
At least one Serious TEAE	2
At least one severe TEAE	5
At least one related TEAE	5
At least one TEAE leading to discontinuation	2

Population analysed: The safety population (all patients) were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: All AEs were collected occurring during the study period from the time of the first dose to the last day of the 30-day post-treatment follow-up period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Schedule 1 Cohort 1	0 of 1 (0%)	1 of 1 (100%)	0 of 1
Schedule 1 Cohort 2	1 of 1 (100%)	1 of 1 (100%)	1 of 1
Schedule 1 Cohort 3	3 of 3 (100%)	3 of 3 (100%)	1 of 3
Schedule 1 Cohort 5	3 of 3 (100%)	3 of 3 (100%)	1 of 3
Schedule 1 Cohort 6	1 of 6 (16.7%)	6 of 6 (100%)	0 of 6
Schedule 1 Cohort 7	3 of 6 (50%)	6 of 6 (100%)	0 of 6
Schedule 2 Cohort 1	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Schedule 2 Cohort 2	2 of 4 (50%)	4 of 4 (100%)	2 of 4
Schedule 2 Cohort 3	1 of 4 (25%)	4 of 4 (100%)	0 of 4
Schedule 2 Cohort 4	1 of 2 (50%)	2 of 2 (100%)	0 of 2
Schedule 2 Cohort 5	0 of 4 (0%)	4 of 4 (100%)	0 of 4
Phase 2a Expansion Cohort	2 of 5 (40%)	5 of 5 (100%)	1 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33594602Piha-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.

Related trials for Advanced Solid Tumor Malignancy

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Elizabeth Dees, MD principal investigator

University of North Carolina

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CRLX301 in people with Advanced Solid Tumor Malignancy, run by NewLink Genetics Corporation at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities (time frame: 13 to 19 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02380677, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.