Trial Outcomes & Findings for Combining CRLX101, a Nanoparticle Camptothecin, With Enzalutamide in People With Progressive Metastatic Castration Resistant Prostate Cancer Following Prior Enzalutamide Treatment (NCT NCT03531827)

Last Updated: 2022-07-12

Results Overview

Anti-tumor activity is \>=50% prostate-specific antigen (PSA) decline or stable disease on imaging following 5 months of treatment in participants with progressive metastatic castration resistant prostate cancer (mCRPC) following enzalutamide treatment. Stable disease (SD) is neither sufficient shrinkage to qualify for partial response (at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

5 months

Results posted on

2022-07-12

Participant Flow

Participant milestones

Participant milestones
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+	2/Efficacy: CRLX101 With Enzalutamide Tolerable dose of CRLX101 (formerly IT-101) in combination with enzalutamide (8 participants, expandable to 21 total participants) enzalutamide: enzalutamide is an androgen receptor (AR) antagonist that is standard care therapy for metastatic prostate cancer CRLX101: CRLX101 is a nanoparticle-drug conjugate (NDC) comprised of a linear cyclodextrin-polyethylene glycol-base polymer conjugated to multiple 2 (S)-camptothecin (CPT) molecules (Poly-CD-PEG-Camptothecin)
Overall Study STARTED	4	0
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+	2/Efficacy: CRLX101 With Enzalutamide Tolerable dose of CRLX101 (formerly IT-101) in combination with enzalutamide (8 participants, expandable to 21 total participants) enzalutamide: enzalutamide is an androgen receptor (AR) antagonist that is standard care therapy for metastatic prostate cancer CRLX101: CRLX101 is a nanoparticle-drug conjugate (NDC) comprised of a linear cyclodextrin-polyethylene glycol-base polymer conjugated to multiple 2 (S)-camptothecin (CPT) molecules (Poly-CD-PEG-Camptothecin)
Overall Study Adverse Event	2	0
Overall Study Progressive disease	1	0

Baseline Characteristics

Combining CRLX101, a Nanoparticle Camptothecin, With Enzalutamide in People With Progressive Metastatic Castration Resistant Prostate Cancer Following Prior Enzalutamide Treatment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 Participants Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Age, Continuous	72.65 years STANDARD_DEVIATION 3.37 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants
Median Prostate-Specific Antigen (PSA)	93.7 ng/ml n=5 Participants
Median Prior Lines of Therapy	4.5 Lines of therapy n=5 Participants

PRIMARY outcome

Timeframe: 5 months

Outcome measures

Outcome measures
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 Participants Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Percentage of Participants With Anti-tumor Activity >=50% prostate-specific antigen (PSA) decline	25 percentage of participants
Percentage of Participants With Anti-tumor Activity Stable Disease	0 percentage of participants

SECONDARY outcome

Timeframe: time of sustained >30% decline in prostate-specific antigen (PSA) from baseline, approximately >1 month

Proportion of participants with a sustained \>30% decline in prostate-specific antigen (PSA) from baseline based on all evaluable participants.

Outcome measures

Outcome measures
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 Participants Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Proportion of Participants With a Sustained >30% Decline in Prostate-specific Antigen (PSA)	0 proportion of participants

SECONDARY outcome

Timeframe: time from the start of treatment to the time of death, up to 17.5 months

Population: 3/4 participants were analyzed because one participant was lost to follow-up.

OS is defined as the duration of time from the start of treatment to the time of death estimated based on all evaluable participants.

Outcome measures

Outcome measures
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=3 Participants Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Overall Survival (OS)	3.9 Months Interval 3.8 to 17.9

SECONDARY outcome

Timeframe: Within 6 months

Number of participants with a change in measurable disease as determined by RECIST. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

Outcome measures

Outcome measures
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 Participants Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Number of Participants With a Change in Measurable Disease From Baseline as Determined by Response Evaluation Criteria in Solid Tumors (RECIST)	0 Participants

SECONDARY outcome

Timeframe: Study end, approximately 6 months

Number of participants with a change in measurable disease as determined by the Prostate Cancer Working Group 3 (PCWG3). PSA values will be captured at each visit and PSA declines and progression (by radiographic evidence or clinical symptoms) will be followed. Radiographic disease progression is considered if a minimum of two new lesions is observed on bone scan. Clinical disease progression is the need for chemotherapy or other change in therapy based on increased cancer related symptoms.

Outcome measures

Outcome measures
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 Participants Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Number of Participants With a Change in Measurable Disease as Determined by the Prostate Cancer Working Group 3 (PCWG3)	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 26 months and 6 days.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 Participants Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	4 Participants

Adverse Events

1/Lead-In Safety: CRLX101 With Enzalutamide

Serious events: 3 serious events

Other events: 4 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 participants at risk Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Renal and urinary disorders Cystitis noninfective	50.0% 2/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
General disorders Death NOS	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Gastrointestinal disorders Gastroesophageal reflux disease	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Nervous system disorders Syncope	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.

Other adverse events

Other adverse events
Measure	1/Lead-In Safety: CRLX101 With Enzalutamide n=4 participants at risk Lead-in Dosing: CRLX101 (formerly IT-101) 12mg/m\^2 every (q) 2 weeks x 2 cycles; CRLX101 15mg/m\^2 (q) 2 weeks cycle 3+; enzalutamide 160 mg every day (QD) cycle 1 day 2+
Gastrointestinal disorders Abdominal pain	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Blood and lymphatic system disorders Anemia	75.0% 3/4 • Number of events 10 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Musculoskeletal and connective tissue disorders Back pain	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Investigations Creatinine increased	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Nervous system disorders Dizziness	25.0% 1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Nervous system disorders Dysarthria	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
General disorders Edema limbs	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Eye disorders Eye disorders - Other, subconjunctival hemorrhage, left eye	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Injury, poisoning and procedural complications Fall	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
General disorders Fatigue	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Renal and urinary disorders Hematuria	50.0% 2/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Metabolism and nutrition disorders Hyponatremia	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Metabolism and nutrition disorders Hypophosphatemia	25.0% 1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Vascular disorders Hypotension	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Investigations Lymphocyte count decreased	50.0% 2/4 • Number of events 6 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Gastrointestinal disorders Nausea	75.0% 3/4 • Number of events 3 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Investigations Neutrophil count decreased	25.0% 1/4 • Number of events 5 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
General disorders Pain	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Nervous system disorders Peripheral sensory neuropathy	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Investigations Platelet count decreased	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, Dx cough/URI	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Infections and infestations Skin infection	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Gastrointestinal disorders Toothache	25.0% 1/4 • Number of events 1 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Investigations Weight loss	25.0% 1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 26 months and 6 days.
Investigations White blood cell decreased	25.0% 1/4 • Number of events 2 • Date treatment consent signed to date off study, approximately 26 months and 6 days.

Additional Information

Dr. Ravi Madan

National Cancer Institute

Phone: 301.480-7168

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place