Dose finding study for CRLX301 in solid tumors

Phase 1

• Conditions: Solid Tumours; Taxane-naive castration resistant prostate cancer (CRPC); Cancer - Other cancer types; Cancer - Prostate

• Registration Number: ACTRN12614001292662
• Lead Sponsor: BlueLink Pharmaceuticals a subsidiary of NewLink Genetics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-12-11
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 118

Inclusion Criteria

1. Male or female adult patients older than or equal to 18 years of age
2. Diagnosis of histologically or cytologically confirmed, advanced solid tumour malignancy:
a) For Phase 1: that is refractory to standard therapy and/or for whom no further standard therapy is available, especially for those for whom taxane chemotherapy may be a reasonable therapeutic choice, in the opinion of the Investigator.
b) For Phase 2a: advanced/metastatic tumours considered responsive to taxanes
c) For prostate cancer patients in Phase 2a: that is castration resistant prostate cancer (CRPC*) and has not been previously treated with taxanes but has been treated with abiraterone and/or enzalutamide.
3. For patients enrolled in Phase 2a only: at least one measurable target lesion as defined by RECIST 1.1 criteria for solid tumours, except for patients with advanced prostate cancer (in which case as per the PCWG2 criteria). Tumours within a previously irradiated field should be designated as non-target” unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
4. If Patient has received:
a) approved chemotherapy or small molecule targeted therapy; it has been at least 2 weeks since last dose before CRLX301 first dose.
b) investigational therapy; it has been more than 30 days before first dose
c) local palliative radiation; it has been more than 14 days prior to first dose
d) radiation or invasive surgery requiring general anesthesia; it has been more than 30 days prior to first dose
e) chemotherapy with nitrosoureas or mitomycin C; it has been more than 45 days before first dose
5. ECOG Performance Status of 0 or 1
6. Life expectancy in opinion of Investigator of more than 12 weeks
7. Patients with acceptable pre-study hematology and biochemistry labs less than 72 hours prior to first dose
8. Fertile males or females of childbearing potential agree to use adequate contraception prior to study entry and for 30 days following last dose of study drug
9. Negative urine pregnancy test less than 72 hours prior to first dose (women of childbearing potential Only)

Exclusion Criteria

1. Uncontrolled grade 2 or greater toxicity except alopecia related to any prior treatment (i.e. chemotherapy, targeted therapy, radiation or surgery) within 7 days prior to first dose unless approved by the Medical Monitor
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 more than 150/100 mmHg
9. Concurrent participation in any other investigational study, unless non-interventional study and approved by Sponsor
10. Concurrent treatment with anticoagulation medication, except low molecular weight heparin, and approved by Sponsor
11. History of stroke, deep venous thrombosis (DVT), or transient ischemic attack (TIA), within 6 months prior to first dose
12. History of other cancer type, except for cutaneous basal cell or squamous cell carcinoma, or cervical in situ or very low/low risk prostate cancer, within the last 2 years prior to first dose.
13. Uncontrolled concurrent disease or illness including but not limited to:
a. symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
b. unstable or untreated cardiac conditions or ejection fraction of less than 50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
c. diabetes mellitus
d. coagulation disorder
e. psychiatric illness that would limit compliance with study requirements, as determined by the Investigator
14. History of severe hypersensitivity reaction to taxanes.
15. For Phase 2a Stage 2: treatment with a taxane within 6 months of first dose; advanced prostate cancer patients must be taxane-naive
16. Peripheral neuropathy
17. Other severe, acute, or chronic medical or psychiatric 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 & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the recommended Phase 2 dose (RP2D) of CRLX301 when administered by intravenous (IV) infusion once every 3-weeks or once a week dosing in patients with advanced solid tumor malignancies. This will be assessed by monitoring participants for dose-limiting adverse events (e.g. severely low white blood cell count, elevated liver function tests). [End of phase 1 (Dec2015- Jul2016)];To further establish the safety and tolerability of the CRLX301 MTD / RP2D. This will be assessed by monitoring participants adverse events, laboratory tests, vital signs and electrocardiogram. Examples of adverse events could include: decrease in white blood cells, decrease in red blood cells.[End of phase 2 (Jan 2017- July 2017). Patients will be monitored for 30 days post last dose of study drug. ]