The CATCH Prostate Cancer Trial: Cabazitaxel And Tasquinimod in Men With Prostate Cancer (CATCH)

The CATCH Prostate Cancer Trial: Cabazitaxel And Tasquinimod in Men With Castration-Resistant Heavily Pre-treated Prostate Cancer

The standard of care for men with metastatic CRPC in 2010 following progression on docetaxel is cabazitaxel or abiraterone acetate/prednisone. Based on results from two other studies, cabazitaxel and prednisone has become a standard second line chemotherapy regimen and becomes the backbone upon which to improve upon. Thus, the primary objective of this study is to determine the recommended dose of tasquinimod in combination with cabazitaxel and prednisone based on safety and tolerability in men with chemorefractory metastatic castration-resistant prostate cancer (CRPC).

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: tasquinimod; Drug: tasquinimod 0.25 mg; 0.5 mg; Drug: tasquinimod 0.25 mg; 0.5 mg; 1.0 mg

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features;
2. At least 18 years of age when signing the Informed Consent;
3. Presence of metastatic disease on bone scan or CT/MRI imaging;
4. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., medical or surgical castration);
5. For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial;
6. Serum testosterone level < 50 ng/dL at the Screening Visit;
7. Progressive disease on or following docetaxel-based chemotherapy with medical or surgical castration. Patients who are intolerant of docetaxel are also allowed. Disease progression for study entry is defined as one or more of the following three criteria: 1) PSA progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥ 2 μg/L (2 ng/mL); 2) Soft tissue disease progression defined by RECIST 1.1; 3) Bone metastatic disease progression defined by one or more new lesions on bone scan that are not clinically consistent with tumor flare;
8. No more than three prior chemotherapy regimens with at least one regimen containing docetaxel (unless intolerant as per # 7 above);
9. Karnofsky Performance Status of >70;
10. Estimated life expectancy of at least three months;
11. Able to swallow the study drug and comply with study requirements;
12. Willing and able to give informed consent.

Exclusion Criteria:

1. Subjects > 80 years old (dose escalation phase only, due to lower clearance in elderly patients);
2. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment;
3. Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed provided follow up imaging documents stability of epidural disease);
4. Absolute neutrophil count < 1,200/μL, platelet count < 100,000/μL, and hemoglobin <9 g/dL at the Screening Visit; (NOTE: patients may not have received any growth factors or blood transfusions within seven days of the hematologic laboratory values obtained at the Screening Visit)
5. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 times the upper limit of normal at the Screening Visit;
6. Creatinine > 1.5 x ULN at the Screening visit;
7. History of another malignancy within the previous 3 years other than non-melanomatous skin cancer or non-invasive bladder cancer treated with curative intent;
8. Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide, MDV3100), 5-α reductase inhibitors (finasteride, dutasteride), estrogens (ie DES), sipuleucel-T, or chemotherapy within 28 days of Day 1 visit or plans to initiate treatment with any of these treatments during the study;
9. Use of herbal products that may decrease PSA levels or systemic corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within four weeks of Day 1 visit;
10. Ongoing treatment with warfarin unless the international normalized ratio (INR) is well controlled and below 4
11. Exposure to ketoconazole or other strong CYP3A4 inhibitors or inducers intravenously or orally within 28 days prior to Day 1 Visit. For abiraterone acetate or TAK700, 14 days washout is needed.
12. Ongoing treatment with sensitive CYP1A2 substrates or CYP1A2 substrates with narrow therapeutic range (Appendix 3).
13. Ongoing treatment with CYP3A4 substrates with narrow therapeutic range (Appendix 3).
14. Radiation therapy within 2 weeks (if single fraction of radiotherapy within 2 weeks) and radionuclide therapy within 8 weeks of Day 1 visit;
15. Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery;
16. Structurally unstable bone lesions suggesting impending fracture;
17. Clinically significant cardiovascular disease including:myocardial infarction within 6 months, uncontrolled angina within 3 months, congestive heart failure, Diagnosed or suspected congenital long QT syndrome; significant ventricular arrhythmias, Prolonged corrected QT interval by the Fridericia or Bazett correction formula, History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place; Hypotension (systolic blood pressure < 86 mMHg or bradycardia with a heart rate < 50 beats per minute on any ECG taken at the Screening or Day 1 visit; Uncontrolled hypertension; TIA or stroke/CVA within 6 months of Day 1 visit; Rest limb claudication or ischemia within 6 months of Day 1 visit
18. Use of an investigational agent within four weeks of Day 1 visit or plans to initiate treatment with an investigational agent during the study;
19. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last three months);
20. Major surgery within four weeks prior to Day 1 visit.
21. Presence of NCI CTC grade >1 peripheral neuropathy
22. History of pancreatitis
23. Known positive serology for HIV (patients with known history of HIV will be excluded because of potential for unforeseen toxicity and morbidity in an immunocompromised host).
24. Chronic hepatitis B or C with advanced, decompensated hepatic disease, or cirrhosis of the liver or history of a chronic viral hepatitis or known viral hepatitis carrier (patients recovered from hepatitis will be allowed to enter the study).
25. Documented prior disease progression on tasquinimod -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tasquinimod single dose	Drug: tasquinimod; tasquinimod 0.25 mg continuously
Experimental: tasquinimod 0.25 mg followed by 0.5 mg; tasquinimod 0.25 mg for 3 weeks followed by 0.5 mg continuously, if tolerated	Drug: tasquinimod 0.25 mg; 0.5 mg; tasquinimod 0.25 mg for 3 weeks followed by 0.5 mg continuously, if tolerated
Experimental: tasquinimod 0.25 mg; 0.5 mg; 1.0 mg; tasquinimod 0.25 mg for 3 weeks followed by 0.5 mg for 3 weeks followed by 1.0 mg continuously, if tolerated	Drug: tasquinimod 0.25 mg; 0.5 mg; 1.0 mg; tasquinimod 0.25 mg for 3 weeks followed by 0.5 mg for 3 weeks followed by 1.0 mg continuously, if tolerated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who experience dose limiting toxicities at the highest titrated dose for each dose level	The primary objective is to determine the recommended dose of tasquinimod in combination with cabazitaxel and prednisone based on safety and tolerability in men with chemorefractory metastatic castration-resistant prostate cancer (CRPC).	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of progression free survival	Preliminary evidence of durable efficacy will be based on a modified PCWG2-defined radiologic progression-free survival including RECIST 1.1 criteria (PFS).	Every 9 weeks
Evaluation of overall response	Radiologic response criteria using RECIST 1.1 (overall response)	Every 9 weeks
Preliminary evidence of response efficacy as measured by the rates of PSA decline (waterfall plot) and benchmarks of reaching a >30% decline within 3 months, a PSA decline >50% and >90%, and PSA normalization. Duration of PSA responses will be measured		Every 3 weeks
Favorable changes in circulating tumor cell number (5 or greater to less than 5) and proportion of men who achieve a reduction in CTC count		Every 3 weeks
Number and percent of participants that are alive	Overall survival	2 years
Detailed characterization of all NCI CTC v4.0 toxicities over time (per cycle)	Detailed characterization of all NCI CTC v4.0 toxicities over time (per cycle)	Every 3 weeks
The concentration of tasquinimod and cabazitaxel in blood plasma	Pharmacokinetic analysis of tasquinimod and cabazitaxel (cycle 1-4 only)	12 weeks
Pain response, as measured by percentage of patients with a reduction of at least 2 points on the visual analog scale despite a stable pain regimen. Pain scores over time will be described in an exploratory fashion.		Every 3 weeks
Changes in bone alkaline phosphatase and LDH over time	Descriptive statistics will be used to summarize laboratory variables	Every 3 weeks

Collaborators and Investigators

• Sponsor: Andrew J. Armstrong, MD
• Investigators: Principal Investigator: Andrew Armstrong, MD, Duke Cancer Institute

Publications and helpful links

Helpful Links

• Duke Cancer Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: January 17, 2012
• First Submitted That Met QC Criteria: January 17, 2012
• First Posted (Estimate): January 20, 2012

Study Record Updates

• Last Update Posted (Actual): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Pro00032421; c11-082 (Other Grant/Funding Number: PCCTC)