A Study of Radium-223 in Combination With Tasquinimod in Bone-only Metastatic Castration-Resistant Prostate Cancer

NCT02396368 | Withdrawn Phase 1 DMC

• 2 other identifiers: J1513IRB00058873
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/Ib study of Radium-223 in combination with Tasquinimod for patients with bone metastases from castration-resistant prostate cancer (CRPC). The investigators propose to determine the spectrum of tolerability of the combination of tasquinimod and radium-223 and determine a dose for a subsequent randomized phase II study (first cohort) and the proportion of men with bone-specific alkaline phosphatase response (second cohort).

Conditions

Prostate Cancer; Bone-only Metastatic Castration-Resistant Prostate Cancer (CRPC)

Keywords

Prostate cancer; Bone metastatic Castration-Resistant Prostate Cancer; Radium 223; Tasquinimod

Outcome Measures

Primary Outcomes (1)

• Safety of combining Radium-223 with tasquinimod

  Safety of combining Radium-223 with tasquinimod will be assessed by the incidence and severity of toxicities (adverse events and serious adverse events).

  Up to 18 months

Secondary Outcomes (9)

• Bone-ALP response

  Up to 18 months

• Time to radiographic or clinical progression or death, whichever comes first (progression free survival; PFS).

  Up to 18 months

• Time to first symptomatic SRE

  Up to 18 months

• Proportion of patients without symptomatic progression at 6 months

  6 months

• Median change in the bone scan index (BSI) within patients at 12 weeks compared to baseline bone scan.

  12 weeks

Other Outcomes (3)

• Radium-223 micro-scale dosimetry in bone tissue

  Up to 18 months

• The spatial distribution of Ra-223 in the patient's skeleton

  Up to 18 months

• The whole organ-level dosimetry of Ra-223 in the the patient's skeleton

  Up to 18 months

Study Arms (1)

Radium 223 and Tasquinimod

EXPERIMENTAL

During dose level 1, tasquinimod will start at 0.25mg/day orally with a goal of 0.5mg/day. Dose level 2 will start at 0.25mg/day with a goal of 1mg/day. Radium-223 will be administered per FDA-approved dosing (six IV injections at a dose of 50kBq/kg of body weight, administered every 4 weeks).

Drug: Tasquinimod; Radiation: Radium 223

Interventions

Tasquinimod DRUG

Tasquinimod is a quinoline-3-carboxamide analog that has demonstrated significant improvements in progression-free survival and overall survival in men with CRPC in a phase II trial.Tasquinimod will be administered at three dose levels (dose levels 1, 2, and -1). During dose level 1, tasquinimod will start at 0.25mg/day orally with a goal of 0.5mg/day. Dose level 2 will start at 0.25mg/day with a goal of 1mg/day. Dose level -1 will be 0.25mg/day without dose titration.

Radium 223 and Tasquinimod

Radium 223 RADIATION

Radium Ra 223 dichloride, an alpha particle-emitting pharmaceutical, is a radiotherapeutic drug. Radium 223 is supplied as a clear, colorless, isotonic, and sterile solution to be administered intravenously with pH between 6 and 8. Each milliliter of solution contains 1,000 kBq radium-223 dichloride (27 microcurie), corresponding to 0.53 ng radium-223, at the reference date. Radium is present in the solution as a free divalent cation.Radium-223 will be administered per FDA-approved dosing (six IV injections at a dose of 50kBq/kg of body weight, administered every 4 weeks).

Radium 223 and Tasquinimod

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age at least 18 years at the time of signing the ICF
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Two or more bone metastases (hot spots) confirmed by bone scintigraphy within 8 weeks prior to study entry
• Pain at baseline judged by the investigator to be related to bone metastases
• Known castration-resistant disease, defined according to PCWG2 criteria as:
• Castrate serum testosterone level: ≤50 ng/dL (≤1.7 nmol/L)
• Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through antiandrogen withdrawal prior to being eligible. The minimum timeframe to document failure of anti-androgen withdrawal will be four weeks
• Progressive disease based on PSA and/or radiographic criteria:Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least one week apart. Serum PSA at screening ≥ 2 ng/mL, Or Radiographic disease progression based on documented bone lesions by the appearance of two or more new lesions by bone scintigraphy
• Karnofsky Performance Status (KPS): ≥70% within 14 days before start of study treatment (ECOG ≤1)
• Life expectancy: at least 6 months
• Laboratory requirements:
• White Blood Cell (WBC) count ≥ 3 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x109/L
• Hemoglobin ≥10.0 g/dL

You may not qualify if:

• Has received an investigational therapeutic drug within the last 4 weeks prior to start of study treatment, or is scheduled to receive one during the treatment period.
• Has received external radiotherapy within the last 4 weeks prior to start of study treatment.
• Previous therapy with antiandrogens within 4 weeks (within 6 weeks for bicalutamide eg, Casodex®).
• Concurrent use of other anticancer agents or treatments, with the following exceptions:
• Ongoing treatment with LHRH agonists or antagonists, denosumab (Prolia) or bisphosphonate (eg, zoledronic acid) is allowed. Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed.
• Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment.
• Has received prior hemibody external radiotherapy.
• Has received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases.
• Has received blood transfusion or erythropoietin (EPO) within the last 4 weeks prior to start of study treatment.
• Has received prior treatment with Radium-223.
• Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.
• Symptomatic nodal disease, i.e. scrotal, penile or leg edema.
• Visceral metastases from CRPC (\>2 lung and/or liver metastases \[size ≥2cm\]), as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8 weeks prior to start of study treatment.
• Uncontrolled loco-regional disease.
• Other primary tumor (other than CRPC) including hematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

tasquinimod; radium Ra 223 dichloride

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Mario Eisenberger, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2015
• First Posted: March 24, 2015
• Study Start: March 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: November 20, 2015

Record last verified: 2015-11

Locations

US (1)