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Prostate CancerPhase 1Radium-223NCT02396368

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

A Phase 1 study testing Tasquinimod and Radium 223 in people with Prostate Cancer and Bone-only Metastatic Castration-Resistant Prostate Cancer (CRPC), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Tasquinimod and Radium 223
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Mar 2015to Jul 2017
Phase
Phase 1
Are there results?
None posted in the registry

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
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Total bilirubin ≤ 1.5 x ULN
  • AST and ALT ≤ 3 x ULN
  • Creatinine ≤ 1.5 x ULN
  • If sexually active with partner of childbearing potential, patient will agree to use adequate contraceptive methods (barrier contraceptive with spermicide or vasectomy) while on study drug. The adequate contraceptive method should be continued for 6 months after the last dose of radium-223 or 14 days after the last dose of tasquinimod, whichever comes later.
  • No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin).
  • Able to swallow and retain oral medication.
  • The subject is willing and able to comply with the protocol, and agrees to return to the hospital for follow-up visits and examination
  • The subject has been fully informed about the study and has signed the informed consent form and, where appropriate, HIPAA authorization for release of personal health information

Who cannot join

  • 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.
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  • 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).
  • Ongoing treatment with warfarin unless the international normalized ratio is well controlled and below 4. Treatment with other anticoagulants is allowed.
  • Maintenance treatment with corticosteroids corresponding to a prednisolone or prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days.
  • Systemic exposure to ketoconazole or other strong CYP3A4 isozyme inhibitors or inducers (Appendix A) within 14 days prior to the start of study treatment. Systemic exposure to amiodarone is not allowed within 1 year prior to the start of study treatment.
  • Ongoing treatment with sensitive CYP1A2 substrate or CYP1A2 substrate with narrow therapeutic range (Appendix A) at the start of study treatment.
  • Ongoing treatment with CYP3A4 substrate with narrow therapeutic range (Appendix A) at the start of study treatment.
  • Has imminent or established spinal cord compression based on clinical findings and/or MRI.
  • Any other serious illness or medical condition that would, in the opinion of the investigator, make this protocol unreasonably hazardous, including, but not limited to:
  • Any uncontrolled infection
  • Cardiac failure NYHA (New York Heart Association) III or IV
  • Crohn's disease or ulcerative colitis
  • Bone marrow dysplasia
  • Known allergy to any of the compounds under investigation
  • Unmanageable fecal incontinence

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21205

Other trials in United States

About this study

Official title: A Phase I/Ib Study of Radium-223 in Combination With Tasquinimod in Bone-only Metastatic Castration-Resistant Prostate Cancer

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).

Read the detailed description

This is a study of Radium-223 in combination with Tasquinimod. The target population is patients with bone metastases from castration-resistant prostate cancer intended for treatment with radium-223.

After baseline assessment, all subjects will receive six cycles of Radium-223 separated by an interval of 28 days. 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). The treatment maintenance dose of tasquinimod will be a maximum of 1 mg of tasquinimod taken once daily with water (~200 mL). The initial target dose of tasquinimod is 0.5mg/day. All subjects will be followed up for 12 months after start of study treatment.

The investigators propose a phase I/Ib trial of the addition of tasquinimod to FDA-approved doses of radium-223 in men with symptomatic bone-only metastatic CRPC. The investigators anticipate that given their distinct mechanisms of action and non-overlapping toxicity profiles that additive or synergistic toxicity would be minimal. The investigators hypothesize that adding tasquinimod to radium therapy may result in improved measures of efficacy including reduction in total alkaline phosphatase, time to first skeletal-related event and PSA and radiographic progression-free survival.

In the Phase I portion of dose-escalation scheme, the dose escalation will follow a 3+3 design with intra-patient dose-escalation from 0.25mg/day of tasquinimod to a goal dose of either 0.25mg (dose-level -1), 0.5mg (dose-level 1), or 1.0mg/day (dose-level 2) based on individual tolerability.

Upon identifying a recommended Phase II combination dose-level of Radium-223 and tasquinimod, the investigators will move to the Phase Ib portion and open an expanded cohort of up to 35 additional patients to achieve a total of 38 patients treated at the recommended phase II dose-level (including those from the dose-escalation phase).

Being tested
Tasquinimod, Radium 223
Keywords
Prostate cancer, Bone metastatic Castration-Resistant Prostate Cancer, Radium 223, Tasquinimod
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • TasquinimodDrug

    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 223Radiation

    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).

Study groups in NCT02396368
Study groupRoleWhat they receive
Radium 223 and TasquinimodExperimentalDuring 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).
Receives: Drug: Tasquinimod; Radiation: Radium 223

What is being measured

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

  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).

    Measured: Up to 18 months

Secondary outcomes (9)

  1. Bone-ALP response

    Bone-specific alkaline phosphatase (serum bone markers) response will be described as percentage of change from baseline to 6 months or earlier for those who discontinue study therapy

    Measured: Up to 18 months

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

    Time to radiographic or clinical progression or death, whichever comes first (progression free survival; PFS). Based on RECIST version 1.1 and Prostate Cancer Working Group 2 (PCWG2) definitions including:

    1. Progression of soft tissue lesions according to RECIST 1.1
    2. Progression of bone lesions detected with bone scan according to PCWG2 criteria
    3. Radiologically-confirmed spinal cord compression or pathological fracture due to malignant progression
    4. Either of: time to first symptomatic SRE or symptomatic progression.

    Measured: Up to 18 months

  3. Time to first symptomatic SRE

    Time to first symptomatic SRE (defined as first use of XRT to relieve skeletal symptoms, new pathologic vertebral or nonvertebral bone fractures, spinal cord compression, or tumor -related orthopedic surgical intervention).

    Measured: Up to 18 months

  4. Proportion of patients without symptomatic progression at 6 months

    To determine proportion of patients without symptomatic progression at 6 months, defined as any one or more of:

    1. Regular consumption of narcotic analgesics (single IV dose or >10 of 14 days of oral narcotic use)
    2. Requirement for radiation therapy for control of tumor-related pain
    3. VAS pain rating of >4 due to cancer pain on two consecutive ratings

    Measured: 6 months

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

    Measured: 12 weeks

  6. PSA decline will be reported on all patients

    The percentage of change in PSA from baseline to 12 weeks.

    Measured: 12 weeks

  7. PSA progression (PSA progression free survival; PSA-PFS)

    PSA progression (PSA progression free survival; PSA-PFS) will be defined per the PCWG2 guidelines

    1. For those subjects showing an initial decline in PSA from baseline, is defined as an increase in PSA that is ≥25% and ≥2 ng/mL above the nadir, and which is confirmed by a second value 3 or more weeks later (i.e., a confirmed rising trend).
    2. For those subjects with no decline in PSA from baseline, is defined as an increase in PSA that is ≥25% and ≥2 ng/mL after 12 weeks.

    Measured: Up to 18 months

  8. Time to death after start of study treatment months

    Time to death after start of study treatment (overall survival; OS)

    Measured: Up to 18 months

  9. Changes in bone markers

    Changes in other bone markers:

    1. Serum C-telopeptide(uCTX-1)
    2. N-terminal propeptide of procollagen type 1 (P1NP)

    Measured: Up to 18 months

Timeline

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

  1. First posted24 Mar 2015 (estimated)
  2. Study startMar 2015
  3. Primary completionJul 2017 (estimated)
  4. Study completionJul 2017 (estimated)

Why it stopped: Phase III study results for the drug Tesquinimod were not promising so it was a drug development decision to stop using the drug

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02396368
Sponsor's protocol ID
J1513
Other IDs
IRB00058873
Acronym
Radium-223
Status last verified
Nov 2015
First submitted
25 Feb 2015
Last updated
20 Nov 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tasquinimod and Radium 223 in people with Prostate Cancer and Bone-only Metastatic Castration-Resistant Prostate Cancer (CRPC), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site 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 23 inclusion and 28 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: withdrawn, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Safety of combining Radium-223 with tasquinimod (time frame: Up to 18 months). 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 NCT02396368.

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 20 Nov 2015.

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