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Castration Levels of TestosteronePhase 1/2NCT01505868

Cabazitaxel With or Without Carboplatin in Treating Patients With Previously Treated Metastatic Castration-Resistant Prostate Cancer

A Phase 1/2 study testing Cabazitaxel, Carboplatin and Laboratory Biomarker Analysis in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by M.D. Anderson Cancer Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This partially randomized phase I/II trial studies cabazitaxel with or without carboplatin in treating patients with previously treated prostate cancer that has spread to other areas of the body and does not respond to treatment with hormones. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Cabazitaxel, Carboplatin and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
2 sitesUnited States
Study dates
11 Jul 2012to 9 Dec 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Histologic evidence of prostate adenocarcinoma
  • In addition to patients with adenocarcinoma, patients with "anaplastic" features are also eligible as defined by at least one of the following: a) histologic evidence of small cell prostate cancer (patients with small cell carcinoma on histology are not required to demonstrate castration-resistant progression); b) any of the following metastatic presentations: (i) exclusive visceral metastases; (ii) radiographically predominant lytic bone metastases identified by plain X-ray or computed tomography (CT) scan; (iii) bulky (>= 5 cm in longest dimension) lymphadenopathy (iv) bulky (>= 5 cm) tumor mass in the prostate/pelvis (v) low PSA (=< 10 ng/ml) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases; (vi) elevated serum lactate dehydrogenase (LDH) (>= 2 x ULN) or elevated serum carcinoembryonic antigen (CEA) (>= 2 x upper limit of normal [ULN]) in the absence of other etiologies; (vii) short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapy
  • Castration-resistant prostate cancer; patients must have surgical or ongoing chemical castration (with luteinizing-hormone-releasing hormone [LHRH] agonists or LHRH antagonists), with a baseline testosterone level < 50 ng/dL
  • Metastatic disease; patients must have evidence for metastatic prostate cancer by bone scan and/or CT/magnetic resonance imaging (MRI) (i.e., soft tissue, visceral, lymph node); if lymph node, visceral and/or soft-tissue metastases are the only evidence of metastasis, at least one lesion must be >= 1.5 cm in diameter
  • Patients may have received prior treatment with androgen ablative therapies (such as bicalutamide, ketoconazole, diethylstilbestrol [DES], abiraterone, Xtandi, ARN-509) and/or "targeted" therapies (such as tyrosine kinase inhibitors); androgen ablative therapies must be discontinued >= 3 days prior to initiation of study treatment with the exception of abiraterone and/or enzalutamide, which may be continued during study treatment per the practice preference of the treating physician; patients who are predicted to benefit from an antiandrogen withdrawal response should be tested for this possibility before being considered for eligibility to this study; targeted therapies must be discontinued >= 2 weeks before initiation of study treatment
  • Both chemotherapy-naive and patients previously treated with chemotherapy are eligible; chemotherapy pretreated patients may have received a maximum of two prior systemic cytotoxic chemotherapies completed at least 3 weeks prior to initiation of study treatment
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  • Patients must have documented evidence of progressive disease as defined by any of the following: a) PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least >= 2.0 ng/mL; b) new or increasing non-bone disease (by Response Evaluation Criteria In Solid Tumors [RECIST]); c) positive bone scan with 2 or more new lesions (Prostate Cancer Working Group [PCWG2])
  • For purposes of stratification, patients will be categorized as "responders" or "non-responders" based on their response to prior docetaxel-based therapy; a) responders will have demonstrated objective responses to first-line docetaxel as determined by any of the following: 1. decrease in PSA level >= 50% from baseline, maintained for >= 6 weeks; 2. partial or complete response in lymph nodes and soft tissue metastases by RECIST; responders must have received >= 225 mg/m^2 (~ 3 cycles) of docetaxel; b) patients not meeting response criteria above will be considered as non-responders; we anticipate 2 general categories of non-responders based on the following disease phenotypes: 1. progressive disease on therapy without any objective evidence of response ("primary-resistant disease"); progressive disease on therapy with prior objective evidence of response, but response duration is =< 6 weeks ("docetaxel refractory disease"); non-responders are eligible even if they have received < 225 mg/m^2 of docetaxel
  • If present, peripheral neuropathy must be =< grade 2
  • Absolute neutrophil count (ANC) >= 1,500/ml (unless due to bone marrow infiltration by tumor in which case ANC >= 500/ml are allowed) (within 14 days before registration)
  • Platelets >= 100,000/ml (unless due to bone marrow infiltration by tumor in which case >= 50,000/ml are allowed) (within 14 days before registration)
  • Total bilirubin =< upper limit of normal with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome or if the patient has liver metastases and/or acute tumor-associated illness =< 4 x ULN (within 14 days before registration)
  • Serum glutamic-pyruvic transaminase (SGPT), (alanine aminotransferase [ALT]) AND/OR serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x the ULN or if patient has liver metastases and/or acute tumor-associated illness, =< 4 x ULN (within 14 days before registration)
  • Patient has creatinine clearance >= 30 ml/min using the Cockcroft-Gault equation (within 14 days before registration)
  • Men whose partner is a woman of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
  • Patient or his legally authorized representative must provide written informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Who cannot join

  • Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose
  • Samarium-153 within 28 days of registration, or strontium-89 within 12 weeks (84 days) of registration; patients who have received 2 or more doses of bone-seeking radioisotopes are not eligible
  • Current treatment on another therapeutic clinical trial
  • Prior treatment with cabazitaxel and/or carboplatin
  • Impending complication from bone metastases (fracture and/or cord compression); properly treated or stabilized fractures and/or cord compression is allowed
  • Presence of ongoing urinary obstruction (e.g., urinary retention, hydronephrosis) requiring medical intervention; properly treated urinary obstruction is allowed
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  • Patient has an uncontrolled intercurrent illness (e.g., uncontrolled diabetes, uncontrolled hypertension)
  • Patient has another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the patient's ability to provide informed consent or with the completion of treatment according to this protocol
  • Patients with a history of severe hypersensitivity reaction to JEVTANA® (cabazitaxel) or other drugs formulated with polysorbate 80
  • Patients with an active second malignancy that could, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: An Open Label Phase I/II Study of Cabazitaxel With or Without Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer

This partially randomized phase I/II trial studies cabazitaxel with or without carboplatin in treating patients with previously treated prostate cancer that has spread to other areas of the body and does not respond to treatment with hormones. Drugs used in chemotherapy, such as cabazitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cabazitaxel alone or with carboplatin is more effective in treating prostate cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dosage (MTD) of cabazitaxel-carboplatin in the phase I portion of the study.

II. To evaluate progression free survival achieved with cabazitaxel-carboplatin versus cabazitaxel alone in men with metastatic castration resistant prostate cancer (mCRPC) in the phase II portion of the study.

SECONDARY OBJECTIVES:

  1. To assess prostate-specific antigen (PSA) response rate (percentage of patients with > 50 % decline).

II. To correlate changes in bone specific alkaline phosphatase and urine n-telopeptides with response.

III. To evaluate overall survival. IV. To evaluate safety and toxicity. V. To evaluate influence of the anaplastic phenotype on response to therapy. VI. To collect and archive serum, plasma, and urine samples in study patients for later hypothesis generating associations.

OUTLINE: This is a phase I, dose-escalation study followed by a randomized phase II study.

PHASE I: Patients receive cabazitaxel intravenously (IV) over 60-90 minutes and carboplatin IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cabazitaxel IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cabazitaxel IV over 60-90 minutes and carboplatin IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months.

Being tested
Cabazitaxel, Carboplatin, Laboratory Biomarker Analysis
Medical subject headings
Lymphadenopathy, Prostatic Neoplasms

What participants receive

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

  • CabazitaxelDrug

    Also called Jevtana, RPR-116258A, Taxoid XRP6258, XRP-6258

    Given IV

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01505868
Study groupRoleWhat they receive
Arm I (cabazitaxel)ExperimentalPatients receive cabazitaxel IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cabazitaxel; Other: Laboratory Biomarker Analysis
Arm II (cabazitaxel and carboplatin)ExperimentalPatients receive cabazitaxel IV over 60-90 minutes and carboplatin IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cabazitaxel; Drug: Carboplatin; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Maximum Tolerated Dosage (MTD) of Cabazitaxel-carboplatin in the Phase I Portion of Study

    The MTD was defined as the highest dose cohort studied in which one of six or fewer patients experienced a dose-limiting toxicity.

    Measured: 6 months

  2. Progression Free Survival (PFS) of Cabazitaxel-carboplatin Versus Cabazitaxel in the Phase II Portion of Study

    PFS is the time from the first dose until progression of disease or death, whichever comes first. PFS times will be estimated using the Kaplan-Meier method.

    Measured: From the first dose until progression of disease or death, whichever comes first, up to 5 years

Secondary outcomes (5)

  1. Prostate Specific Antigen (PSA) Response Rate

    Percentage of participants with a greater than 50% decrease in measurable values of PSA during treatment from their baseline PSA.

    Measured: 5 years

  2. Bone-Specific Alkaline Phosphatase Response

    Percentage of participants with a greater than 50% decrease in measurable values of bone-specific alkaline phosphatase during treatment from their baseline values

    Measured: 5 years

  3. Urine N-Telopeptides Response

    Percentage of participants with a greater than 50% decrease in measurable values of urine n-telopeptides during treatment from their baseline values.

    Measured: 5 years

  4. Overall Survival (OS)

    Time from date of treatment start until date of death due to any cause or last follow up.

    Measured: Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years

  5. Phase II Most Common Grade 3-5 Adverse Events

    Grade 3: Serious reaction which requires medical treatment Grade 4: Life threatening. Grade 5 Death.

    Measured: Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years

Timeline

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

  1. First posted9 Jan 2012 (estimated)
  2. Study start11 Jul 2012
  3. Primary completion9 Dec 2019
  4. Study completion9 Dec 2019

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
170 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01505868
Sponsor's protocol ID
2011-0727
Other IDs
NCI-2012-00059, 2011-0727, P30CA016672
Status last verified
Jul 2021
First submitted
30 Dec 2011
Last updated
30 Jul 2021
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Corn PG, Heath EI, Zurita A, Ramesh N, Xiao L, Sei E, Li-Ning-Tapia E, Tu SM, Subudhi SK, Wang J, Wang X, Efstathiou E, Thompson TC, Troncoso P, Navin N, Logothetis CJ, Aparicio AM. Cabazitaxel plus carboplatin for the treatment of men with metastatic castration-resistant prostate cancers: a randomised, open-label, phase 1-2 trial. Lancet Oncol. 2019 Oct;20(10):1432-1443. doi: 10.1016/S1470-2045(19)30408-5. Epub 2019 Sep 9.

    PubMed 31515154

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cabazitaxel, Carboplatin and Laboratory Biomarker Analysis in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by M.D. Anderson Cancer Center at 2 sites 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 17 inclusion and 10 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: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Maximum Tolerated Dosage (MTD) of Cabazitaxel-carboplatin in the Phase I Portion of Study (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT01505868, which also lists 1 linked publication.

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 30 Jul 2021.

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