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

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01505868
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 170
• Locations: 2
• Arms: 2
• Actual Duration (Months): 88.9
• Patients Per Site: 85
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Lymphadenopathy; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma	Drug: Cabazitaxel; Drug: Carboplatin; Other: Laboratory Biomarker Analysis	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

2. 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).

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

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 170 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Phase I/II Study of Cabazitaxel With or Without Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer
• Actual Study Start Date: Jul 11, 2012
• Actual Primary Completion Date: Dec 9, 2019
• Actual Study Completion Date: Dec 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (cabazitaxel) 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.	Drug: Cabazitaxel; Given IV; Other Names: Jevtana RPR-116258A Taxoid XRP6258 XRP-6258 ; Other: Laboratory Biomarker Analysis; Correlative studies
Experimental: Arm II (cabazitaxel and carboplatin) 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.	Drug: Cabazitaxel; Given IV; Other Names: Jevtana RPR-116258A Taxoid XRP6258 XRP-6258 ; Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dosage (MTD) of Cabazitaxel-carboplatin in the Phase I Portion of Study [6 months]

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

2. Progression Free Survival (PFS) of Cabazitaxel-carboplatin Versus Cabazitaxel in the Phase II Portion of Study [From the first dose until progression of disease or death, whichever comes first, up to 5 years]

   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.

Secondary Outcome Measures

1. Prostate Specific Antigen (PSA) Response Rate [5 years]

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

2. Bone-Specific Alkaline Phosphatase Response [5 years]

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

3. Urine N-Telopeptides Response [5 years]

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

4. Overall Survival (OS) [Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years]

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

5. Phase II Most Common Grade 3-5 Adverse Events [Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

• 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

Exclusion Criteria:

• 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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
2	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Paul Corn, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 12, 2014

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01505868
• Other Study ID Numbers: 2011-0727; NCI-2012-00059; 2011-0727; P30CA016672
• First Posted: Jan 9, 2012
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Prostatic Neoplasms; Carcinoma, Small Cell; Small Cell Lung Carcinoma; Lymphadenopathy; Carboplatin

Study Results

Participant Flow

Recruitment Details	Participants were treated at MD Anderson Cancer Center in Houston, TX and Karmanos Cancer institute in Detroit, MI
Pre-assignment Detail	170 participants enrolled, 10 were phase I participants, 1 participant withdrew in phase I

Arm/Group Title	Phase I Cabazitaxel + Carboplatin Dose Zero	Phase I Cabazitaxel + Carboplatin Dose One	Phase I Cabazitaxel + Carboplatin Dose Two	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 20 mg/m2 and carboplatin area under the curve (AUC) 3 mg/mL per min every 21 days	Intravenous cabazitaxel 20 mg/m2 and carboplatin area under the curve (AUC) 4 mg/mL per min every 21 days	Intravenous cabazitaxel 25 mg/m2 and carboplatin area under the curve (AUC) 4 mg/mL per min every 21 days	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
Period Title: Overall Study
STARTED	4	3	3	79	81
COMPLETED	3	3	3	79	81
NOT COMPLETED	1	0	0	0	0

Baseline Characteristics

Arm/Group Title	Phase I Cabazitaxel + Carboplatin Dose Zero	Phase I Cabazitaxel + Carboplatin Dose One	Phase I Cabazitaxel + Carboplatin Dose Two	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin	Total
Arm/Group Description	Intravenous cabazitaxel 20 mg/m2 and carboplatin AUC 3 every 21 days up to 10 doses	Intravenous cabazitaxel 20 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses	Total of all reporting groups
Overall Participants	3	3	3	79	81	169
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	66	74	69	66	68	67
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	3 100%	3 100%	3 100%	79 100%	81 100%	169 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	0 0%	0 0%	4 5.1%	8 9.9%	13 7.7%
Not Hispanic or Latino	0 0%	0 0%	0 0%	12 15.2%	18 22.2%	30 17.8%
Unknown or Not Reported	2 66.7%	3 100%	3 100%	63 79.7%	55 67.9%	126 74.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	16 20.3%	8 9.9%	24 14.2%
White	3 100%	3 100%	3 100%	57 72.2%	64 79%	130 76.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	6 7.6%	9 11.1%	15 8.9%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	3 100%	79 100%	81 100%	169 100%
Eastern Cooperative Oncology Group (ECOG) performance status (Count of Participants)
Grade 0	1 33.3%	1 33.3%	1 33.3%	21 26.6%	22 27.2%	46 27.2%
Grade 1 and 2	2 66.7%	2 66.7%	2 66.7%	58 73.4%	59 72.8%	123 72.8%
Prostate-specific antigen (PSA) (µg/L) [Mean (Full Range) ]
Mean (Full Range) [µg/L]	380.4	89.5	217.6	23.7	33.8	28.75
Bone metastases (Count of Participants)
No	0 0%	0 0%	0 0%	7 8.9%	6 7.4%	13 7.7%
Yes	3 100%	3 100%	3 100%	72 91.1%	75 92.6%	156 92.3%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dosage (MTD) of Cabazitaxel-carboplatin in the Phase I Portion of Study
Description	The MTD was defined as the highest dose cohort studied in which one of six or fewer patients experienced a dose-limiting toxicity.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 25 mg/m2 and carboplatin area under the curve (AUC) 4 mg/mL per min every 21 days
Measure Participants	9
Number [mg/m^2]	25

2. Primary Outcome

Title	Progression Free Survival (PFS) of Cabazitaxel-carboplatin Versus Cabazitaxel in the Phase II Portion of Study
Description	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.
Time Frame	From the first dose until progression of disease or death, whichever comes first, up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
Measure Participants	79	81
Median (95% Confidence Interval) [months]	4.5	7.3

3. Secondary Outcome

Title	Prostate Specific Antigen (PSA) Response Rate
Description	Percentage of participants with a greater than 50% decrease in measurable values of PSA during treatment from their baseline PSA.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
Measure Participants	66	68
Number (95% Confidence Interval) [percentage of participants]	40.9 1363.3%	61.7 2056.7%

4. Secondary Outcome

Title	Bone-Specific Alkaline Phosphatase Response
Description	Percentage of participants with a greater than 50% decrease in measurable values of bone-specific alkaline phosphatase during treatment from their baseline values
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
Measure Participants	34	50
Number (95% Confidence Interval) [percentage of participants]	29.4 980%	62 2066.7%

5. Secondary Outcome

Title	Urine N-Telopeptides Response
Description	Percentage of participants with a greater than 50% decrease in measurable values of urine n-telopeptides during treatment from their baseline values.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
Measure Participants	20	24
Number (95% Confidence Interval) [percentage of participants]	55 1833.3%	62.5 2083.3%

6. Secondary Outcome

Title	Overall Survival (OS)
Description	Time from date of treatment start until date of death due to any cause or last follow up.
Time Frame	Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
Measure Participants	79	81
Median (95% Confidence Interval) [months]	17.3	18.5

7. Secondary Outcome

Title	Phase II Most Common Grade 3-5 Adverse Events
Description	Grade 3: Serious reaction which requires medical treatment Grade 4: Life threatening. Grade 5 Death.
Time Frame	Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Cabazitaxel	Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses	Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
Measure Participants	79	81
Fatique	9 300%	20 666.7%
Anemia	4 133.3%	23 766.7%
Neutropenia	4 133.3%	16 533.3%
Thrombocytopenia	1 33.3%	14 466.7%

8. Post-Hoc Outcome

Title	Aggressive Variant Prostate Carcinoma-Metastatic (ACPC-MS) Phenotypes Correlated to Response
Description	PFS and OS were reported for participants with and without AVPC-MS in the cabazitaxel vs cabazitaxel + carboplatin treatment groups
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AVPC-MS Postive	AVPC-MS Negative
Arm/Group Description	Immunochemistry positive for AVPC-MS	Immunochemistry negative for AVPC-MS
Measure Participants	26	30
Cabazitaxel PFS	1.7	6.3
Cabazitaxel + carboplatin PFS	7.5	6.5
Cabazitaxel OS	8.5	21.7
Cabazitaxel + carboplatin OS	20.2	21.5

Adverse Events

Time Frame	5 years
Arm/Group Title	Phase I Cabazitaxel + Carboplatin Dose Zero		Phase I Cabazitaxel + Carboplatin Dose One		Phase I Cabazitaxel + Carboplatin Dose Two		Phase II Cabazitaxel		Phase II Cabazitaxel + Carboplatin
Arm/Group Description	Intravenous cabazitaxel 20mg/m2 and carboplatin area under the curve (AUC) 3mg/mL per min every 21 days		Intravenous cabazitaxel 20 mg/m2 and carboplatin area under the curve (AUC) 4 mg/mL per min every 21 days		Intravenous cabazitaxel 25 mg/m2 and carboplatin area under the curve (AUC) 4 mg/mL per min every 21 days		Intravenous cabazitaxel 25 mg/m2 every 21 days up to 10 doses		Intravenous cabazitaxel 25 mg/m2 and carboplatin AUC 4 every 21 days up to 10 doses
All Cause Mortality
	Phase I Cabazitaxel + Carboplatin Dose Zero		Phase I Cabazitaxel + Carboplatin Dose One		Phase I Cabazitaxel + Carboplatin Dose Two		Phase II Cabazitaxel		Phase II Cabazitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		63/79 (79.7%)		69/81 (85.2%)
Serious Adverse Events
	Phase I Cabazitaxel + Carboplatin Dose Zero		Phase I Cabazitaxel + Carboplatin Dose One		Phase I Cabazitaxel + Carboplatin Dose Two		Phase II Cabazitaxel		Phase II Cabazitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		3/79 (3.8%)		4/81 (4.9%)
Gastrointestinal disorders
Diarrhea	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/79 (0%)	0	1/81 (1.2%)	1
Upper gastrointestinal hemorrhage	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	2	0/81 (0%)	0
General disorders
Fever	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/79 (0%)	0	1/81 (1.2%)	1
Investigations
WBC decreased	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/79 (0%)	0	1/81 (1.2%)	1
Metabolism and nutrition disorders
Hyponatremia	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	1	0/81 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	1	0/81 (0%)	0
Urinary tract infection	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/79 (0%)	0	1/81 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Phase I Cabazitaxel + Carboplatin Dose Zero		Phase I Cabazitaxel + Carboplatin Dose One		Phase I Cabazitaxel + Carboplatin Dose Two		Phase II Cabazitaxel		Phase II Cabazitaxel + Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		78/79 (98.7%)		81/81 (100%)
Blood and lymphatic system disorders
Anemia	2/3 (66.7%)		1/3 (33.3%)		3/3 (100%)		20/79 (25.3%)	31	47/81 (58%)	112
Ear and labyrinth disorders
Vertigo	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/79 (1.3%)	1	1/81 (1.2%)	1
Gastrointestinal disorders
Gastrointestinal disorders	0/3 (0%)		0/3 (0%)		0/3 (0%)		4/79 (5.1%)	7	7/81 (8.6%)	8
Constipation	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		14/79 (17.7%)	23	35/81 (43.2%)	58
Diarrhea	0/3 (0%)		3/3 (100%)		2/3 (66.7%)		44/79 (55.7%)	102	54/81 (66.7%)	160
Dyspepsia	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	1	1/81 (1.2%)	1
Mucositis oral	0/3 (0%)		0/3 (0%)		0/3 (0%)		6/79 (7.6%)	11	7/81 (8.6%)	14
Nausea	0/3 (0%)		2/3 (66.7%)		2/3 (66.7%)		28/79 (35.4%)	60	57/81 (70.4%)	170
Pain	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		7/79 (8.9%)	14	9/81 (11.1%)	9
Vomiting	0/3 (0%)		2/3 (66.7%)		0/3 (0%)		14/79 (17.7%)	25	30/81 (37%)	63
General disorders
Edema limbs	1/3 (33.3%)		1/3 (33.3%)		1/3 (33.3%)		11/79 (13.9%)	13	10/81 (12.3%)	13
Fatigue	1/3 (33.3%)		3/3 (100%)		3/3 (100%)		58/79 (73.4%)	125	69/81 (85.2%)	272
Fever	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		5/79 (6.3%)	5	9/81 (11.1%)	14
Flu like symptoms	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	1	6/81 (7.4%)	8
Localized Edema	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	1	3/81 (3.7%)	3
Malaise	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	1	8/81 (9.9%)	9
Non-cardiac cest pain	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		4/79 (5.1%)	5	1/81 (1.2%)	1
Injury, poisoning and procedural complications
Bruising	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/79 (1.3%)	1	2/81 (2.5%)	2
Investigations
Alanine aminotransferase increased	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		4/79 (5.1%)	4	4/81 (4.9%)	4
Alkaline phosphatase increased	2/3 (66.7%)		0/3 (0%)		0/3 (0%)		3/79 (3.8%)	3	4/81 (4.9%)	4
Aspartate aminotransferase increased	0/3 (0%)		0/3 (0%)		0/3 (0%)		5/79 (6.3%)	5	12/81 (14.8%)	14
Creatinine increased	0/3 (0%)		1/3 (33.3%)		2/3 (66.7%)		7/79 (8.9%)	8	8/81 (9.9%)	11
Lymphocyte count decreased	0/3 (0%)		0/3 (0%)		0/3 (0%)		9/79 (11.4%)	17	8/81 (9.9%)	19
Neutrophil count decreased	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		6/79 (7.6%)	7	16/81 (19.8%)	32
Platelet count decreased	2/3 (66.7%)		1/3 (33.3%)		0/3 (0%)		5/79 (6.3%)	7	32/81 (39.5%)	83
Weight loss	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		4/79 (5.1%)	5	12/81 (14.8%)	14
WBC decreased	0/3 (0%)		0/3 (0%)		0/3 (0%)		8/79 (10.1%)	11	24/81 (29.6%)	50
Metabolism and nutrition disorders
Anorexia	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		7/79 (8.9%)	7	17/81 (21%)	21
Dehydration	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		4/79 (5.1%)	4	8/81 (9.9%)	12
Hypercalcemia	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/79 (1.3%)	1	2/81 (2.5%)	2
Hyperglycemia	1/3 (33.3%)		1/3 (33.3%)		1/3 (33.3%)		14/79 (17.7%)	17	16/81 (19.8%)	24
Hyperkalemia	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		3/79 (3.8%)	3	6/81 (7.4%)	11
Hypernatremia	0/3 (0%)		0/3 (0%)		0/3 (0%)		6/79 (7.6%)	7	4/81 (4.9%)	4
Hypoalbuminemia	2/3 (66.7%)		0/3 (0%)		0/3 (0%)		3/79 (3.8%)	3	5/81 (6.2%)	5
Hypocalcemia	2/3 (66.7%)		0/3 (0%)		0/3 (0%)		5/79 (6.3%)	6	10/81 (12.3%)	18
Hypokalemia	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		7/79 (8.9%)	9	13/81 (16%)	31
Hypomagnesenia	2/3 (66.7%)		2/3 (66.7%)		1/3 (33.3%)		6/79 (7.6%)	7	35/81 (43.2%)	51
Hyponatrenia	0/3 (0%)		0/3 (0%)		0/3 (0%)		4/79 (5.1%)	5	6/81 (7.4%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/79 (1.3%)	1	1/81 (1.2%)	1
Bone pain	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		2/79 (2.5%)	2	7/81 (8.6%)	8
Chest wall pain	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/79 (0%)	0	1/81 (1.2%)	1
Flank pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		4/79 (5.1%)	10	3/81 (3.7%)	3
Genralized muscle weakness	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	2	5/81 (6.2%)	7
Myalgia	0/3 (0%)		0/3 (0%)		0/3 (0%)		4/79 (5.1%)	4	4/81 (4.9%)	6
Nervous system disorders
Dizziness	0/3 (0%)		0/3 (0%)		2/3 (66.7%)		6/79 (7.6%)	6	13/81 (16%)	16
Dysgeusia	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		11/79 (13.9%)	11	16/81 (19.8%)	22
Headache	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		6/79 (7.6%)	10	7/81 (8.6%)	7
Paresthesia	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		8/79 (10.1%)	10	15/81 (18.5%)	18
Neuropathy	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		5/79 (6.3%)	8	16/81 (19.8%)	23
Presyncope	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/79 (1.3%)	1	2/81 (2.5%)	2
Psychiatric disorders
Anxiety	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		2/79 (2.5%)	2	3/81 (3.7%)	4
Insomnia	0/3 (0%)		0/3 (0%)		0/3 (0%)		5/79 (6.3%)	6	2/81 (2.5%)	2
Renal and urinary disorders
Cystitis noninfective	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		2/79 (2.5%)	2	4/81 (4.9%)	5
Hematuria	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		3/79 (3.8%)	4	10/81 (12.3%)	14
Hemoglobinuria	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/79 (1.3%)	1	5/81 (6.2%)	5
Proteinuria	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		1/79 (1.3%)	1	6/81 (7.4%)	7
Urinary urgency	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/79 (1.3%)	1	0/81 (0%)	0
Urinary frequency	0/3 (0%)		0/3 (0%)		0/3 (0%)		4/79 (5.1%)	4	1/81 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		2/79 (2.5%)	3	4/81 (4.9%)	6
Dyspnea	1/3 (33.3%)		1/3 (33.3%)		2/3 (66.7%)		19/79 (24.1%)	34	34/81 (42%)	71
Epitaxis	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/79 (1.3%)	2	6/81 (7.4%)	8
Skin and subcutaneous tissue disorders
Alopecia	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		14/79 (17.7%)	14	24/81 (29.6%)	26
Rash	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		3/79 (3.8%)	4	8/81 (9.9%)	11
Vascular disorders
Flushing	0/3 (0%)		0/3 (0%)		0/3 (0%)		3/79 (3.8%)	5	4/81 (4.9%)	4
Hot flashes	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		3/79 (3.8%)	3	4/81 (4.9%)	4
Hypotension	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		2/79 (2.5%)	3	6/81 (7.4%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.