Docetaxel and Prednisone With or Without Vaccine Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01145508
• Collaborator: (none)
• Enrollment: 10
• Locations: 14
• Arms: 2
• Duration (Months): 62
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well docetaxel and prednisone with or without vaccine therapy works in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Drugs used in chemotherapy, such as docetaxel and prednisone, 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. Vaccines made from an antigen may help the body build an effective immune response to kill tumor cells. It is not yet known whether docetaxel and prednisone are more effective with or without vaccine therapy in treating prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Hormone-Resistant Prostate Cancer; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer	Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Drug: Prednisone; Biological: Recombinant Fowlpox-PSA(L155)/TRICOM Vaccine; Biological: Rilimogene Galvacirepvec	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the overall survival in patients treated with PSA-TRICOM (fowlpox-PSA-TRICOM vaccine and rilimogene-galvacirepvec) and docetaxel chemotherapy versus docetaxel chemotherapy only.

SECONDARY OBJECTIVES:

1. To evaluate the time to radiographic progression after beginning docetaxel chemotherapy in patients previously treated with PSA-TRICOM vaccine versus those not treated with this vaccine.

2. To compare objective responses (according to Response Evaluation Criteria in Solid Tumors [RECIST]) between the two treatment groups in those patients with measurable disease.

3. To evaluate prostate-specific antigen (PSA) response rates (decline >= 50%) in patients treated with PSA-TRICOM and docetaxel chemotherapy versus docetaxel chemotherapy only.

4. To evaluate immune responses elicited in patients treated before and after docetaxel chemotherapy.

5. To evaluate the association between development of prostate antigen-specific immune responses and time to progression and overall survival.

6. To evaluate the association of predicted survival (by Halabi nomogram) with actual survival in patients treated with PSA-TRICOM vaccine versus those not treated with this vaccine.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A (vaccine and chemotherapy): Patients receive rilimogene-galvacirepvec subcutaneously (SC) on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel intravenously (IV) over 1 hour on day 1 and prednisone orally (PO) twice daily (BID) on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

ARM B (chemotherapy): Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Trial of Docetaxel With or Without PSA-TRICOM Vaccine in Patients With Castrate-Resistant Metastatic Prostate Cancer
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (vaccine therapy and chemotherapy) Patients receive rilimogene-galvacirepvec SC on day 1 of course 1 and fowlpox-PSA-TRICOM vaccine SC on days 15, 29, 43, and 57 of course 1. Beginning on day 85 (day 1 of course 2), patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: Docetaxel; Given IV; Other Names: Docecad RP56976 Taxotere Taxotere Injection Concentrate ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Prednisone; Given PO; Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone ; Biological: Recombinant Fowlpox-PSA(L155)/TRICOM Vaccine; Given SC; Other Names: PROSTVAC-F rFowlpox-PSA(L155)/TRICOM Vaccine ; Biological: Rilimogene Galvacirepvec; Given SC; Other Names: PROSTVAC Prostvac-V Recombinant Vaccinia-PSA(L155)-TRICOM Vaccine Recombinant Vaccinia-PSA(L155)/TRICOM Recombinant Vaccinia-PSA(L155)/TRICOM Vaccine rVaccinia-Prostate-Specific Antigen/TRICOM Vaccine rVaccinia-PSA(L155)-TRICOM Vaccine
Active Comparator: Arm B (docetaxel, prednisone) Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO BID on days 1-21. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Drug: Docetaxel; Given IV; Other Names: Docecad RP56976 Taxotere Taxotere Injection Concentrate ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Prednisone; Given PO; Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Assessed every 3 months for 2 years, and then every 6 months for 3 years]

   Overall survival is defined as the time from randomization to death or the date of last known alive.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient must have histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)

• Patient must have metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (computed tomography [CT] of abdomen/pelvis, bone scintigraphy)

• Patient must have castrate-resistant disease, defined as follows:

• Patient must have received standard of care androgen deprivation treatment (ADT) before trial entry (surgical castration versus gonadotropin-releasing hormone [GnRH] analogue or antagonist treatment); subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study

• Patient must have been treated previously with a nonsteroidal antiandrogen, with evidence of subsequent disease progression; subjects must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to randomization; subjects who demonstrate an anti-androgen withdrawal response, defined as a >= 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal

• Patient must have castration levels of testosterone (< 50 ng/dL) within 4 weeks prior to randomization

• Patient must have progressive disease while receiving ADT as defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria:

• PSA: at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value >= 2.0 ng/mL

• Measurable disease: >= 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions by RECIST criteria version 1.1; the greatest diameter of a target lesion must be at least 1.0 cm by CT scan (1.5 cm in shortest axis for lymph nodes)

• Non-measurable (bone) disease: the appearance of two or more new areas of uptake on bone scan consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging [MRI])

• Patient must not have poor prognosis features suggested by the following required information:

• Presence of visceral (non-lymph node, non-bone) metastases

• Poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status [PS] of 2 or greater)

• Alkaline phosphatase (IU/L) > 2 x institutional upper limit of normal

• Lactate dehydrogenase (LDH) (U/L) > 2 x institutional upper limit of normal

• Patient must have an ECOG performance status of 0 or 1

• White blood cell (WBC) count >= 2000/mm^3

• Absolute neutrophil count (ANC) >= 1500/mm^3

• Platelet count >= 100,000/mm^3

• Creatinine =< 2.0 mg/dL

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x institutional upper limit of normal (ULN)

• Total bilirubin < institutional upper limit of normal (ULN)

• Patient must have completed any prior treatments (apart from androgen deprivation as previously described) >= 4 weeks prior to randomization and have recovered (to < grade

1. from any acute toxicities attributed to this prior treatment

• Patient must agree to use an accepted and effective method of contraception prior to study entry and for the duration of study participation (or at least 4 months after the last vaccination in subjects receiving vaccine series); if patient impregnates a woman while participating in this study, he should inform his treating physician immediately

• Patient must not be receiving any other investigational agents or be receiving concurrent anticancer therapy other than ADT

• Patient must not have been treated with a prior anti-cancer vaccine (including sipuleucel-T, Provenge®)

• Patient must not have received treatment with any of the following medications within 4 weeks of randomization or while on study:

• Systemic corticosteroids (excluding prednisone and dexamethasone administered as part of study protocol); inhaled, intranasal or topical corticosteroids are acceptable; steroid eye drops are contraindicated however, for 2 weeks prior to vaccination and for at least 4 weeks after vaccinia vaccination

• PC-SPES

• Saw palmetto

• Megestrol

• Ketoconazole

• 5-alpha-reductase inhibitors - patients already taking 5-alpha-reductase inhibitors prior to 28 days prior to randomization may stay on these agents throughout the course of therapy, but these should not be started while patients are on study

• Diethyl stilbestrol

• Any other hormonal agent or supplement with possible anti-cancer activity

• Patient must not have been treated with external beam radiation therapy within 4 weeks of randomization

• Patient must not have received prior radiation therapy to > 30% of bone marrow

• Patient must not have had surgery within 4 weeks of randomization

• Patient must not have received prior chemotherapy within 6 months of randomization; prior and/or concurrent treatment with bisphosphonates, however, is permitted

• Patient must not have received prior chemotherapy for metastatic prostate cancer

• Patient cannot have a known history of human immunodeficiency virus (HIV) 1 or 2, human T-lymphotropic virus (HTLV)-1, hepatitis B, or hepatitis C (or any other potentially immunosuppressive infection); eligible subjects must have negative serologic testing for HIV, hepatitis B surface antigen, and hepatitis C

• Patient cannot have a history of autoimmune disease requiring active immunosuppressive therapy or have organ dysfunction >= grade 2 as a result of known autoimmune disease; eligible subjects must have antinuclear antibodies (ANA) titer < 1:320

• Patient must not have undergone splenectomy

• Patient must not have other active malignancies other than non-melanoma skin cancers or carcinoma in situ of the bladder; subjects with a history of other cancers who have been adequately treated and have been recurrence-free for >= 3 years are eligible

• Patient cannot have a known allergy to eggs

• Patient cannot have a known intolerance or allergic reactions to docetaxel or compounds of similar chemical or biologic composition

• Patient cannot have a known history of allergy or intolerable reaction to a previous vaccinia virus vaccination (e.g., smallpox)

• Patient or close household contacts of patient (those who share housing or have close physical contact with the patient) cannot have close physical contact to persons with the following conditions within 3 weeks after potential vaccinia immunization:

• A history of eczema, active eczema or other acute, chronic or exfoliative skin conditions, including Darier's disease (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or open wounds)

• Pregnant or nursing women

• Children under 3 years of age

• Immunodeficient or immunosuppressed persons (e.g. HIV, or treated for other diseases with immunosuppressive agents)

• Any other moderate or severe acute illness until the illness resolves Patients who would be unable to avoid these conditions for a 3-week period are not eligible; patients should also refer to the patient instruction sheet for vaccinia virus

• Patient cannot have known brain metastases

• Patient cannot have a known history of recent (within 6 months) stroke, myocardial infarction, unstable angina, New York Heart Association class II-IV congestive heart failure, or significant cardiomyopathy requiring treatment

• Patient cannot take known strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) within 2 weeks of beginning docetaxel through its discontinuation; substrates of CYP3A4 with a narrow therapeutic/toxicity window may be used with caution, with prior approval of the study chair or institution's principal investigator (PI)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
2	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
3	Northwestern University	Chicago	Illinois	United States	60611
4	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois	United States	60035
5	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
6	NorthShore Hematology Oncology-Libertyville	Libertyville	Illinois	United States	60048
7	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
8	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
9	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
10	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
11	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
12	Mayo Clinic	Rochester	Minnesota	United States	55905
13	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
14	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Douglas McNeel, ECOG-ACRIN Cancer Research Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01145508
• Other Study ID Numbers: NCI-2011-02048; NCI-2011-02048; CDR0000675173; E1809; E1809; E1809; U10CA180820; U10CA021115
• First Posted: Jun 16, 2010
• Last Update Posted: Sep 19, 2017
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Prostatic Neoplasms; Metronidazole; Prednisone; Cortisone; Docetaxel; Vaccines

Study Results

Participant Flow

Recruitment Details	Participants were recruited from Eastern Cooperative Oncology Group (ECOG) member institutions between December 29, 2010 and March 26, 2012.

Arm/Group Title	Arm A (Vaccine and Chemotherapy)	Arm B (Chemotherapy)
Arm/Group Description	Patients receive vaccinia-PSA(L155)-TRICOM vaccine subcutaneously (SC) on day 1 and fowlpox-PSA(L155)-TRICOM vaccine SC on days 15, 29, 43, and 57. Beginning on day 85, patients receive chemotherapy in a 21-day cycle. Docetaxel is administered intravenously (IV) over 1 hour on day 1. Prednisone is given orally (PO) twice daily on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. PSA-TRICOM vaccine: Given SC fowlpox-PSA-TRICOM vaccine: Given SC docetaxel: Given IV prednisone: Given PO	Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO twice daily on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV prednisone: Given PO
Period Title: Overall Study
STARTED	7	3
Treated	6	2
COMPLETED	2	1
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Arm A (Vaccine and Chemotherapy)	Arm B (Chemotherapy)	Total
Arm/Group Description	Patients receive vaccinia-PSA(L155)-TRICOM vaccine subcutaneously (SC) on day 1 and fowlpox-PSA(L155)-TRICOM vaccine SC on days 15, 29, 43, and 57. Beginning on day 85, patients receive chemotherapy in a 21-day cycle. Docetaxel is administered intravenously (IV) over 1 hour on day 1. Prednisone is given orally (PO) twice daily on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. PSA-TRICOM vaccine: Given SC fowlpox-PSA-TRICOM vaccine: Given SC docetaxel: Given IV prednisone: Given PO	Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO twice daily on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV prednisone: Given PO	Total of all reporting groups
Overall Participants	7	3	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	65	64
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	7 100%	3 100%	10 100%
Region of Enrollment (participants) [Number]
United States	7 100%	3 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from randomization to death or the date of last known alive.
Time Frame	Assessed every 3 months for 2 years, and then every 6 months for 3 years

Outcome Measure Data

Analysis Population Description

All randomized patients are included in the analysis.

Arm/Group Title	Arm A (Vaccine and Chemotherapy)	Arm B (Chemotherapy)
Arm/Group Description	Patients receive vaccinia-PSA(L155)-TRICOM vaccine subcutaneously (SC) on day 1 and fowlpox-PSA(L155)-TRICOM vaccine SC on days 15, 29, 43, and 57. Beginning on day 85, patients receive chemotherapy in a 21-day cycle. Docetaxel is administered intravenously (IV) over 1 hour on day 1. Prednisone is given orally (PO) twice daily on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. PSA-TRICOM vaccine: Given SC fowlpox-PSA-TRICOM vaccine: Given SC docetaxel: Given IV prednisone: Given PO	Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO twice daily on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV prednisone: Given PO
Measure Participants	7	3
Median (95% Confidence Interval) [Months]	20.8	NA

Adverse Events

Time Frame	Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
Arm/Group Title	Arm A (Vaccine and Chemotherapy)		Arm B (Chemotherapy)
Arm/Group Description	Patients receive vaccinia-PSA(L155)-TRICOM vaccine subcutaneously (SC) on day 1 and fowlpox-PSA(L155)-TRICOM vaccine SC on days 15, 29, 43, and 57. Beginning on day 85, patients receive chemotherapy in a 21-day cycle. Docetaxel is administered intravenously (IV) over 1 hour on day 1. Prednisone is given orally (PO) twice daily on days 1-21. Treatment with docetaxel and prednisone repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. PSA-TRICOM vaccine: Given SC fowlpox-PSA-TRICOM vaccine: Given SC docetaxel: Given IV prednisone: Given PO		Patients receive docetaxel IV over 1 hour on day 1 and prednisone PO twice daily on days 1-21. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV prednisone: Given PO
All Cause Mortality
	Arm A (Vaccine and Chemotherapy)		Arm B (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A (Vaccine and Chemotherapy)		Arm B (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		2/2 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	1/6 (16.7%)		1/2 (50%)
General disorders
Fatigue	1/6 (16.7%)		0/2 (0%)
Infections and infestations
Sepsis	1/6 (16.7%)		0/2 (0%)
Investigations
Lymphocyte count decreased	1/6 (16.7%)		0/2 (0%)
Neutrophil count decreased	4/6 (66.7%)		2/2 (100%)
White blood cell decreased	3/6 (50%)		1/2 (50%)
Metabolism and nutrition disorders
Dehydration	1/6 (16.7%)		0/2 (0%)
Nervous system disorders
Syncope	1/6 (16.7%)		0/2 (0%)
Vascular disorders
Thromboembolic event	1/6 (16.7%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Arm A (Vaccine and Chemotherapy)		Arm B (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		2/2 (100%)
Blood and lymphatic system disorders
Anemia	2/6 (33.3%)		1/2 (50%)
Eye disorders
Watering eyes	0/6 (0%)		1/2 (50%)
Gastrointestinal disorders
Bloating	0/6 (0%)		1/2 (50%)
Diarrhea	4/6 (66.7%)		1/2 (50%)
Dry mouth	2/6 (33.3%)		1/2 (50%)
Dyspepsia	2/6 (33.3%)		0/2 (0%)
Nausea	4/6 (66.7%)		0/2 (0%)
Vomiting	1/6 (16.7%)		0/2 (0%)
Gastrointestinal disorders - Other	0/6 (0%)		1/2 (50%)
General disorders
Chills	1/6 (16.7%)		0/2 (0%)
Edema face	1/6 (16.7%)		0/2 (0%)
Edema limbs	3/6 (50%)		1/2 (50%)
Fatigue	5/6 (83.3%)		2/2 (100%)
Fever	1/6 (16.7%)		0/2 (0%)
Injection site reaction	1/6 (16.7%)		1/2 (50%)
Infections and infestations
Nail infection	0/6 (0%)		1/2 (50%)
Paronychia	1/6 (16.7%)		0/2 (0%)
Skin infection	0/6 (0%)		1/2 (50%)
Injury, poisoning and procedural complications
Bruising	1/6 (16.7%)		0/2 (0%)
Investigations
Creatinine increased	0/6 (0%)		1/2 (50%)
Lymphocyte count decreased	2/6 (33.3%)		0/2 (0%)
Neutrophil count decreased	1/6 (16.7%)		0/2 (0%)
Platelet count decreased	0/6 (0%)		1/2 (50%)
White blood cell decreased	2/6 (33.3%)		1/2 (50%)
Metabolism and nutrition disorders
Anorexia	2/6 (33.3%)		0/2 (0%)
Dehydration	1/6 (16.7%)		1/2 (50%)
Hyperglycemia	0/6 (0%)		1/2 (50%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/6 (16.7%)		0/2 (0%)
Muscle weakness upper limb	0/6 (0%)		1/2 (50%)
Myalgia	2/6 (33.3%)		0/2 (0%)
Nervous system disorders
Dizziness	1/6 (16.7%)		1/2 (50%)
Dysgeusia	3/6 (50%)		2/2 (100%)
Headache	1/6 (16.7%)		0/2 (0%)
Peripheral sensory neuropathy	4/6 (66.7%)		1/2 (50%)
Psychiatric disorders
Insomnia	1/6 (16.7%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation	1/6 (16.7%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Alopecia	4/6 (66.7%)		2/2 (100%)
Dry skin	1/6 (16.7%)		0/2 (0%)
Hyperhidrosis	1/6 (16.7%)		0/2 (0%)
Nail discoloration	2/6 (33.3%)		0/2 (0%)
Nail loss	1/6 (16.7%)		0/2 (0%)
Nail ridging	1/6 (16.7%)		1/2 (50%)
Pruritus	1/6 (16.7%)		0/2 (0%)
Rash acneiform	0/6 (0%)		1/2 (50%)
Skin and subcutaneous tissue - Other	2/6 (33.3%)		1/2 (50%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.