Belinostat, Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Cancer of Unknown Primary

• Sponsor: Onxeo (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00873119
• Collaborator: Spectrum Pharmaceuticals, Inc (Industry)
• Enrollment: 89
• Locations: 23
• Arms: 2
• Duration (Months): 46
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess efficacy and safety of belinostat in combination with carboplatin and paclitaxel in patients with previously untreated carcinoma of unknown primary.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma of Unknown Primary	Drug: belinostat, carboplatin, paclitaxel; Drug: carboplatin, paclitaxel	Phase 2

Detailed Description

This is an open-label, multinational, multicenter, randomized, comparative efficacy and safety study in previously untreated patients with carcinoma of unknown primary. Patients meeting inclusion and exclusion criteria will be randomized to treatment in Arm A (BelCaP) or Arm B (CaP).

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Randomized Phase II Trial of Belinostat (PXD101) in Combination With Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Previously Untreated Carcinoma of Unknown Primary
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A - BelCaP Group A: belinostat 1000 mg/m² administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat 2000 mg administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel 175 mg/m² administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Drug: belinostat, carboplatin, paclitaxel; Other Names: PXD101, Belinostat Carboplatin Paclitaxel, Taxol
Active Comparator: Arm B - CaP Group B: paclitaxel 175 mg/m² administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.	Drug: carboplatin, paclitaxel; Other Names: Carboplatin Paclitaxel, Taxol

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study]

   Time from the date of randomization to the time of disease progression or death due to any cause, measured by RECIST criteria (Response Evaluation Criteria In Solid Tumors).

Secondary Outcome Measures

1. Best Overall Response [Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study]

   The best overall response in an individual patient according to the RECIST criteria (Eisenhauer 2009 ) is the best response recorded from the start of the treatment until disease progression/recurrence. Objective response is defined as best overall response of complete response (CR) or partial response (PR)

2. Overall Survival (OS) [Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study]

   Time from the date of randomization to the date of death

3. Time to Response [Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study]

   For patients with overall best response being CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status is recorded first) were met

4. Duration of Response [Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study]

   Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date that PD ([Progressive Disease]) or death was documented

5. Time to Progression (TTP) [Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study]

   Time from the date of randomization to the time of disease progression

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with CUP where the primary site had not been revealed by complete history, physical examination (including gynecological examination when appropriate), computed tomography (CT) scan of the chest, abdomen and pelvis, bilateral mammography (in women with adenocarcinoma or poorly differentiated carcinoma), routine laboratory studies (complete blood cell counts, electrolytes, urinalysis, liver and renal function tests), and directed work-up of any other symptomatic areas.

• Light microscopic pathologic diagnosis of adenocarcinoma (including poorly differentiated), squamous cell carcinoma, or poorly differentiated carcinoma. Patients with poorly differentiated carcinoma must have immunohistochemical stains to confirm the diagnosis of carcinoma, and to rule out other tumor types. Note: patients with a light microscopic histology diagnosis of "poorly differentiated neoplasm, not otherwise classified" did not fulfill the criteria for inclusion, unless immunohistochemical staining confirmed the diagnosis of carcinoma.

• Signed consent of an IRB ([Institutional Review Board])/IEC ([Independent ethics committee]) approved ICF ([Informed Consent Form]).

• At least one measurable lesion according to RECIST ([response evaluation criteria in solid tumors ]) criteria. Note, target lesions could only be selected within previously irradiated areas if newly arising or clearly progressing after irradiation as proven by repeat scanning

• Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2.

• Age ≥ 18 years.

• A negative serum or urine pregnancy test for women of childbearing potential. Postmenopausal women must have been amenorrheic for ≥ 12 months to be considered of non-childbearing potential.

• Serum potassium within normal range.

• Acceptable coagulation status: Prothrombin time/International normalized ratio PT/INR ([international normalized ratio]), and activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN) or in the therapeutic range if on anticoagulation therapy.

• Acceptable liver, renal and bone marrow function including the following:

1. Bilirubin ≤ 1.5 times ULN (if liver metastases were present, then ≤ 3 × ULN was allowed).

2. Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine amino transferase/serum glutamic pyruvic transaminase (ALT/SGPT), and alkaline phosphatase ≤ 3 times ULN (if liver metastases were present, then ≤ 5 × ULN was allowed).

3. An estimated creatinine clearance ≥ 45 mL/min using an appropriate formula (Appendix C, protocol version 1.0, Appendix 16.1.1), or measured ethylenediaminetetraacetic acid (EDTA) renal clearance ≥ 45 mL/min.

4. Absolute neutrophils count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L.

5. Hemoglobin ≥ 9.0 g/dL or ≥ 5.6 mmol/L (patients with chronic anemia due to underlying disease and its treatment could undergo blood transfusion prior to treatment in order to meet this criteria).

Exclusion Criteria:

• Patients with well recognized subsets of CUP site where treatments directed towards a defined tumor type, or surgery, alternatively radiotherapy, can be advised:

• Women with adenocarcinoma involving only axillary lymph nodes.

• Women with papillary serous carcinoma of the peritoneum.

• Women with adenocarcinoma with positive staining for estrogen receptor (ER) or progesterone receptor.

• Young men (< 45 years) with poorly differentiated carcinoma consistent with an extragonadal germ cell tumor (carcinoma involving mediastinum or retroperitoneum, or elevated levels of beta-human chorionic gonadotropin or alpha-fetoprotein).

• Men with bone metastases and/or adenocarcinoma, and abnormally elevated PSA ([Prostate specific antigen]) in their plasma.

• Patients with squamous cell carcinoma involving only cervical lymph nodes, or inguinal lymph nodes.

• Patients with neuroendocrine carcinomas determined according to standard pathology diagnosis procedures, including stains.

• Patients with potentially completely resectable metastatic disease, or disease which can be adequately treated with radiotherapy only.

• Patients with brain or meningeal metastases. Note, patients with adequately treated brain metastases, e.g. surgically resected, or adequately controlled by radiotherapy, with no residual neurological symptoms due to metastases and no steroid treatment required, could be enrolled. If clinical suspicion, adequate investigations should be performed to rule out brain metastases or meningeal involvement.

• Prior systemic anti-tumor therapy, including chemotherapy administered in association to radiotherapy for sensitization, for CUP. Note, prior radiotherapy or surgery was allowed provided treatment was completed at least 4 weeks before randomization.

• Treatment with investigational agents, including non-anti-tumor agents, within the last 4 weeks before randomization.

• Co-existing active severe infection or any co-existing medical condition assessed by the Investigator as likely to interfere with study procedures.

• Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medication to control heart rate in patients with atrial fibrillation was allowed, if on stable medication for at least the last month prior to randomization and the medication not listed as causing Torsade de Points (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1), or evidence of acute ischemia on ECG.

• Marked baseline prolongation of QT/QTc ([corrected QT interval]) interval, i.e., demonstration of a QTc interval > 450 millisecond (ms); Long QT Syndrome; the required use of concomitant medication that may cause Torsade de Pointes (Section 13.2, Appendix B, protocol version 1.0, Appendix 16.1.1).

• Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.

• History of a previous malignancy within 5 years with the exception of non-metastatic non-melanoma skin cancer or cervical carcinoma in situ. Prior systemic therapy for other malignancy completed at least 5 years before randomization is allowed.

Implemented with amendment 2 (study centers in France only): History of a previous malignancy, irrespective of time since diagnosis/treatment, with the exception of non metastatic non-melanoma skin cancer or cervical carcinoma in situ.

• Known hypersensitivity to either platinum compounds or paclitaxel, or any components of the study medications, and inability for desensitization.

• Known infection with HIV, or known active Hepatitis B or C infection.

• Peripheral neuropathy ≥ Grade 2.

• Pregnant or lactating females.

• Women of childbearing age and potential who are not willing to use effective contraception during the study and until 30 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study and until 30 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra uterine devices, sexual abstinence or vasectomized partner.

• Patients that are not affiliated with social security (study centers in France only).

• Implemented with amendment 1 (study centers in Denmark only): Hearing impairment assessed by the Investigator as being of such a degree that treatment with carboplatin cannot be initiated.

• Implemented with amendment 1 (study centers in Denmark only): Bleeding tumors.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists	Fort Myers	Florida	United States	33619
2	Northwest Georgia Oncology Centers	Marietta	Georgia	United States	30060
3	Baton Rouge Medical Center	Baton Rouge	Louisiana	United States	70809
4	Center for Cancers and Blood Disorders	Bethesda	Maryland	United States	20817
5	Research Medical Center	Kansas City	Missouri	United States	64132
6	Oncology Hematology Care Inc.	Cincinnati	Ohio	United States	45242
7	South Carolina Oncology Associates	Columbia	South Carolina	United States	29210
8	Chattanooga Oncology & Hematology Associates, PC	Chattanooga	Tennessee	United States	37404
9	Tennessee Oncology Sarah Cannon Research	Nashville	Tennessee	United States	37203
10	South Texas Oncology and Hematology	San Antonio	Texas	United States	78258
11	Virginia Cancer Institute	Richmond	Virginia	United States	23230
12	H:S Rigshospital, The Finsen Centre	Copenhagen		Denmark	DK-2100
13	CRLCC Francois Baclesse, Oncologie medicale	Caen		France	14000
14	Centre Oscar Lambert	Lille		France	59020
15	Centre Léon Bérard, Oncologie	Lyon		France	69008
16	Centre Eugène Marquis	Rennes cedex		France	35042
17	Centre Henri Becquerel, Oncologie Médicale	Rouen		France	76038
18	Institut de Cancerologie de la Loire	Saint Priest en Jarez		France	42270
19	Institut Gustave Roussy IGR	Villejuif cedex		France	94805
20	Carl-Gustav-Carus Medicinische Klinik und Poliklinik I	Dresden		Germany	01307
21	Kliniken Essen-Mitte	Essen		Germany	45136
22	ASKLEPIOS Klinik Altona	Hamburg		Germany	22763
23	Ostholstein-Onkologie	Oldenburg in Holstein		Germany	23758

Sponsors and Collaborators

• Onxeo
• Spectrum Pharmaceuticals, Inc

Investigators

• Study Director: e-mail contact via [e-mail], Onxeo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Onxeo
• ClinicalTrials.gov Identifier: NCT00873119
• Other Study ID Numbers: PXD101-CLN-17
• First Posted: Apr 1, 2009
• Last Update Posted: Jul 28, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Onxeo: Belinostat; PXD101; Carboplatin; Paclitaxel; CUP; Carcinoma of unknown primary; Occult primary
• Additional relevant MeSH terms: Carcinoma; Neoplasms, Unknown Primary; Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Belinostat

Study Results

Participant Flow

Arm/Group Title	Arm A - BelCaP	Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Period Title: Overall Study
STARTED	44	45
COMPLETED	0	19
NOT COMPLETED	44	26

Baseline Characteristics

Arm/Group Title	Arm A - BelCaP	Arm B - CaP	Total
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.	Total of all reporting groups
Overall Participants	44	45	89
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 65.9%	31 68.9%	60 67.4%
>=65 years	15 34.1%	14 31.1%	29 32.6%
Sex: Female, Male (Count of Participants)
Female	24 54.5%	23 51.1%	47 52.8%
Male	20 45.5%	22 48.9%	42 47.2%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	Time from the date of randomization to the time of disease progression or death due to any cause, measured by RECIST criteria (Response Evaluation Criteria In Solid Tumors).
Time Frame	Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All patients randomized to one of the two treatment groups were included in the ITT population, 12 patients (5 in Arm A and 7 in Arm B) were censored due to lack of efficacy

Arm/Group Title	Arm A - BelCaP	Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Measure Participants	39	38
Median (95% Confidence Interval) [months]	5.4	5.3

2. Secondary Outcome

Title	Best Overall Response
Description	The best overall response in an individual patient according to the RECIST criteria (Eisenhauer 2009 ) is the best response recorded from the start of the treatment until disease progression/recurrence. Objective response is defined as best overall response of complete response (CR) or partial response (PR)
Time Frame	Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All patients randomized to one of the two treatment groups were included in the ITT population.

Arm/Group Title	Arm A - BelCaP	Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Measure Participants	42	44
Number [percentage of participants]	43.2 98.2%	22.2 49.3%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Time from the date of randomization to the date of death
Time Frame	Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All patients randomized to one of the two treatment groups were included in the ITT population. 18 patients (10 in Arm A and 8 in Arm B) were censored.

Arm/Group Title	Arm A - BelCaP	Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Measure Participants	34	37
Median (95% Confidence Interval) [months]	11.5	9.1

4. Secondary Outcome

Title	Time to Response
Description	For patients with overall best response being CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status is recorded first) were met
Time Frame	Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Outcome Measure Data

Analysis Population Description

Patients with overall best response being either complete response or partial response.

Arm/Group Title	Arm A - BelCaP	Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Measure Participants	19	10
Median (Full Range) [months]	3.2	NA

5. Secondary Outcome

Title	Duration of Response
Description	Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date that PD ([Progressive Disease]) or death was documented
Time Frame	Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All patients randomized to one of the two treatment groups were included in the ITT population. Three patients, 2 in Arm A and 1 in Arm B, were not treated with study medication

Arm/Group Title	Arm A - BelCaP	Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Measure Participants	19	10
Median (95% Confidence Interval) [months]	4.6	6.5

6. Secondary Outcome

Title	Time to Progression (TTP)
Description	Time from the date of randomization to the time of disease progression
Time Frame	Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: All patients randomized to one of the two treatment groups were included in the ITT population. 26 patients (12 in Arm A and 14 in Arm B) were censored. One patient in each arm had no information reported.

Arm/Group Title	Arm A - BelCaP	Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.	Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
Measure Participants	31	30
Median (95% Confidence Interval) [months]	5.7	5.6

Adverse Events

Adverse Event Reporting Description	Safety population consist of 86 of 89 included patients. 3 patients (2 in Arm A and 1 in Arm B) did not receive study medication
Arm/Group Title	Arm A - BelCaP		Arm B - CaP
Arm/Group Description	Group A: belinostat (1000 mg/m²) administered as a 30 minute IV infusion once daily on days 1, 2 and 3, with at least 18 hours between infusions, followed by belinostat (2000 mg) administered orally once daily on days 4 and 5, every 3-weeks, in combination with paclitaxel (175 mg/m²) administered as an IV infusion following the infusion of belinostat on cycle day 3, and carboplatin (AUC 6) administered as a 30-60 minute IV infusion directly after the paclitaxel administration on cycle day 3.		Group B: paclitaxel (175 mg/m²) administered as an IV infusion directly followed by carboplatin (AUC 6) administered as a 30-60 minute IV infusion on cycle day 1 of a 3-weekly cycle.
All Cause Mortality
	Arm A - BelCaP		Arm B - CaP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A - BelCaP		Arm B - CaP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/42 (52.4%)		10/44 (22.7%)
Blood and lymphatic system disorders
Febrile bone marrow aplasia	1/42 (2.4%)		0/44 (0%)
Anaemia	0/42 (0%)		1/44 (2.3%)
Febrile neutropenia	0/42 (0%)		1/44 (2.3%)
Cardiac disorders
Cardiac arrest	1/42 (2.4%)		0/44 (0%)
Eye disorders
Visual impairment	1/42 (2.4%)		0/44 (0%)
Gastrointestinal disorders
Vomiting	4/42 (9.5%)		0/44 (0%)
Abdominal pain	1/42 (2.4%)		1/44 (2.3%)
Nausea	1/42 (2.4%)		0/44 (0%)
Immune system disorders
Drug hypersensitivity	2/42 (4.8%)		2/44 (4.5%)
Hypersensitivity	1/42 (2.4%)		1/44 (2.3%)
Infections and infestations
Cystitis	1/42 (2.4%)		0/44 (0%)
Device related infection	1/42 (2.4%)		0/44 (0%)
Retroperitoneal abscess	1/42 (2.4%)		0/44 (0%)
Urinary tract infection	1/42 (2.4%)		0/44 (0%)
Upper respiratory tract infection	0/42 (0%)		1/44 (2.3%)
Cellulitis	0/42 (0%)		1/44 (2.3%)
Neutropenic infection	0/42 (0%)		1/44 (2.3%)
Pneunomia	0/42 (0%)		1/44 (2.3%)
Injury, poisoning and procedural complications
Femur fracture	1/42 (2.4%)		0/44 (0%)
Hip fracture	1/42 (2.4%)		0/44 (0%)
Infusion related reaction	1/42 (2.4%)		0/44 (0%)
Investigations
Haemoglobin decreased	1/42 (2.4%)		0/44 (0%)
Transaminases increased	1/42 (2.4%)		0/44 (0%)
Metabolism and nutrition disorders
Dehydration	2/42 (4.8%)		0/44 (0%)
Decreased appetite	1/42 (2.4%)		0/44 (0%)
Hypomagnesaemia	0/42 (0%)		1/44 (2.3%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/42 (2.4%)		0/44 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	1/42 (2.4%)		0/44 (0%)
Metastatic neoplasm	1/42 (2.4%)		0/44 (0%)
Psychiatric disorders
Panic attack	1/42 (2.4%)		0/44 (0%)
Mental status changes	0/42 (0%)		1/44 (2.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	3/42 (7.1%)		0/44 (0%)
Acute respiratory failure	1/42 (2.4%)		0/44 (0%)
Dyspnoea	1/42 (2.4%)		0/44 (0%)
Aspiration	0/42 (0%)		1/44 (2.3%)
Vascular disorders
Arterial occlusive disease	1/42 (2.4%)		0/44 (0%)
Deep vein thrombosis	1/42 (2.4%)		0/44 (0%)
Venous stenosis	1/42 (2.4%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	Arm A - BelCaP		Arm B - CaP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/42 (100%)		43/44 (97.7%)
Blood and lymphatic system disorders
Anaemia	17/42 (40.5%)		7/44 (15.9%)
Thrombocytopenia	13/42 (31%)		10/44 (22.7%)
Neutropenia	14/42 (33.3%)		8/44 (18.2%)
Leukopenia	5/42 (11.9%)		4/44 (9.1%)
Ear and labyrinth disorders
Tinnitus	0/42 (0%)		3/44 (6.8%)
Gastrointestinal disorders
Nausea	36/42 (85.7%)		26/44 (59.1%)
Diarrhoea	24/42 (57.1%)		17/44 (38.6%)
Vomiting	26/42 (61.9%)		13/44 (29.5%)
Constipation	19/42 (45.2%)		18/44 (40.9%)
Abdominal pain	8/42 (19%)		11/44 (25%)
Dry mouth	6/42 (14.3%)		1/44 (2.3%)
Abdominal pain upper	4/42 (9.5%)		2/44 (4.5%)
Abdominal distension	3/42 (7.1%)		2/44 (4.5%)
Stomatitis	1/42 (2.4%)		3/44 (6.8%)
General disorders
Fatigue	27/42 (64.3%)		29/44 (65.9%)
Oedema peripheral	10/42 (23.8%)		10/44 (22.7%)
Asthenia	6/42 (14.3%)		5/44 (11.4%)
Pyrexia	7/42 (16.7%)		4/44 (9.1%)
Chest pain	5/42 (11.9%)		2/44 (4.5%)
Mucosal inflammation	5/42 (11.9%)		2/44 (4.5%)
Chills	3/42 (7.1%)		2/44 (4.5%)
Pain	2/42 (4.8%)		3/44 (6.8%)
Immune system disorders
Drug hypersensitivity	6/42 (14.3%)		5/44 (11.4%)
Infections and infestations
Urinary tract infection	4/42 (9.5%)		3/44 (6.8%)
Nasopharyngitis	1/42 (2.4%)		5/44 (11.4%)
Oral candidiasis	3/42 (7.1%)		1/44 (2.3%)
Investigations
Weight decreased	4/42 (9.5%)		5/44 (11.4%)
Platelet count decreased	3/42 (7.1%)		4/44 (9.1%)
Haemoglobin decreased	3/42 (7.1%)		2/44 (4.5%)
Increased haemoglobin	0/42 (0%)		3/44 (6.8%)
Neutrophil count decreased	3/42 (7.1%)		0/44 (0%)
Metabolism and nutrition disorders
Decreased appetite	20/42 (47.6%)		16/44 (36.4%)
Dehydration	10/42 (23.8%)		2/44 (4.5%)
Hypomagnesaemia	1/42 (2.4%)		8/44 (18.2%)
Hyperglycaemia	3/42 (7.1%)		4/44 (9.1%)
Hypoalbuminaemia	0/42 (0%)		3/44 (6.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/42 (16.7%)		14/44 (31.8%)
Back pain	9/42 (21.4%)		10/44 (22.7%)
Myalgia	5/42 (11.9%)		14/44 (31.8%)
Pain in extremity	11/42 (26.2%)		6/44 (13.6%)
Musculoskeletal pain	6/42 (14.3%)		3/44 (6.8%)
Bone pain	3/42 (7.1%)		5/44 (11.4%)
Muscle spasms	2/42 (4.8%)		5/44 (11.4%)
Muscular weakness	1/42 (2.4%)		5/44 (11.4%)
Nervous system disorders
Neuropathy peripheral	15/42 (35.7%)		8/44 (18.2%)
Peripheral sensory neuropathy	7/42 (16.7%)		11/44 (25%)
Dizziness	6/42 (14.3%)		7/44 (15.9%)
Dysgeusia	6/42 (14.3%)		5/44 (11.4%)
Headache	5/42 (11.9%)		6/44 (13.6%)
Paraesthesia	6/42 (14.3%)		2/44 (4.5%)
Psychiatric disorders
Insomnia	7/42 (16.7%)		9/44 (20.5%)
Anxiety	6/42 (14.3%)		3/44 (6.8%)
Renal and urinary disorders
Dysuria	3/42 (7.1%)		3/44 (6.8%)
Respiratory, thoracic and mediastinal disorders
Cough	10/42 (23.8%)		9/44 (20.5%)
Dyspnoea	9/42 (21.4%)		10/44 (22.7%)
Epistaxis	5/42 (11.9%)		4/44 (9.1%)
Productive cough	1/42 (2.4%)		4/44 (9.1%)
Pulmonary embolism	4/42 (9.5%)		1/44 (2.3%)
Hiccups	3/42 (7.1%)		0/44 (0%)
Skin and subcutaneous tissue disorders
Alopecia	22/42 (52.4%)		27/44 (61.4%)
Rash	10/42 (23.8%)		4/44 (9.1%)
Pruritus	3/42 (7.1%)		6/44 (13.6%)
Dry skin	4/42 (9.5%)		3/44 (6.8%)
Night sweats	0/42 (0%)		3/44 (6.8%)
Vascular disorders
Flushing	6/42 (14.3%)		7/44 (15.9%)
Hypotension	5/42 (11.9%)		2/44 (4.5%)
Phlebitis	3/42 (7.1%)		1/44 (2.3%)
Hot flush	0/42 (0%)		3/44 (6.8%)

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.