Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Breast Diseases

Skin Diseases

odanacatib; 5mg oral, once daily for approximately 60 months.

Comparator: odanacatib

placebo; oral, once daily for approximately 60 months

Comparator: placebo

Medical Monitor

The purpose of this study is to test MK0822 on reducing the risk of bone metastasis in women with breast cancer.

A Study to Assess the Effects of MK0822 in Reducing the Risk of Bone Metastasis in Women With Breast Cancer (0822-029)

A Phase III Study to Assess the Safety, Tolerability, and Efficacy of MK0822 (Odanacatib) in Reducing the Risk of Bone Metastasis in Women With Breast Cancer

Merck Sharp & Dohme LLC

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Pleural Effusion

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Vorinostat

Tubulin Modulators

Antimitotic Agents

Histone Deacetylase Inhibitors

Enzyme Inhibitors

vorinostat; IV paclitaxel; IV carboplatin

vorinostat 400 mg capsules once daily. Up to 6 months of treatment

vorinostat

intravenous (IV) paclitaxel 200 mg/m2. Up to 6 months of treatment

Comparator: paclitaxel

intravenous (IV) carboplatin AUC 6mg/min/ml. Up to 6 months of treatment.

Comparator: carboplatin

vorinostat 400 mg placebo capsules once daily. Up to 6 months of treatment

This Phase III clinical trial which incorporates an initial Phase II component will determine the survival of advanced Non-small cell lung cancer patients when treated with MK0683 and paclitaxel plus carboplatin

A Clinical Trial of Vorinostat (MK0683, SAHA) in Combination With FDA Approved Cancer Drugs in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)(0683-056)

A Phase II/III Randomized, Double-Blind Study of Paclitaxel Plus Carboplatin in Combination With Vorinostat or Placebo in Patients With Stage IIIB (With Pleural Effusion) or Stage IV Non-Small-Cell Lung Cancer (NSCLC)

Defined as the time from date of randomization to death due to any cause. Patients without documented death at the time of the final analysis will be censored at the date of the last follow-up.

Defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in sum of the longest diameter of all target lesions, the appearance of a new lesion, or an increase in non-target lesions.

Response to treatment is defined as a complete response (CR) or partial response (PR) to treatment. Confirmation of response required a second assessment performed at least 4 weeks after the initial assessment. (PR is defined as at least a 30% reduction in sum of the longest diameter of all target lesions and no increase in non-target lesions).

The 5 untreated patients on study are not counted in the Adverse Events tables. Further, one patient was randomized to vorinostat but took placebo; and one patient, randomized to placebo, started vorinostat for 4 days before using placebo. Both patients are counted in the placebo group for Adverse Events, yielding 124 patients in each group.

Experimental arm: Vorinostat capsules (400 mg) once daily on Days -4 through 10 of Cycle 1 (25 day treatment cycle) and Days 1 through 14 of each subsequent 21 day treatment cycle; paclitaxel (200 mg/m2) and carboplatin (area under concentration/time curve of 6 mg/min/mL) administered by intravenous (IV) infusion on Day 1 of each treatment cycle.

Vorinostat + Paclitaxel + Carboplatin

Placebo Comparator arm: Placebo capsules once daily on Days -4 through 10 of Cycle 1 (25 day treatment cycle) and Days 1 through 14 of each subsequent 21 day treatment cycle; paclitaxel (200 mg/m2) and carboplatin (area under concentration/time curve of 6 mg/min/mL) administered by intravenous (IV) infusion on Day 1 of each treatment cycle.

Placebo + Paclitaxel + Carboplatin

Total

Less Than 65 years

65 years or Older

Age, Customized

Sex: Female, Male

White

Black

Asian

American Indian or Alaskan Native mix

Race/Ethnicity, Customized

IIIB

Cancer Stage

Eligible

Ineligible

Unknown

Eligibility to receive treatment with Bevacizumab

North America

Europe (United Kingdom, Italy, Germany, and Spain)

Asia

Rest of the World

Geographic region where the participant lived

The study was stopped following a pre-planned interim analysis because the goal for this study to continue was not met, based on 100 events, a reduction in the hazard ratio for progression-free survival by \> 23% with a one-sided p-value \< 0.1

Senior Vice President, Global Clinical Development

Intention-to-treat (ITT) population is defined as all randomized participants. Participants are counted in the group to which they are randomized.

Overall Survival

Full analysis set

(FAS) population defined as all randomized participants who have received at least one dose of study medication. There are 253 participants randomized in the study 5 didn't take any study medication. Therefore, 248 participants are included in this analysis population.

Progression Free Survival

Responder

Non-Responder

Full analysis set

(FAS) population is defined as all randomized participants who have received at least one dose of study medication. There are 253 participants randomized in the study. Five (5) didn't take any study medication. Therefore, 248 participants are included in this analysis population.

Number of Participants Who Had a Disease Response to Treatment

Overall Study

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Communicable Diseases

Virus Diseases

Papillomavirus Infections

Papilloma

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

DNA Virus Infections

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Disease Attributes

Vaccines

Participants received blinded qHPV vaccination at Day 1, Month 2, and Month 6 of the Base Study

Participants received blinded placebo at Day 1, Month 2, and Month 6 in the Base Study. They were eligible to receive open-label qHPV vaccine in Extension 1

qHPV intramuscular injection in three 0.5 mL doses over 6 months in the Base Study or EXT1

Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine

Placebo intramuscular injection in three 0.5 mL doses over 6 months.

Comparator: Placebo

This study was conducted to assess the safety, immunogenicity, efficacy and long-term effectiveness of a vaccine being evaluated for the prevention of human papillomavirus (HPV) infection and disease in mid-adult women.

The Base study vaccination period (V501-019) encompassed Day 1 through Month 7, during which time participants received randomly assigned, blinded Gardasil™ (V501, qHPV vaccine) or placebo at Day 1, Month 2 and Month 6. The Base study follow-up period continued through approximately Month 48.

The base study was extended in protocol V501-019-10 (EXT1). Participants who received placebo and participants who received only 1 dose of qHPV vaccine in the Base Study were offered a complete, open-label, 3-dose qHPV vaccine regimen (administered at EXT1 Day 1, Month 2 and Month 6). Participants who received only 2 doses of qHPV vaccine in the base study were offered a single additional dose of qHPV vaccine (administered at EXT1 Day 1). Participants were followed to EXT1 Month 7.

A Long Term Follow-Up (LTFU) extension study V501-019-21 (EXT2) was added to observe the long term safety, effectiveness, and immunogenicity of qHPV vaccine in approximately 1,600 women who participated in the Base Study at sites in Colombia. Data were collected over a period of 6-10 years following participant's enrollment in the original Base Study.

A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501, qHPV) in Mid-Adult Women (V501-019)

Safety, Immunogenicity, and Efficacy of Gardasil (V501 (Human Papilloma Virus [Types 6, 11, 16, 18] Recombinant Vaccine) in Mid-Adult Women - The FUTURE III (Females United to Unilaterally Reduce Endo/Ectocervical Cancer) Study

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

HPV 16/18: The two types of HPV (types 16/18) were determined by PCR testing

The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Day 1 to Year 4 conditional on having been event-free at Day 1.

The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 4 to Year 8 conditional on having been event-free from Day 1 to Year 4. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 6 to Year 10 conditional on having been event-free from Day 1 to Year 6.

The four HPV types were determined by PCR testing.

The four HPV types were determined by PCR testing. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

The four HPV types were determined by polymerase chain reaction (PCR) testing. VIN = vulvar intraepithelial neoplasia; VaIN = vaginal intraepithelial neoplasia; AIS = adenocarcinoma in situ.

An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or is an overdose. Vaccine-related SAEs are those deemed by the investigator to be definitely, probably, or possibly related to study vaccine.

An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or is an overdose.

The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Day 1 to Year 4, conditional on having been event-free at Day 1.

The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 4 to Year 8, conditional on having been event-free from Day 1 to Year 4. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 6 to Year 10, conditional on having been event-free from Day 1 to Year 6.

Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were \>20 for Type 6, \>16 for Type 11, \>20 for Type 16, and \>24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

HPV 6/11: The two types of HPV (types 6/11) were determined by PCR testing

This outcome measure was not analyzed because of diminished interest by experts in composite efficacy endpoints associated with these HPV types

Base Study: MedDRA v12.0; EXT1: MedDRA v14.1; LTFU (EXT2): MedDRA v18.1.

Adverse events are reported for all participants who received ≥1 dose of qHPV or placebo and had safety follow-up data.

Although other AEs were not solicited in EXT1 and LTFU (EXT2), some were voluntarily reported.

Participants received qHPV vaccination at Day 1, Month 2, and Month 6 and were followed up to approximately Month 48

qHPV Vaccine: Base Study

Participants received placebo at Day 1, Month 2, and Month 6 and were followed up to approximately Month 48

Placebo: Base Study

Participants who received placebo or an incomplete regimen of qHPV in the Base Study were offered open-label qHPV vaccine starting at approximately Month 60 (EXT1) and were followed up to Month 67

qHPV Vaccine: EXT1

Participants at sites in Colombia who received qHPV vaccination in the Base Study or in EXT1 were followed from Month 72 up to approximately Month 120 in LTFU (EXT2)

Long-term Follow-up: EXT2

Participants received qHPV vaccination at Day 1, Month 2, and Month 6 in the Base Study

qHPV Vaccine in Base Study

Participants received placebo at Day 1, Month 2, and Month 6 in the Base Study

Placebo in Base Study

Age, Continuous

Although the upper age limit for this study was 45 years old, one subject 46 years of age was randomized into the study.

Hispanic American

Native American

Multi-Racial

Polynesian

qHPV in Base Study

Participants who had no major protocol violations, received all 3 vaccinations, were seronegative to the relevant HPV type at Day 1 and PCR negative to the relevant HPV type Day 1 through Month 7, and provided follow-up data after Month 7

Incidence Rate of HPV 6/11/16/18 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer

Participants received placebo at Day 1, Month 2, and Month 6 and were followed to Month 48 in the Base Study

Participants who received \>=1 qHPV vaccination or placebo injection in the Base Study and had safety follow-up

Number of Participants With Vaccine- or Placebo-Related Serious Adverse Events (SAEs) in the Base Study

Participants who received placebo or an incomplete qHPV regimen in the Base Study and were offered open-label qHPV vaccine starting at approximately Month 60 in EXT1

Participants who received \>=1 qHPV vaccination in the Base Study or EXT1 and had safety follow-up

Number of Participants With Vaccine-Related SAEs After Vaccine Administration

qHPV in Base Study: All Participants

Base Study: Placebo

Number of Participants With an SAE Resulting in Death After Vaccine Administration

Participants who had no major protocol violations, received all 3 vaccinations, were seronegative to the HPV types at Day 1 and PCR negative to the HPV types through Month 7, and provided follow-up data.

Cumulative Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN) or Condyloma: Day 1 to Year 4

Participants who had no major protocol violations, received all 3 vaccinations, were seronegative to the HPV types at Day 1 and PCR negative to the HPV types through Month 7, and provided follow-up data after Year 4. This Outcome Measure applied only to participants who received qHPV in the Base Study.

Cumulative Incidence of HPV 6/11/16/18-related CIN or Condyloma: Year 4 to 8

Participants who had no major protocol violations, received all 3 vaccinations, were seronegative to the HPV types at Day 1 and PCR negative to the HPV types through Month 7, and provided follow-up data after Year 6. This Outcome Measure applied only to participants who received qHPV in the Base Study.

Cumulative Incidence of HPV 6/11/16/18-related CIN or Condyloma: Year 6 to 10

Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Day 1 to Year 4

Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Year 4 to 8

Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Year 6 to 10

HPV Type 6: n=1249, 605, 644

HPV Type 11: n=1249, 605, 644

HPV Type 16: n=1269, 612, 657

HPV Type 18: n=1430, 708, 722

24 to 34 year-old participants received qHPV vaccination at Day 1, Month 2, and Month 6 in the Base Study

qHPV in Base Study: Participants 24 to 34 Years Old

35 to 45 year-old participants received qHPV vaccination at Day 1, Month 2, and Month 6 in the Base Study

qHPV in Base Study: Participants 35 to 45 Years Old

Participants who received ≥1 qHPV vaccination. n = participants who were seronegative to the HPV type on Day 1 and PCR negative to the HPV type through Month 7, received 3 doses of qHPV, had a valid postdose 3 serology result for the HPV type, and did not fail any exclusion criteria pertinent to immunogenicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Assess the Effects of MK0822 in Reducing the Risk of Bone Metastasis in Women With Breast Cancer (0822-029)	NCT00692458	Breast Cancer	Comparator: oda... Comparator: pla...	18 Years -	Merck Sharp & Dohme LLC
A Clinical Trial of Vorinostat (MK0683, SAHA) in Combination With FDA Approved Cancer Drugs in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)(0683-056)	NCT00473889	Stage IIIB or I...	vorinostat Comparator: pac... Comparator: car... Comparator: pla...	18 Years -	Merck Sharp & Dohme LLC
A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501, qHPV) in Mid-Adult Women (V501-019)	NCT00090220	Healthy Adult F... Prevention Papillomavirus ... Human Papilloma...	Quadrivalent Hu... Comparator: Pla...	24 Years - 45 Years	Merck Sharp & Dohme LLC
Bicalutamide and Ridaforolimus in Men With Prostate Cancer (MK-8669-002)	NCT00777959	Prostate Cancer	ridaforolimus (... Comparator: Pla... open-label rida...	18 Years -	Merck Sharp & Dohme LLC
An Immunogenicity and Safety Study of Gardasil® in Chinese Subjects (V501-030)(COMPLETED)	NCT00496626	Papillomavirus ...	Quadrivalent Hu... Comparator: Pla...	9 Years - 45 Years	Merck Sharp & Dohme LLC
An Immunogenicity and Safety Study of Gardasil® in Chinese Subjects (V501-030)(COMPLETED)	NCT00496626	Papillomavirus ...	Quadrivalent Hu... Comparator: Pla...	9 Years - 45 Years	Merck Sharp & Dohme LLC
Bicalutamide and Ridaforolimus in Men With Prostate Cancer (MK-8669-002)	NCT00777959	Prostate Cancer	ridaforolimus (... Comparator: Pla... open-label rida...	18 Years -	Merck Sharp & Dohme LLC
A Study to Assess the Effects of MK0822 in Reducing the Risk of Bone Metastasis in Women With Breast Cancer (0822-029)	NCT00692458	Breast Cancer	Comparator: oda... Comparator: pla...	18 Years -	Merck Sharp & Dohme LLC
A Study of Gardasil (V501) in Preadolescents and Adolescents (V501-018)	NCT00092547	Human Papillomavirus ...	V501 Comparator: Pla...	9 Years - 15 Years	Merck Sharp & Dohme LLC
A Clinical Trial of Vorinostat (MK0683, SAHA) in Combination With FDA Approved Cancer Drugs in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)(0683-056)	NCT00473889	Stage IIIB or I...	vorinostat Comparator: pac... Comparator: car... Comparator: pla...	18 Years -	Merck Sharp & Dohme LLC

Spots Global Cancer Trial Database for comparator: placebo