Safety and Efficacy Study of Pembrolizumab (MK-3475) Combined With Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Advance Melanoma (MK-7902-003/E7080-G000-312/LEAP-003)

Malignant Melanoma Clinical Trial

Official title:

A Phase 3 Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) and Lenvatinib (E7080/MK-7902) Versus Pembrolizumab Alone as First-line Intervention in Participants With Advanced Melanoma (LEAP-003)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03820986
• Other study ID #: 7902-003
• Secondary ID: MK-7902-003E7080
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 12, 2019
• Est. completion date: November 8, 2024

Study information

• Verified date: February 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) as first-line treatment in adults with no prior systemic therapy for their advanced melanoma.

The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo as assessed by Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Description:

As of 03-April-2023 active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 674
• Est. completion date: November 8, 2024
• Est. primary completion date: January 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically or cytologically confirmed melanoma.

• Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer guidelines, not amenable to local therapy.

• Has been untreated for advanced or metastatic disease except as follows:

1. Proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease. Participants that do not have a BRAF V600 mutation but did receive BRAF or BRAF/MEKi therapy are eligible to participate in this study after discussion with the medical monitor.

2. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [anti-PD-1] therapy or interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation.

• Have documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during the Screening period (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).

• Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

• Has the presence of =1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.

• Provides a tumor biopsy. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized. The tumor biopsy may not be obtained from a lone target lesion. Confirmation of presence of tumor tissue is not required prior to randomization.

• Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the intervention.

• Male participants must agree to use contraception during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period. Please note that 7 days after lenvatinib/placebo is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed. Contraception use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.

• Female participants must not be pregnant, not breastfeeding, and =1 of the following conditions applies:

1. Not a woman of childbearing potential (WOCBP). OR

2. A WOCBP who agrees to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment.

• The participant (or legally acceptable representative) has provided documented informed consent for the study.

• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.

• Has adequate organ function.

Exclusion Criteria:

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.

• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.

• Has known active central nervous system metastases and/or carcinomatous meningitis.

• Has ocular melanoma.

• Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody.

• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

• Has an active infection requiring systemic therapy.

• Has known history of human immunodeficiency virus (HIV) infection

• Has known history of or is positive for hepatitis B virus or hepatitis C virus infection.

• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

• Has a history of active tuberculosis (Bacillus tuberculosis).

• Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.

• Has had a major surgery within 3 weeks prior to first dose of study intervention. Note: Adequate wound healing after major surgery must be assessed clinically independent of time elapsed for eligibility.

• Has a preexisting Grade =3 gastrointestinal or non-gastrointestinal fistula.

• Has radiographic evidence of encasement or invasion of major blood vessel, or of intratumoral cavitation.

• Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study treatment.

• Has clinically significant cardiovascular disease from 12 months of the first dose of study treatment including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.

• Has urine protein =1 g/24-hour. Note: Participants with =2+ (=100 mg/dL) proteinuria on urine dipstick testing (or urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.

• Prolongation of QTcF interval to >480 ms. Note: If the QTcF is prolonged to >480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility.

• Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram.

• Has received prior therapy in the adjuvant setting. Note: Targeted therapy, anti-CTLA-4, or anti-PD-1 may be allowed.

• Has received prior systemic treatment for unresectable or metastatic melanoma other than targeted therapy as noted in Inclusion Criteria above

• Has received prior therapy with a monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study treatment or not recovered (=Grade 1 or at Baseline) from adverse events due to previously administered agents.

Exception to this rule would be use of denosumab, which is not excluded. Note: Participants with alopecia and =Grade 2 neuropathy are an exception and may enroll.

• Has received prior radiotherapy within 2 weeks of first dose of study treatment (Cycle 1 Day 1). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.

• Has received live vaccine within 30 days before the first dose of study treatment.

• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

• Has had an allogeneic tissue/solid organ transplant.

• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Lenvatinib
Oral capsule
• Placebo for lenvatinib
Oral capsule

Locations

Country	Name	City	State
Australia	Eastern Health ( Site 0457)	Box Hill	Victoria
Australia	Lismore Base Hospital ( Site 0453)	Lismore	Australian Capital Territory
Australia	Fiona Stanley Hospital ( Site 0456)	Murdoch	Western Australia
Australia	Melanoma Institute Australia ( Site 0452)	North Sydney	New South Wales
Australia	Westmead Hospital ( Site 0451)	Westmead	New South Wales
Australia	Princess Alexandra Hospital ( Site 0454)	Wooloongabba	Queensland
Austria	LKH Universitatsklinikum Graz ( Site 0776)	Graz	Steiermark
Austria	Medizinische Universitat Wien ( Site 0778)	Wien
Brazil	PERSONAL - Oncologia de Precisao e Personalizada ( Site 0399)	Belo Horizonte	Minas Gerais
Brazil	Hospital de Caridade de Ijui ( Site 0391)	Ijui	Rio Grande Do Sul
Brazil	Hospital Sao Vicente de Paulo ( Site 0396)	Passo Fundo	Rio Grande Do Sul
Brazil	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0397)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional de Cancer Hospital do Cancer II ( Site 0394)	Rio de Janeiro
Canada	BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0661)	Kelowna	British Columbia
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)	Montreal	Quebec
Canada	McGill University Health Centre ( Site 0651)	Montreal	Quebec
Canada	Lions Gate Hospital ( Site 0662)	North Vancouver	British Columbia
Canada	Sunnybrook Research Institute ( Site 0654)	Toronto	Ontario
Chile	Fundacion Arturo Lopez Perez FALP ( Site 0421)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile ( Site 0422)	Santiago	Region M. De Santiago
Chile	Sociedad Medica Aren y Bachero Limitada ( Site 0426)	Santiago	Region M. De Santiago
Chile	Centro Investigación del Cáncer James Lind ( Site 0425)	Temuco	Araucania
Chile	Oncocentro ( Site 0424)	Vina del Mar	Valparaiso
China	Beijing Cancer Hospital ( Site 0601)	Beijing	Beijing
China	The First Hospital Of Jilin University ( Site 0603)	Chang Chun	Jilin
China	Fujian Provincial Cancer Hospital ( Site 0612)	Fuzhou	Fujian
China	Sun Yat-Sen University Cancer Center ( Site 0602)	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital ( Site 0605)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0608)	Hangzhou	Zhejiang
China	Yunnan Cancer Hospital ( Site 0604)	Kunming	Yunnan
China	Nanjing Drum Tower Hospital ( Site 0609)	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center ( Site 0607)	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital ( Site 0606)	Tianjin	Tianjin
China	Henan Cancer Hospital ( Site 0610)	Zhengzhou	Henan
France	Centre Hospitalier Victor Dupouy ( Site 0012)	Argenteuil	Val-d Oise
France	Hopital Ambroise Pare Boulogne ( Site 0007)	Boulogne-Billancourt	Hauts-de-Seine
France	CHU Dijon Bourgogne ( Site 0010)	Dijon	Cote-d Or
France	CHRU Lille - Hopital Claude Huriez ( Site 0004)	Lille	Nord
France	Hopital La Timone ( Site 0002)	Marseille	Bouches-du-Rhone
France	Hopital ARCHET 2 ( Site 0009)	Nice	Alpes-Maritimes
France	CHU de la Miletrie Poitiers ( Site 0011)	Poitiers	Vienne
France	CHU de Rouen ( Site 0013)	Rouen	Seine-Maritime
France	Institut Claudius Regaud IUCT Oncopole ( Site 0003)	Toulouse	Haute-Garonne
France	Institut Gustave Roussy ( Site 0001)	Villejuif	Val-de-Marne
Germany	Hautkrebszentrum Buxtehude ( Site 0037)	Buxtehude	Niedersachsen
Germany	Universitaetsklinikum Carl Gustav Carus ( Site 0041)	Dresden	Sachsen
Germany	Universitaetsklinikum Erlangen ( Site 0044)	Erlangen	Bayern
Germany	SRH Wald-Klinikum Gera GmbH ( Site 0042)	Gera	Thuringen
Germany	Klinik fur Dermatologie Allergologie und Venerologie ( Site 0035)	Hannover	Baden-Wurttemberg
Germany	Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0033)	Kiel	Schleswig-Holstein
Germany	Universitaetsklinikum Leipzig ( Site 0040)	Leipzig	Sachsen
Germany	Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 0036)	Wuerzburg	Bayern
Israel	HaEmek Medical Center ( Site 0306)	Afula
Israel	Soroka Medical Center ( Site 0303)	Beer Sheva
Israel	Rambam Medical Center ( Site 0301)	Haifa
Israel	Hadassah Ein Karem Hebrew University Medical Center ( Site 0305)	Jerusalem
Israel	Rabin Medical Center ( Site 0302)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 0304)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0307)	Tel Aviv
Israel	Shamir Medical Center-Assaf Harofeh ( Site 0308)	Zerifin
Italy	ASST Papa Giovanni XXIII ( Site 0062)	Bergamo	Abruzzo
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0064)	Milano
Italy	Istituto Europeo di Oncologia ( Site 0067)	Milano
Italy	Istituto Nazionale Tumori Fondazione Pascale ( Site 0061)	Napoli
Italy	Istituto Oncologico Veneto ( Site 0063)	Padova
Italy	Azienda Ospedaliera Universitaria Senese ( Site 0065)	Siena	Toscana
Korea, Republic of	Kyungpook National University Chilgok Hospital ( Site 0553)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Samsung Medical Center ( Site 0551)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0554)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0552)	Seoul
Poland	Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0273)	Bydgoszcz	Kujawsko-pomorskie
Poland	Uniwersyteckie Centrum Kliniczne ( Site 0281)	Gdansk	Pomorskie
Poland	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0278)	Gliwice	Slaskie
Poland	Pratia MCM Krakow ( Site 0280)	Krakow	Malopolskie
Poland	Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0272)	Poznan	Wielkopolskie
South Africa	Sandton Oncology Medical Group PTY LTD ( Site 0802)	Johannesburg	Gauteng
South Africa	Cape Town Oncology Trials Pty Ltd ( Site 0803)	Kraaifontein	Western Cape
South Africa	Cancer Care Langenhoven Drive Oncology Centre ( Site 0805)	Port Elizabeth	Eastern Cape
Spain	Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 0182)	A Coruna	La Coruna
Spain	Hospital Clinic i Provincial Barcelona ( Site 0190)	Barcelona
Spain	Hospital Duran i Reinals ICO de Hospitalet ( Site 0187)	Hospitalet del Llobregat	Barcelona
Spain	Hospital Universitario Insular de Gran Canaria ( Site 0189)	Las Palmas de Gran Canaria	Las Palmas
Spain	Hospital General Universitario Gregorio Maranon ( Site 0191)	Madrid
Spain	Hospital Universitario La Paz ( Site 0184)	Madrid
Spain	Hospital Universitario Ramon y Cajal ( Site 0183)	Madrid
Spain	Hospital Universitario Carlos Haya ( Site 0186)	Malaga
Spain	Hospital Universitario Marques de Valdecilla ( Site 0181)	Santander	Cantabria
Sweden	Sahlgrenska Universitetssjukhuset ( Site 0212)	Goteborg	Vastra Gotalands Lan
Sweden	Laenssjukhuset Ryhov ( Site 0215)	Jonkoping	Jonkopings Lan
Sweden	Skanes Universitetssjukhus ( Site 0213)	Lund	Skane Lan
Sweden	Karolinska Universitetssjukhuset ( Site 0211)	Solna	Stockholms Lan
Sweden	Norrlands Universitetssjukhus ( Site 0216)	Umea	Vasterbottens Lan
Sweden	Akademiska Sjukhuset ( Site 0218)	Uppsala	Uppsala Lan
Sweden	Centrallasarettet Vaxjo ( Site 0214)	Vaxjo	Kronobergs Lan
Switzerland	Universitaetsspital Basel ( Site 0094)	Basel	Basel-Stadt
Switzerland	Kantonsspital Graubuenden ( Site 0091)	Chur	Grisons
Switzerland	Kantonsspital Winterthur ( Site 0095)	Winterthur	Zurich
Switzerland	Universitaetsspital Zuerich ( Site 0092)	Zuerich-Flughafen	Zurich
United Kingdom	Western General Hospital ( Site 0121)	Edinburgh	Edinburgh, City Of
United Kingdom	Guys and St Thomas NHS Foundation Trust ( Site 0126)	London	London, City Of
United Kingdom	Derriford Hospital ( Site 0129)	Plymouth
United Kingdom	Singleton Hospital ( Site 0131)	Swansea
United States	University of Colorado Cancer Center ( Site 0708)	Aurora	Colorado
United States	St. Vincent Frontier Cancer Center ( Site 0724)	Billings	Montana
United States	University of North Carolina - Cancer Hospital ( Site 0751)	Chapel Hill	North Carolina
United States	Inova Schar Cancer Institute ( Site 0739)	Fairfax	Virginia
United States	Minnesota Oncology Specialist, PA ( Site 0766)	Fridley	Minnesota
United States	Baptist MD Anderson Cancer Center ( Site 0767)	Jacksonville	Florida
United States	The Angeles Clinic and Research Institute ( Site 0707)	Los Angeles	California
United States	Atlantic Health System ( Site 0768)	Morristown	New Jersey
United States	Yale Cancer Center ( Site 0709)	New Haven	Connecticut
United States	Mid-Florida Cancer Centers ( Site 0764)	Orange City	Florida
United States	Valley Hospital ( Site 0749)	Paramus	New Jersey
United States	AMG Oncology ( Site 0714)	Park Ridge	Illinois
United States	Illinois Cancer Care, PC ( Site 0765)	Peoria	Illinois
United States	OHSU Center for Health & Healing ( Site 0731)	Portland	Oregon
United States	California Pacific Medical Center Research Institute ( Site 0705)	San Francisco	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0704)	San Francisco	California
United States	John Wayne Cancer Institute ( Site 0706)	Santa Monica	California

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Poland,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Per Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS is defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to approximately 46 months
Primary	Overall Survival (OS)	OS is defined as the time from date of randomization to date of death from any cause.	Up to approximately 46 months
Secondary	Objective Response Rate (ORR) as Assessed by BICR Per RECIST 1.1	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to approximately 46 months
Secondary	Duration of Response (DOR) as Assessed by BICR Per RECIST 1.1	For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the date of the first documented evidence of CR or PR until disease progression or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. Note: The appearance of one or more new lesions is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to approximately 46 months
Secondary	Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to approximately 46 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued any study treatment due to an AE is presented.	Up to approximately 46 months
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Global Health Status (GHS)/Quality of Life (QoL) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The GHS/QoL combined score consists of participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" GHS/QoL responses range in score from 0 to 100, with a higher score indicating a better outcome.	Baseline and Week 21
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Physical Function (PF) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest and needing help with eating, dressing, washing themselves or using the toilet]). For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome.	Baseline and Week 21
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 GHS/QoL Score	TTD is defined as the time from Baseline to 1st onset of a =10-point negative change (decrease) in EORTC-QLQ-C30 GHS Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. TThe GHS/QoL Score consists of participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" GHS/QoL responses range in score from 0 to 100, with a higher score indicating a better outcome. A longer TTD indicates a better outcome	Up to approximately 30 months
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 in Physical Function (PF) Score	TTD is defined as the time from Baseline to 1st onset of a =10-point negative change (decrease) in EORTC-QLQ-C30 PF Score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The PF Score consists of participant responses to questions regarding PF (5 questions about daily activities [strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves or using the toilet]. For PF, responses range in score from 0 to 100, with a higher score indicating a better outcome.	Up to approximately 30 months

External Links

•   Merck Clinical Trial Information