A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer

Colorectal Neoplasms Clinical Trial

— MOUNTAINEER-03  

Official title:

An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05253651
• Other study ID #: SGNTUC-029
• Secondary ID: 2021-002672-40
• Status: Recruiting
• Phase: Phase 3
• Start date: October 24, 2022
• Est. completion date: April 30, 2028

Study information

• Verified date: June 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 866-333-7436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to find out if tucatinib with other cancer drugs works better than standard of care to treat participants with HER2 positive colorectal cancer. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease. Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable). Participants will be assigned randomly to the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either: - mFOLFOX6 alone, - mFOLFOX6 with bevacizumab, or - mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: April 30, 2028
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
• Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory
• If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatment
• HER2+ disease as determined by a tissue based assay performed at a central laboratory.
• Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
• Radiographically measurable disease per RECIST v1.1 with:
• At least one site of disease that is measurable and that has not been previously irradiated, or
• If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may

have any of the following:

• No evidence of brain metastases
• Previously treated brain metastases which are asymptomatic

Exclusion Criteria:

• Prior systemic anticancer therapy for colorectal cancer (CRC) in the metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.
• Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed >6 months prior to enrollment
• Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
• Previous treatment with anti-HER2 therapy
• Ongoing Grade 3 or higher neuropathy
• GI perforation within 12 months of enrollment

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• tucatinib
300mg given by mouth (orally) twice daily
• trastuzumab
8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.
• bevacizumab
5mg/kg given by IV every 2 weeks
• cetuximab
400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly
• oxaliplatin
85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.
• leucovorin
400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.
• levoleucovorin
200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.
• fluorouracil
400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.

Locations

Country	Name	City	State
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires	Other
Argentina	Instituto Alexander Fleming	Ciudad Autonoma Buenos Aires	Other
Argentina	CEMAIC - Centro Medico Privado	Cordoba	Other
Argentina	Instituto Oncologico de Cordoba	Córdoba	Other
Argentina	Centro de Investigacion Pergamino SA	Pergamino	Other
Argentina	Instituto Medico de la Fundacion Estudios Clinicos	Rosario	Other
Australia	St Vincent's Hospital Melbourne	Fitzroy	Other
Australia	The Alfred Hospital	Melbourne	Other
Australia	Townsville Cancer Center	Townsville	Other
Austria	Salzburg Cancer Research Institute	Salzburg	Other
Austria	Klinikum Wels-Grieskirchen GmbH	Wels	Other
Belgium	Institut Jules Bordet	Anderlecht	Other
Belgium	Cliniques Universitaires Saint Luc	Brussels	Other
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Other
Belgium	Hopital de Jolimont	Haine-Saint-Paul	Other
Belgium	Centre Hospitalier Chretien - Clinique MontLegia	Liège	Other
Belgium	Az Turnhout	Turnhout	Other
Brazil	Hospital de Cancer de Barretos - Fundacao Pio XII	Barretos	Other
Brazil	CIONC-Centro Integrado de Oncologia de Curitiba	Curitiba	Other
Brazil	Fundacao Doutor Amaral Carvalho	Jaú	Other
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	Other
Brazil	Instituto COI de Pesquisa	Rio de Janeiro	Other
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo Andre	Other
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	Sao Jose Rio Preto	Other
Brazil	ICESP - Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira	São Paulo	Other
Canada	Jewish General Hospital	Montreal	Quebec
Canada	University of Ottawa / Ottawa General Hospital	Ottawa	Ontario
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Chile	BIOCENTER Centro Clinico de Investigacion	Concepción	Other
Chile	Centro de Estudios Clinicos SAGA	Santiago	Other
Chile	Oncocentro APYS	Viña del Mar	Other
China	Beijing Cancer Hospital	Beijing	Other
China	Hunan Cancer Hospital	Changsha	Other
China	The Second Xiangya Hospital of Central South University	Changsha	Other
China	Changzhou Tumor Hospital	Changzhou	Other
China	The First People's Hospital of Changzhou	Changzhou	Other
China	Affiliated Hospital of Chengde Medical University	Chengde	Other
China	Army Specialty Medical Center of The Chinese People's Liberation Army	Chongqing	Other
China	900TH Hospital of Joint Logistics Support Force	Fuzhou	Other
China	Fujian Medical University Union Hospital	Fuzhou	Other
China	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Other
China	Hainan General Hospital	Haikou	Other
China	The Second Affiliated Hospital of Hainan Medical University	Haikou	Other
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Other
China	Zhejiang University School of Medicine	Hangzhou	Other
China	Harbin Medical University Cancer Hospital	Harbin	Other
China	Jinan Central Hospital	Jinan	Other
China	Shandong Cancer Hospital	Jinan	Other
China	The First Hospital Affiliated to Liaoning Medical College	Jinzhou	Other
China	The First Hospital of Lanzhou University	Lanzhou	Other
China	Linyi Cancer Hospital	Linyi	Other
China	Meizhou People's Hospital - Guangdong Province	Meizhou	Other
China	The First Affiliated Hospital of Nanchang University	Nanchang	Other
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Other
China	Nanyang Second General Hospital	Nanyang	Other
China	Shanghai General Hospital	Shanghai	Other
China	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Other
China	Liaoning Cancer Hospital and Institute	Shenyang	Other
China	The First Hospital of China Medical University	Shenyang	Other
China	The First Affiliated Hospital of Soochow University	Suzhou	Other
China	Shanxi Province Cancer Hospital	Taiyuan	Other
China	Tangshan People's Hospital	Tangshan	Other
China	Hubei Cancer Hospital	Wuhan	Other
China	Xuzhou Central Hospital	Xuzhou	Other
China	Henan Provincial People's Hospital	Zhengzhou	Other
France	Sainte Catherine Institut du Cancer Avignon Provence	Avignon	Other
France	Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz	Besancon Cedex	Other
France	CHU Brest Hopital Cavale Blanche	Brest
France	Center Georges Francois Leclerc	Dijon	Other
France	Hospital Edouard Herriot (HEH)	Lyon	Other
France	Hopital Saint Joseph de Marseille	Marseille	Other
France	Centre Hospitalier Universitaire Nantes-Hotel Dieu	Nantes	Other
France	Centre de Lutte contre le Cancer (CLCC) - Centre Antoine Lacassagne	Nice Cedex 2	Other
France	Hopital Europeen Georges Pompidou	Paris	Other
France	Hopital Saint-Antoine	Paris	Other
France	Hopital Saint Louis, APHP	Paris Cedex 10	Other
France	CHU Bordeaux Hopital Haut-Leveque	Pessac	Other
France	Centre Hospitalier Universitaire de Poitiers	Poitiers	Other
France	CHU de Rouen	Rouen	Other
France	CHU Saint Etienne Hopital Nord	Saint-Priest en Jarez	Other
France	Institut de Cancerologie de I'Ouest - Site Saint-Herblain	St Herblain	Other
France	Institut de cancerologie Strasbourg Europe	Strasbourg	Other
Germany	Gemeinschaftspraxis Haematologie - Onkologie: Freiberg-Richter, Jacobasch, Illmer, Wolf	Dresden	Other
Germany	Universitaetsklinikum Carl Gustav Carus Dresden	Dresden	Other
Germany	Medizinische Hochschule Hannover	Hannover	Other
Germany	Kliniken Maria Hilf GmbH	Mönchengladbach	Other
Germany	LMU - Klinikum der Universitaet Muenchen - Campus Grosshadern - Medizinische Klinik und Poliklinik III	München	Other
Greece	Evgenidion Clinic Agia Trias	Athens	Other
Hungary	Tolna Varmegyei Balassa Janos Korhaz	Szekszard	Other
Ireland	Bon Secours Hospital Cork	Cork	Other
Ireland	Beaumont Hospital	Dublin	Other
Ireland	Mater Misericordiae University Hospital (MMUH)	Dublin	Other
Ireland	Mater Private Hospital (MPH)	Dublin
Ireland	St Vincents University Hospital	Dublin 4	Other
Ireland	University Hospital Waterford	Waterford	Other
Ireland	Cork University Hospital	Wilton	Other
Italy	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione	Avellino
Italy	Fondazione Poliambulanza Istituto Ospedaliero	Brescia	Other
Italy	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi - Presido Ospedale Garibaldi - Nesima	Catania	Other
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	University of Foggia, Riuniti Hospital	Foggia	Other
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano	Other
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Other
Italy	Istituto Europeo di Oncologia	Milano	Other
Italy	Azienda Ospedaliera Universitaria Cagliari	Monserrato	Other
Italy	Universita degli studi della Campania Luigi Vanvitelli	Naploli	Other
Italy	Istituto Oncologico Veneto - IRCCS	Padova	Other
Italy	IRCSS Policlinico San Matteo	Pavia	Other
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Other
Italy	AUSL- IRCCS di Reggio Emilia	Reggio Emilia	Other
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCSU	Roma	Other
Italy	ASST Valtellina e Alto Lario	Sondrio	Other
Italy	Azienda Ospedaliera Cardinale Giovanni Panico	Tricase	Other
Italy	Azienda Ospedaliera Universitaria Integrata di Verona	Verona	Other
Japan	Chiba Cancer Center	Chiba	Other
Japan	National Cancer Center Hospital	Chuo-ku	Other
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Other
Japan	National Cancer Center Hospital East	Kashiwa-shi	Other
Japan	St. Marianna University School of Medicine	Kawasaki-shi	Other
Japan	Kagawa University Hospital	Kita-gun	Other
Japan	Saitama Cancer Center	Kitaadachi-gun	Other
Japan	Kobe City Hospital Organization Kobe City Medical Center General Hospital	Kobe-shi	Other
Japan	The Cancer Institute Hospital of JFCR	Koto-ku	Other
Japan	NHO Shikoku Cancer Center	Matsuyama-shi	Other
Japan	National Hospital Organization Osaka	Osaka-shi	Other
Japan	Osaka General Medical Center (Kyuseiki Sogo Iryo C)	Osaka-shi	Other
Japan	Kindai University Hospital	Osakasayama-Shi	Other
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo-shi	Other
Japan	Osaka University Hospital	Suita-shi	Other
Japan	Osaka Medical and Pharmaceutical University Hospital	Takatsuki-shi	Other
Japan	Kanagawa Cancer Center	Yokohama	Other
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Other
Korea, Republic of	Asan Medical Center - Oncology	Seoul	Other
Korea, Republic of	Korea University Anam Hospital	Seoul	Other
Korea, Republic of	Korea University Guro Hospital	Seoul	Other
Korea, Republic of	Samsung Medical Center	Seoul	Other
Korea, Republic of	Seoul National University Hospital	Seoul	Other
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Other
Netherlands	Netherlands Cancer Institute	Amsterdam	Other
Netherlands	St. Antonius Hospital	Nieuwegein	Other
Netherlands	VieCuri Medisch Centrum	Venlo	Other
Norway	Haukeland Universitetssjukehus	Bergen	Other
Norway	Oslo University Hospital	Oslo	Other
Poland	Katedra i Klinika Onkologii i Radioterapii	Gdansk	Other
Poland	Przychodnia Lekarska KOMED Roman Karaszewski	Konin	Other
Poland	Salve Medica	Lodz	Other
Poland	Mruk-Med - Sp. z o.o.	Rzeszow	Other
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warsaw	Other
Portugal	Hospital Sousa Martins	Guarda	Other
Portugal	The Champalimaud Centre for the Unknown	Lisboa	Other
Portugal	Centro Hospitalar Universitario do Porto - Hospital Geral de Santo Antonio	Porto	Other
Slovakia	Narodny Onkologicky Ustav	Bratislava	Other
Slovakia	POKO Poprad	Poprad	Other
Spain	Hospital General Universitario Alicante	Alicante	Other
Spain	Hospital Clinic de Barcelona	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Other
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	Barcelona	Other
Spain	Hospital Universitario Reina Sofia	Cordoba	Other
Spain	Hospital Universitari Arnau de Vilanova	Lleida	Other
Spain	Hospital General Universitario Gregorio Maranon	Madrid	Other
Spain	Hospital Universitario 12 de Octubre	Madrid	Other
Spain	Hospital Universitario La Paz	Madrid	Other
Spain	Hospital Universitario Ramon y Cajal Servicio de Oncologia Medica Oficina de Ensayos Clinicos	Madrid	Other
Spain	Hospital Regional Universitario de Malaga - Hospital General	Malaga	Other
Spain	Complejo Hospitalario Universitario de Ourense (CHOU)	Ourense	Other
Spain	Hospital Universitario Central de Asturias	Oviedo	Other
Spain	Complejo Hospitalario de Navarra	Pamplona	Other
Spain	Hospital Universitario Marques de Valdecilla	Santander	Other
Spain	Hospital Universitario Virgen del Rocio	Sevilla	Other
Spain	Consorci Hospital General Universitari de Valencia (CHGUV)	Valencia	Other
Spain	Hospital Universitario Miguel Servet	Zaragoza	Other
Switzerland	Kantonsspital Winterthur (KSW)	Winterthur	Other
Switzerland	Universitatsspital Zurich	Zurich	Other
Taiwan	Chang Gung Memorial Hospital - Kaohsiung	Kaohsiung City	Other
Taiwan	National Cheng-Kung University Hospital	Tainan	Other
Taiwan	National Taiwan University Hospital	Taipei	Other
Taiwan	Taipei Veterans General Hospital	Taipei City	Other
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan	Other
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol	Other
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge	Other
United Kingdom	Hull University Teaching Hospitals NHS Trust	Cottingham	Other
United Kingdom	Leeds Teaching Hospitals Trust	Leeds	Other
United Kingdom	Guy's and St Thomas' NHS Foundation	London	Other
United Kingdom	Imperial College Healthcare NHS Trust	London	Other
United Kingdom	The Christie NHS Foundation Trust	Manchester	Other
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne	Other
United States	Pacific Cancer Medical Center	Anaheim	California
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Gabrail Cancer Center Research, LLC	Canton	Ohio
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers - Aurora	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Providence Regional Medical Center Everett	Everett	Washington
United States	Palo Verde Cancer Specialists	Glendale	Arizona
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Kaiser Permanente Southern California	Los Angeles	California
United States	Los Angeles Cancer Network	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Texas Oncology - McKinney	McKinney	Texas
United States	MidAmerica Cancer Center, LLC	Merriam	Kansas
United States	Mount Sinai Medical Center / Florida	Miami Beach	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Southern California	Newport Beach	California
United States	Texas Oncology - Northeast Texas	Paris	Texas
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	FirstHealth of the Carolinas	Pinehurst	North Carolina
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Roanoke	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	HealthPartners Institute	Saint Louis Park	Minnesota
United States	Providence Medical Foundation	Santa Rosa	California
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Northwest Cancer Specialists, P.C.	Vancouver	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Portugal,  Slovakia,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR)	The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause	Up to approximately 3 years
Secondary	Overall survival (OS)	The time from randomization to death from any cause	Up to approximately 6 years
Secondary	Confirmed objective response rate (cORR) per RECIST v1.1 by BICR	The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by BICR	Up to approximately 3 years
Secondary	PFS per RECIST v1.1 by investigator assessment	The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause	Up to approximately 3 years
Secondary	cORR per RECIST v1.1 by investigator assessment	The proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators	Up to approximately 3 years
Secondary	Duration of response (DOR) per RECIST v1.1 by BICR	The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause	Up to approximately 3 years
Secondary	DOR per RECIST v1.1 by investigator assessment	The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause	Up to approximately 3 years
Secondary	Time to second progression or death (PFS2)	The time from randomization to disease progression on the next-line of therapy, or death from any cause	Up to approximately 3 years
Secondary	Incidence of adverse events (AEs)	Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	Through 30 days after the last study treatment; approximately 1 year
Secondary	Incidence of dose alterations		Through 30 days after the last study treatment; approximately 1 year
Secondary	Trough concentration (Ctrough)	PK parameter	Approximately 4 months
Secondary	Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score	Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/quality of life (QoL) scales, higher scores indicate better functioning or global health status/quality of life (QoL). For symptom scales, higher scores indicate greater symptom burden.	Through 30-37 days after the last study treatment; approximately 1 year
Secondary	Time to meaningful change in EORTC QLQ30 score	The time from baseline to the first onset of a =10-point changes in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100.; For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.	Through 30-37 days after the last study treatment; approximately 1 year