A Study of Napabucasin (BBI-608) in Combination With FOLFIRI in Adult Patients With Previously Treated Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

— CanStem303C  

Official title:

A Phase 3 Study of BBI-608 in Combination With 5-Fluorouracil, Leucovorin, Irinotecan (FOLFIRI) in Adult Patients With Previously Treated Metastatic Colorectal Cancer (CRC).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02753127
• Other study ID #: CanStem303C
• Secondary ID: BB608-303CRC2016
• Status: Completed
• Phase: Phase 3
• Start date: June 2016
• Est. completion date: May 12, 2021

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an international multi-center, prospective, open-label, randomized, adaptive design phase 3 trial of the cancer stem cell pathway inhibitor napabucasin plus standard bi-weekly FOLFIRI versus standard bi-weekly FOLFIRI in patients with previously treated metastatic colorectal cancer (CRC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1253
• Est. completion date: May 12, 2021
• Est. primary completion date: April 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable ICH guidelines and local and regulatory requirements prior to the performance of any study specific procedure.

2. Must have histologically confirmed advanced CRC that is metastatic.

3. Must have failed treatment with one regimen containing a fluoropyrimidine, oxaliplatin with or without bevacizumab for metastatic disease. All patients must have received a minimum of 6 weeks of the first-line regimen that included bevacizumab (if applicable), oxaliplatin and a fluoropyrimidine in the same cycle. Treatment failure is defined as radiologic progression during or < 6 months after the last dose of first-line therapy.

4. FOLFIRI therapy is appropriate for the patient and is recommended by the Investigator.

5. Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease performed within 21 days prior to randomization. Patients with either measurable disease or non-measurable evaluable disease are eligible.

6. Must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

7. Must be = 18 years of age.

8. For male or female patient of child bearing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days for female and male patients, of the final FOLFIRI dose. Patients who receive single agent napabucasin without FOLFIRI must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days for female patients and 90 days for male patients, of the final napabucasin dose.

9. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 5 days prior to randomization. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG.

10. Must have alanine transaminase (ALT) = 3 × institutional upper limit of normal (ULN) [= 5 × ULN in presence of liver metastases] within 14 days prior to randomization.

11. Must have hemoglobin (Hgb) = 9.0 g/dL within 14 days prior to randomization. Must not have required transfusion of red blood cells within 1 week of baseline Hgb assessment.

12. Must have total bilirubin = 1.5 × institutional ULN [= 2.0 x ULN in presence of liver metastases] within 14 days prior to randomization.

13. Must have creatinine = 1.5 × institutional ULN or Creatinine Clearance > 50 ml/min (as calculated by the Cockcroft-Gault equation (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) within 14 days prior to randomization.

14. Must have absolute neutrophil count = 1.5 x 10^9/L within 14 days prior to randomization.

15. Must have platelet count = 100 x 10^9/L within 14 days prior to randomization. Must not have required transfusion of platelets within 1 week of baseline platelet assessment.

16. Patient must have adequate nutritional status with Body Mass Index (BMI) > 18 kg/m^2 and body weight of > 40 kg with serum albumin > 3 g/dL.

17. Other baseline laboratory evaluations, listed in Section 6.0, must be done within 14 days prior to randomization.

18. Patient must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative formalin fixed paraffin block of tumor tissue in order that the specific biomarker assays may be conducted. Submission of the tissue is to occur prior to randomization, unless approved by the Sponsor. Where local center regulations prohibit submission of blocks of tumor tissue, two 2 mm cores of tumor from the block and 10-30 unstained slides of whole sections of representative tumor tissue are preferred. Where two 2 mm cores of tumor from the block are unavailable, 10-30 unstained slides of whole sections of representative tumor tissue alone are acceptable. Where no previously resected or biopsied tumor tissue exists or is available, on the approval of the Sponsor/designated CRO, the patient may still be considered eligible for the study.

19. Patient must consent to provision of a sample of blood in order that the specific correlative marker assays may be conducted.

20. Patients must be accessible for treatment and follow-up. Patients registered on this trial must receive protocol treatment and be followed at the participating center. This implies there must be reasonable geographical limits placed on patients being considered for this trial. Investigators must ensure that the patients randomized on this trial will be available for complete documentation of the treatment, response assessment, adverse events, and follow-up.

21. Protocol treatment is to begin within 2 calendar days of patient randomization.

22. The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.

Exclusion Criteria:

1. Anti-cancer chemotherapy or biologic therapy if administered prior to the first planned dose of study medication (napabucasin or FOLFIRI) within period of time equivalent to the usual cycle length of the regimen. An exception is made for oral fluoropyrimidines (e.g. capecitabine, S-1), where a minimum of 10 days since last dose must be observed prior to the first planned dose of study medication. Standard dose of bevacizumab (5 mg/kg) may be administered prior to FOLFIRI infusion, per Investigator decision, for as long as permanent decision to include or exclude bevacizumab is made prior to patient randomization. Radiotherapy, immunotherapy (including immunotherapy administered for non-malignant diseaseneoplastic treatment purposes), or investigational agents within four weeks of first planned dose of study medication, with the exception of a single dose of radiation up to 8 Gy (equal to 800 RAD) with palliative intent for pain control up to 14 days before randomization.

2. More than one prior chemotherapy regimen administered in the metastatic setting.

3. Major surgery within 4 weeks prior to randomization.

4. Patients with any known brain or leptomeningeal metastases are excluded, even if treated.

5. Women who are pregnant or breastfeeding. Women should not breastfeed while taking study treatment and for 4 weeks after the last dose of napabucasin or while undergoing treatment with FOLFIRI and for 180 days after the last dose of FOLFIRI.

6. Gastrointestinal disorder(s) which, in the opinion of the Qualified/Principal Investigator, would significantly impede the absorption of an oral agent (e.g. intestinal occlusion, active Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection).

7. Unable or unwilling to swallow napabucasin capsules daily.

8. Prior treatment with napabucasin.

9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

10. Known hypersensitivity to 5-fluorouracil/leucovorin

11. Known dihydropyrimidine dehydrogenase (DPD) deficiency

12. Known hypersensitivity to irinotecan

13. Chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis)

14. Patients receiving treatment with St. John's wort or Phenytoin.

15. Patients who plan to receive yellow fever vaccine during the course of the study treatment.

16. Abnormal glucuronidation of bilirubin, known Gilbert's syndrome

17. Patients with QTc interval > 470 milliseconds

18. For patients to be treated with a regimen containing bevacizumab:

• History of cardiac disease: congestive heart failure (CHF) > New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).

• Current uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management) as well as prior history of hypertensive crisis or hypertensive encephalopathy.

• History of arterial thrombotic or embolic events (within 6 months prior to study entry)

• Significant vascular disease (e.g., aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease)

• Evidence of bleeding diathesis or clinically significant coagulopathy

• Major surgical procedure (including open biopsy, significant traumatic injury, etc.) within 28 days, or anticipation of the need for major surgical procedure during the course of the study as well as minor surgical procedure (excluding placement of a vascular access device or bone marrow biopsy) within 7 days prior to study enrollment

• Proteinuria at screening as demonstrated by urinalysis with proteinuria = 2+ (patients discovered to have =2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate = 1g of protein in 24 hours to be eligible).

• History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months

• Ongoing serious, non-healing wound, ulcer, or bone fracture

• Known hypersensitivity to any component of bevacizumab

• History of reversible posterior leukoencephalopathy syndrome (RPLS)

• History of hypersensitivity to Chinese hamster ovary (CHO) cells or other human or humanized recombinant antibodies.

19. Patients with a history of other malignancies except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for > 3 years.

20. Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.

21. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Napabucasin
Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose).
• Fluorouracil

• Leucovorin

• Irinotecan

• Bevacizumab

Locations

Country	Name	City	State
Australia	Bankstown-Lidcombe Hospital	Bankstown	New South Wales
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	St Vincent's hospital Melbourne	Fitzroy	New South Wales
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Western Health	Melbourne	Victoria
Australia	Sunshine Coast Hospital and Health Service	Nambour	Queensland
Australia	Port Macquaries Base Hospital	Port Macquarie	New South Wales
Australia	Prince of Wales Hospital	Randwick
Australia	Goulburn Valley Health	Shepparton	Victoria
Australia	Gold Coast University Hosptial	Southport	Queensland
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Belgium	Imelda Ziekenhuis	Bonheiden	Antwerpen
Belgium	Imelda Ziekenhuis	Bonheiden	Antwerpen
Belgium	Imelda Ziekenhuis	Bonheiden	Antwerpen
Belgium	AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan	Brugge	West-Vlaanderen
Belgium	AZ Sint-Lucas - Campus Sint-Lucas	Brugge	West-Vlaanderen
Belgium	CHU de Liège - Domaine Universitaire du Sart Tilman	Bruxelles	Liège
Belgium	Hôpital Erasme	Bruxelles	Brussels Capital Region
Belgium	Grand Hôpital de Charleroi - Site Notre-Dame	Charleroi	Hainaut
Belgium	UZ Leuven - Campus Gasthuisberg	Leuven	Vlaams Brabant
Belgium	AZ Turnhout - Campus Sint-Elisabeth	Turnhout	Antwerpen
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Hopital Notre-Dame du CHUM	Montréal	Quebec
Canada	St. Mary's Hospital Center	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Saint Michael's Hospital Li Ka Shing Knowledge Institute	Toronto	Ontario
Canada	University of Toronto - Sunnybrook Health Sciences Centre	Toronto	Ontario
China	Beijing Cancer Hospital	Beijing
China	Henan Cancer Hospital	Henan
China	Jiangsu Province Hospital	Jiangsu
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Masarykuv onkologicky ustav	Brno
Czechia	FN Hradec Kralove	Hradec Králové	Královéhradecký Kraj
Czechia	Vseobecna fakultni nemocnice v Praze	Prague
France	Centre Paul Papin	Angers
France	Hospitalier Jean Minjoz	Besançon
France	Hôpital Morvan - CHRU de Brest - cancérologie et d'hématolog	Brest
France	CHU Estaing	Clermont Ferrand
France	Centre de Lutte Contre le Cancer (CLCC)	Dijon
France	CHU de Nantes - Hopital Hotel Dieu	Nantes
France	Hôpital Européen Georges Pompidou - Digestive Oncology	Paris
France	Hôpital Privé des Côtes d'Armor - Service oncologie	Plérin
France	Hospital of Poitiers	Poitiers
France	Centre Eugene Marquis	Rennes
France	Centre Rene Gauducheau	Saint-Herblain
Germany	Gesundheitszentrum Wetterau	Bad Nauheim
Germany	Charite - Campus Benjamin Franklin (Cbf)	Berlin
Germany	Charité Universitätsmedizin	Berlin
Germany	DRK Kliniken Berlin Koepenick	Berlin
Germany	MVZ Onkologischer Schwerpunkt am Oskar-Helene-Heim	Berlin
Germany	Vivantes Klinikum Am Urban	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden	Sachsen
Germany	Asklepios Klinik Altona	Hamburg
Germany	Facharztzentrum Eppendorf	Hamburg
Germany	Schwerpunkpraxis für Hämatologie und Onkologie	Magdeburg	Sachsen-Anhalt
Germany	Universitätsklinikum Marburg	Marburg
Germany	Leopoldina Krankenhaus Med. Klinik 2	Schweinfurt	Bayern
Germany	Medizinische Universitaetsklin	Ulm
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Israel	Ha'Emek Medical Center	Afula
Israel	The Barzilai Medical Center - Oncology Institute	Ashkelon
Israel	Soroka University Medical Center	Be'er Sheva
Israel	Shaare Zedek Medical center	Jerusalem
Israel	Meir Medical Center	Kefar Saba
Israel	Rabin MC - Oncology, Davidoff Center	Petah tikva
Israel	Ziv Medical Center (The Rebecca Sieff Hospital)	Safed
Israel	The Chaim Sheba Medical Centre - Division of Oncology	Tel HaShomer
Israel	Tel Aviv Sourasky Medical Center - Oncology	Tel-Aviv
Italy	Policlinico S.Orsola Malpighi, AOU di Bologna	Bologna
Italy	PO di Cremona, ASST di Cremona	Cremona
Italy	AUSL della Romagna, Osp. degli Infermi	Faenza	Ravenna
Italy	Ospedale Santa Maria del Prato	Feltre	Belluno
Italy	AO S. Martino, IRCCS, IST	Genova
Italy	Irccs Irst	Meldola	Forli
Italy	Ieo, Irccs	Milano
Italy	AOU Policlinico di Modena	Modena
Italy	Università degli studi della Campania "L.Vanvitelli"	Napoli
Italy	Ospedale Guglielmo da Saliceto, AUSL Piacenza	Piacenza
Italy	AOU Città della Salute e della Scienza di Torino - Molinette	Torino
Italy	AOU Ospedali Riuniti Umberto I - GM.Lanc	Torrette Di Ancona	Ancona
Japan	Medical Hospital, Tokyo Medical and Dental University	Bunkyo-ku	Tokyo
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Kyushu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	ST. Marianna University School of Medicine	Kawasaki	Kanagawa
Japan	Saitama Cancer Center	Kita-Adachi	Saitama
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	The cancer insitute hospital of JFCR (Japanese Foundation For Cancer Research)	Koto-ku	Tokyo
Japan	National Hospital Organization Shikoku Cancer Center	Matsunami	Ehime
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Osaka University Hospital	Suita	Osaka
Japan	Shizuoka Cancer Center	Sunto	Shizuoka
Japan	Osaka Medical College Hospital	Takatsuki	Osaka
Korea, Republic of	Yeungnam University Medical Center	Daegu	Daegu Gwang'yeogsi
Korea, Republic of	National Cancer Centre	Goyang	Gyeonggido
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Incheon Gwang'yeogsi
Korea, Republic of	Korea University Anam Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Korea University Guro Hospital	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggido
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Spaarne Gasthuis	Hoofddorp
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden	Friesland
Netherlands	Maastricht UMC	Maastricht
Netherlands	Elizabeth Tweesteden Ziekenhuis locatie Tilburg	Tilburg
Singapore	National Cancer Centre	Singapore	Central Singapore
Singapore	National University Cancer Institute	Singapore	Central Singapore
Singapore	Raffles Hospital	Singapore	Central Singapore
Spain	Complexo Hospital Universitario A Coruña	A Coruña	Galicia
Spain	Hospital Universitario Fundacion Alcorcon (HUFA)	Alcorcón	Madrid
Spain	Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Son Llatzer	Baleares
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Vall d'Hebrón	Barcelona
Spain	Consorci Hospital General Universitari Valencia (CHGUV)	Comunidad Valenciana	Valencia
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro-Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	H.U.V. del Rocío	Sevilla	Andalucía
Spain	Hospital Universitario Virgen de la Macarena	Sevilla
Spain	H.C.U.Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Michigan Cancer Center	Ann Arbor	Michigan
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Piedmont Cancer Institute, PC	Atlanta	Georgia
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Alabama Oncology	Birmingham	Alabama
United States	Dana Farber	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Roswell Park Cancer Center	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Texas Oncology - Dallas Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Texas Oncology - Denton South	Denton	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	City of Hope- Comprehensive Care Center	Duarte	California
United States	North Shore Hematology Oncology Associates	East Setauket	New York
United States	Northshore University Healthsystem	Evanston	Illinois
United States	US Oncology - Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Fort Belvoir Community Hospital	Fort Belvoir	Virginia
United States	Florida Cancer Specialists & Research Institute Fort Myers	Fort Myers	Florida
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Texas Oncology - Fort Worth	Fort Worth	Texas
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Indiana University Health Goshen Center for Cancer Care	Goshen	Indiana
United States	Saint Francis Cancer Treatment Center	Grand Island	Nebraska
United States	St Mary's Hospital & Regional Med Center	Grand Junction	Colorado
United States	Virginia Oncology Associates	Hampton	Virginia
United States	Memorial Cancer Institute at Memorial Hospital	Hollywood	Florida
United States	Millenium Oncology	Houston	Texas
United States	Research Medical Center	Kansas City	Missouri
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	University of California-San Diego/Moores UCSD Cancer Center	La Jolla	California
United States	Suburban Hematology-Oncology Associates, PC - Lawrenceville	Lawrenceville	Georgia
United States	Darthmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	West Cancer Center	Memphis	Tennessee
United States	Baptist Health Medical Group Oncology, LLC	Miami	Florida
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Michiana Hematology Oncology, PC	Mishawaka	Indiana
United States	Carol G. Simon Cancer Center	Morristown	New Jersey
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Weill Cornell Medical College	New York	New York
United States	Medical Oncology Hematology Consultants, PA	Newark	Delaware
United States	Northern Utah Associates	Ogden	Utah
United States	Cancer Research Network of Nebraska / Oncology Associates PC	Omaha	Nebraska
United States	Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Tennessee Oncology PLLC	Omaha	Nebraska
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	Texas Health Physicians Group	Plano	Texas
United States	Blue Ridge Cancer Care	Roanoke	Virginia
United States	Mayo Clinic Arizona	Rochester	Minnesota
United States	Missouri Baptist Medical Center ACCRU Network Site	Saint Louis	Missouri
United States	Sarah Cannon Research Institution	Saint Petersburg	Florida
United States	Texas Oncology-San Antonio	San Antonio	Texas
United States	UCLA Hematology Oncology Santa Monica	Santa Monica	California
United States	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Virginia Mason	Seattle	Washington
United States	Sanford Cancer Center	Sioux Falls	South Dakota
United States	Healthcare Research Network III, LLC	Tinley Park	Illinois
United States	Toledo Clinic Cancer Centers	Toledo	Ohio
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Northwest Cancer Specialists, P.C.	Vancouver	Washington
United States	Northwestern Medicine Cancer Center	Warrenville	Illinois
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Texas Oncology - Wichita Falls Texoma Cancer Center	Wichita Falls	Texas
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	Umass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  Czechia,  France,  Germany,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall survival was defined as the time from randomization until death from any cause.; Patients who are alive at the time of the interim or the final analyses or who have become lost to follow-up will be censored on the date the patient was last known to be alive.	Randomization to Date of Death from any cause or database cutoff date (28 Apr 2020) (Approximately 43 months)
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first objective documentation of disease progression per RECIST 1.1 (PD) or death, whichever comes first.	Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months)
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. The primary estimate of DCR will be based on patients with measurable disease by RECIST 1.1 at randomization	Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months)
Secondary	Objective Response Rate (ORR)	ORR is defined as the proportion of patients with a documented complete response and partial response (CR + PR) based on RECIST 1.1. The primary estimate for ORR will be based on patients with measurable disease by RECIST 1.1 at randomization.	Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months)
Secondary	Mean Change From Baseline for Global Health Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1).	The Quality of Life (QoL) of patients will be assessed using European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) (EORTC QLQ-30) while the patient remains on study treatment (FOLFIRI with or without BBI-608). EORTC QLQ-30 is used to assess the overall quality of life in cancer patients using 28 questions with a 4 point scale. (1 'Not at all' to 4'Very Much'); 2 questions use a 7-point sale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.	From baseline at Time 2 (Cycle 5 Day 1), approximately 57 days and Time 4 (Cycle 9 Day 1), approximately 113 days
Secondary	Mean Change From Baseline for Physical Functioning Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1).	The Quality of Life (QoL) of patients will be assessed using European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) (EORTC QLQ-30) while the patient remains on study treatment (FOLFIRI with or without BBI-608). EORTC QLQ-30 is used to assess the overall quality of life in cancer patients using 28 questions with a 4 point scale. (1 'Not at all' to 4'Very Much'); 2 questions use a 7-point sale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.	From baseline at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1)
Secondary	Number of Patients With Adverse Events in the General Population	All patients who have received at least one dose of either BBI-608 or FOLFIRI will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity.	All adverse event are collected from date of signed informed consent until 30 days after protocol treatment discontinuation. Outcome followed until study discontinuation up to 4 years