Neoplasms

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Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

89Zr-AMG211

89-ZrAMG211 PET

E. G.E. de Vries, MD, PhD

AMG 211 is a bispecific single-chain antibody construct of the bispecific T-cell engager (BiTE®) class that targets human carcinoembryonic antigen (CEA, CD66e) on (tumor) cells and cluster of differentiation 3 (CD3) positive T-cells. AMG 211 is a potentially new targeted drug in the treatment of relapsed/refractory gastrointestinal adenocarcinoma, since those are CEA expressing tumors. A well-known challenge in current drug development using targeted therapies is the high level of heterogeneity of target expression that is present in specific tumor types. Radio-labeling of AMG 211 with the positron emission tomography (PET) radionuclide Zirconium-89 (89Zr) enables non-invasive imaging and quantification of AMG 211 distribution in cancer patients. By performing a 89Zr-AMG211 PET scan prior to treatment with AMG 211, the uptake of the tracer in the primary and metastatic tumor lesions and normal organ distribution can be evaluated. By performing a 89Zr-AMG211 PET scan during AMG 211 continuous intravenous (cIV) treatment the investigators will be able to evaluate the impact of prolonged steady state exposure of AMG 211 on tumor and tissue uptake. The 89Zr-AMG211 PET imaging study may help to identify patients more likely to benefit from AMG 211 therapy.

89Zr-AMG211 PET Imaging Study

89Zr-AMG211 PET Imaging in Patients With Relapsed/Refractory Gastrointestinal Adenocarcinoma Before and During Treatment With AMG 211

University Medical Center Groningen

MSC_apceth_101

To evaluate the safety and tolerability of MSC_apceth_101.

Treatment of Advanced Gastrointestinal Cancer in a Phase I/II Trial With Modified Autologous MSC_apceth_101

Apceth GmbH & Co. KG

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Bevacizumab

Leucovorin

Fluorouracil

Irinotecan

Capecitabine

Levoleucovorin

Folic Acid

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

BBI608 is administered orally twice daily, continuously. Oxaliplatin 85 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2 over 46-48 hours) continuous intravenous infusion. This regimen will be repeated every 14 days thereafter.

BBI608 is administered orally twice daily, continuously. Oxaliplatin 85 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2 over 46-48 hours) continuous intravenous infusion. Bevacizumab 5 mg/kg will be administered intravenously following oxaliplatin/leucovorin infusion. This regimen will be repeated every 14 days thereafter.

BBI608 is administered orally twice daily, continuously. CAPOX regimen will be administered orally (capecitabine) and IV (oxaliplatin). Capecitabine 850 mg/m\^2 will be administered orally twice-daily for 14 consecutive days and be repeated every 21 days. Oxaliplatin will be administered IV and be repeated every 21 days thereafter. If capecitabine is tolerated at the 850 mg/m\^2 twice daily dose, dosage may be increased to 1000 mg/m\^2 twice daily as tolerated after the first cycle.

BBI608 is administered orally twice daily, continuously. Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated every 14 days thereafter.

BBI608 is administered orally twice daily, continuously. Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. Bevacizumab 5 mg/kg will be administered intravenously following oxaliplatin/leucovorin infusion. This regimen will be repeated every 14 days thereafter.

BBI608 is administered orally twice daily, continuously. Regorafenib 120 mg will be administered orally once daily, with a low-fat meal and be continued for 21 consecutive days of every 28 days thereafter. If regorafenib is tolerated in the first cycle, dosage may be increased to 160 mg once daily as tolerated after the first cycle.

BBI608 is administered orally twice daily, continuously. Irinotecan 180 mg/m\^2 will be administered intravenously. This regimen will be repeated every 14 days thereafter.

BBI608

Regorafenib

Boston Biomedical

This is an open label, multi-center, Phase 1/2 dose escalation study of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan.

This is an open label, multi-center, Phase 1/2 dose escalation study of BBI608 administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan. A study cycle will consist of daily and continuous oral administration of BBI608 for four weeks (28 days) in combination with FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan.

A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer

A Phase Ib/II Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer

Assessment of safety of napabucasin administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan in participants with advanced gastrointestinal malignancies by reporting of adverse events and serious adverse events

Assessment of the objective response rate (ORR) of napabucasin administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. The Objective Response Rate (ORR) is the proportion of participants with a complete response or partial response who have measurable disease at baseline imaging.

To determine the maximum concentration of napabucasin and the area under the plasma concentration vs. time curve of napabucasin when administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib.

To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin

To determine the anti-tumor activity (specifically the disease control rate) of napabucasin administered in combination with either FOLFOX6 with and without bevacizumab, or CAPOX, or FOLFIRI with and without bevacizumab, or regorafenib, or irinotecan. Percentage of participants with a documented complete response, partial response and stable disease based on RECIST 1.1.

To determine the disease control rate of napabucasin administered in combination with FOLFIRI in patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. Percentage of participants with a documented complete response, partial response and stable disease based on RECIST 1.1.

The effect of napabucasin given in combination with FOLFIRI on Progression Free Survival (PFS) of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer. PFS of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer.

The effect of napabucasin given in combination with FOLFIRI on Overall Survival (OS) of patients with FOLFIRI/XELIRI-refractory metastatic colorectal cancer.

Sumitomo Pharma America, Inc.

All participants who received at least 1 dose of napabucasin administered orally, twice daily, in combination with FOLFOX6 regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously starting on Day 1 of Cycle 1, after the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous intravenous (IV) infusion.

Napabucasin Plus FOLFOX6

All participants who received at least 1 dose of napabucasin administered orally, twice daily, in combination with FOLFOX6 plus bevacizumab regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously over 2 hours starting on Day1 of Cycle 1, following the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous IV infusion. Bevacizumab 5 mg/kg was administered intravenously following the oxaliplatin/leucovorin infusion.

Napabucasin Plus FOLFOX6 Plus Bevacizumab

All participants who received at least 1 dose of napabucasin administered orally, twice daily, in combination with CAPOX regimen. The CAPOX regimen was administered orally (capecitabine) and by IV (oxaliplatin). Starting on Day 1 of Cycle 1, capecitabine 850 mg/m2 was administered orally BID following the first daily dose of napabucasin for 14 consecutive days and repeated every 21 days. Oxaliplatin 130 mg/m2 was administered intravenously over 2 hours, following the first daily dose of napabucasin starting on Day 1 of Cycle 1 and repeated every 21 days thereafter. If capecitabine was tolerated at the 850 mg/m2 BID dose, the dosage could have been increased to 1000 mg/m2 BID as tolerated after the first cycle.

Napabucasin Plus CAPOX

All participants who received at least 1 dose of napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter.

Napabucasin Plus FOLFIRI

All participants who received at least 1 dose of napabucasin administered orally, twice daily, in combination with FOLFIRI plus bevacizumab regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5 FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. Bevacizumab 5 mg/kg was administered intravenously following the irinotecan/leucovorin infusion. This regimen was repeated every 14 days thereafter.

Napabucasin Plus FOLFIRI Plus Bevacizumab

All participants who received at least 1 dose of napabucasin administered orally, twice daily, in combination with regorafenib 120 mg, administered orally once daily with a low-fat meal, starting on Day 1 of Cycle 1 for 21 consecutive days of every 28 days thereafter. If regorafenib was tolerated in the first cycle, the dosage could have been increased to 160 mg once daily as tolerated after the first cycle.

Napabucasin Plus Regorafenib

All participants who received at least 1 dose of napabucasin administered orally, twice daily, in combination with irinotecan 180 mg/m2, administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. This regimen was repeated every 14 days thereafter.

Napabucasin Plus Irinotecan

All participants who were enrolled to Arm A to receive napabucasin administered orally, twice daily, in combination with FOLFOX6 regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously starting on Day 1 of Cycle 1, after the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous intravenous (IV) infusion.

All participants who were enrolled to Arm B to receive napabucasin administered orally, twice daily, in combination with FOLFOX6 plus bevacizumab regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously over 2 hours starting on Day1 of Cycle 1, following the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous IV infusion. Bevacizumab 5 mg/kg was administered intravenously following the oxaliplatin/leucovorin infusion.

All participants who were enrolled to Arm C to receive napabucasin administered orally, twice daily, in combination with CAPOX regimen. The CAPOX regimen was administered orally (capecitabine) and by IV (oxaliplatin). Starting on Day 1 of Cycle 1, capecitabine 850 mg/m2 was administered orally BID following the first daily dose of napabucasin for 14 consecutive days and repeated every 21 days. Oxaliplatin 130 mg/m2 was administered intravenously over 2 hours, following the first daily dose of napabucasin starting on Day 1 of Cycle 1 and repeated every 21 days thereafter. If capecitabine was tolerated at the 850 mg/m2 BID dose, the dosage could have been increased to 1000 mg/m2 BID as tolerated after the first cycle.

All participants who were enrolled to Arm D to receive napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter.

All participants who were enrolled to Arm E to receive napabucasin administered orally, twice daily, in combination with FOLFIRI plus bevacizumab regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5 FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. Bevacizumab 5 mg/kg was administered intravenously following the irinotecan/leucovorin infusion. This regimen was repeated every 14 days thereafter.

All participants who were enrolled to Arm F to receive napabucasin administered orally, twice daily, in combination with regorafenib 120 mg, administered orally once daily with a low-fat meal, starting on Day 1 of Cycle 1 for 21 consecutive days of every 28 days thereafter. If regorafenib was tolerated in the first cycle, the dosage could have been increased to 160 mg once daily as tolerated after the first cycle.

All participants who were enrolled to Arm G to receive napabucasin administered orally, twice daily, in combination with irinotecan 180 mg/m2, administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. This regimen was repeated every 14 days thereafter.

Total

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black

Native Hawaiian or Other Pacific Islander

White

Other

Race/Ethnicity, Customized

Tegan Nguyen

Napabucasin administered orally, twice daily, in combination with FOLFOX6 regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously starting on Day 1 of Cycle 1, after the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous intravenous (IV) infusion. Patients included in this group received at least one dose of study drug.

Napabucasin administered orally, twice daily, in combination with FOLFOX6 plus bevacizumab regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously over 2 hours starting on Day1 of Cycle 1, following the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous IV infusion. Bevacizumab 5 mg/kg was administered intravenously following the oxaliplatin/leucovorin infusion. Patients included in this group received at least one dose of study drug.

Napabucasin administered orally, twice daily, in combination with CAPOX regimen. The CAPOX regimen was administered orally (capecitabine) and by IV (oxaliplatin). Starting on Day 1 of Cycle 1, capecitabine 850 mg/m2 was administered orally BID following the first daily dose of napabucasin for 14 consecutive days and repeated every 21 days. Oxaliplatin 130 mg/m2 was administered intravenously over 2 hours, following the first daily dose of napabucasin starting on Day 1 of Cycle 1 and repeated every 21 days thereafter. If capecitabine was tolerated at the 850 mg/m2 BID dose, the dosage could have been increased to 1000 mg/m2 BID as tolerated after the first cycle. Patients included in this group received at least one dose of study drug.

Napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter. Patients included in this group received at least one dose of study drug.

Napabucasin administered orally, twice daily, in combination with FOLFIRI plus bevacizumab regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5 FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. Bevacizumab 5 mg/kg was administered intravenously following the irinotecan/leucovorin infusion. This regimen was repeated every 14 days thereafter. Patients included in this group received at least one dose of study drug.

Napabucasin administered orally, twice daily, in combination with regorafenib 120 mg, administered orally once daily with a low-fat meal, starting on Day 1 of Cycle 1 for 21 consecutive days of every 28 days thereafter. If regorafenib was tolerated in the first cycle, the dosage could have been increased to 160 mg once daily as tolerated after the first cycle. Patients included in this group received at least one dose of study drug.

Napabucasin administered orally, twice daily, in combination with irinotecan 180 mg/m2, administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. This regimen was repeated every 14 days thereafter. Patients included in this group received at least one dose of study drug.

Number of Participants With Adverse Events and Serious Adverse Events

Napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter . Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

Analysis limited to a subset of group D in which patients had FOLFIRI/XELIRI refractory metastatic colorectal cancer. Patients in this subgroup also had a baseline scan and at least 1 disease assessment following the initiation of therapy.

The Objective Response Rate of Napabucasin Administered in Combination in FOLFIRI in Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer

Sponsor's decision to terminate further development of the napabucasin program. Data collection and analysis were therefore not conducted as planned.

Determination of the Maximum Observed Concentration (Cmax) and Area Under the Plasma Concentration vs. Time Curve (AUClast)

No on-treatment biopsies were performed therefore no pharmacodynamic testing on tumor tissue was conducted.

Pharmacodynamics

Napabucasin administered orally, twice daily, in combination with FOLFOX6 regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously starting on Day 1 of Cycle 1, after the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous intravenous (IV) infusion. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

All participants who were enrolled to Arm B to receive napabucasin administered orally, twice daily, in combination with FOLFOX6 plus bevacizumab regimen administered every 14 days. The regimen consisted of oxaliplatin 85 mg/m2 together with leucovorin 400 mg/m2 administered intravenously over 2 hours starting on Day1 of Cycle 1, following the first daily dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following oxaliplatin/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2 over 46-48 hours) by continuous IV infusion. Bevacizumab 5 mg/kg was administered intravenously following the oxaliplatin/leucovorin infusion. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

All participants who were enrolled to Arm C to receive napabucasin administered orally, twice daily, in combination with CAPOX regimen. The CAPOX regimen was administered orally (capecitabine) and by IV (oxaliplatin). Starting on Day 1 of Cycle 1, capecitabine 850 mg/m2 was administered orally BID following the first daily dose of napabucasin for 14 consecutive days and repeated every 21 days. Oxaliplatin 130 mg/m2 was administered intravenously over 2 hours, following the first daily dose of napabucasin starting on Day 1 of Cycle 1 and repeated every 21 days thereafter. If capecitabine was tolerated at the 850 mg/m2 BID dose, the dosage could have been increased to 1000 mg/m2 BID as tolerated after the first cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

All participants who were enrolled to Arm D to receive napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

All participants who were enrolled to Arm E to receive napabucasin administered orally, twice daily, in combination with FOLFIRI plus bevacizumab regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5 FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. Bevacizumab 5 mg/kg was administered intravenously following the irinotecan/leucovorin infusion. This regimen was repeated every 14 days thereafter. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

All participants who were enrolled to Arm F to receive napabucasin administered orally, twice daily, in combination with regorafenib 120 mg, administered orally once daily with a low-fat meal, starting on Day 1 of Cycle 1 for 21 consecutive days of every 28 days thereafter. If regorafenib was tolerated in the first cycle, the dosage could have been increased to 160 mg once daily as tolerated after the first cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

All participants who were enrolled to Arm G to receive napabucasin administered orally, twice daily, in combination with irinotecan 180 mg/m2, administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. This regimen was repeated every 14 days thereafter. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.

Patients who received at least 1 cycle of study treatment and had at least 1 disease assessment following the initiation of therapy. Patients missing imaging assessment following the initiation of treatment are not included in the assessment for DCR.

Disease Control Rate

Patients with FOLFIRI/XELIRI refractory metastatic colorectal cancer who received at least 1 cycle of study treatment and had at least 1 disease assessment following the initiation of therapy. Patients missing imaging assessment following the initiation of treatment are not included in the assessment for DCR.

Disease Control Rate of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer

Napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter. Patients in this group had a baseline scan and at least one on study scan or died from any cause.

Analysis limited to a subset of group D in which patients had FOLFIRI/XELIRI refractory metastatic colorectal cancer. Patients in this subgroup also had a baseline scan and at least 1 on study scan or died from any cause.

Progression Free Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer

Napabucasin administered orally, twice daily, in combination with FOLFIRI regimen. Irinotecan 180 mg/m2 together with leucovorin 400 mg/m2 was administered intravenously starting on Day 1 of Cycle 1, following the first dose of napabucasin. A 5-FU 400 mg/m2 bolus was administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m2/day (total 2400 mg/m2) by continuous infusion. This regimen was repeated every 14 days thereafter . The patients in this subgroup were assessed to have FOLFIRI/XELIRI refractory metastatic colorectal cancer prior to enrollment.

Analysis limited to a subset of group D in which patients had FOLFIRI/XELIRI refractory metastatic colorectal cancer.

Overall Survival of Patients With FOLFIRI/XELIRI-refractory Metastatic Colorectal Cancer

Overall Study

home-based exercise intervention:

Endurance training (moderate intensity; walking), 3-5 times per week Patients will receive exercise counselling how to realize the planned intervention home-based. Further, they will be asked to fill out an exercise log. The study team will periodically review adherence to the intervention and identify problems.

The wait list control group receives usual care over the study period. Usual care depends on the hospital guidelines as well as oncologists' and physicians' consideration.

Endurance training (moderate intensity; walking), 3-5 times per week Patients will receive exercise counselling how to realize the planned intervention home-based. Further, they will be asked to fill out an exercise log. The study team will periodically review adherence to the intervention and identify problems.

home-based exercise intervention

Winfried Banzer, Prof.

The study is a randomized controlled trial with the aim to examine the feasibility and the effects of a home-based exercise intervention program on activities of daily living (ADL) in patients with advanced gastrointestinal cancer undergoing chemotherapeutic treatment. Further outcomes include functional and body status, quality of life, body composition, and chemotherapy completion rate. Study participants will be randomized to an exercise intervention group or a wait-list control group

A randomised longitudinal study. A total of 44 gastrointestinal cancer patients before their first-line chemotherapy are recruited and randomised into one of two treatment groups A: Home based- physical activity or B: wait-control. The intervention period is 12 weeks. Primary outcome are the ADLs (iADL 1-8; FIM 1-7).Secondary outcomes are the physical activity, quality of life, peripheral polyneuropathy, chemotherapy regimen, gait speed, postural stability, maximal isometric voluntary force of the upper extremity, Maximal isometric voluntary force (MIVF) and strength endurance of the lower extremity, nutritional state, body composition and perceive functional ability. All measurements are standardized and are performed before chemotherapy, after 2 cycles of chemotherapy (4-6weeks) and after 12 weeks.

Physical Function and Activities of Daily Living in Cancer Patients During Chemotherapy

Only pseudonymised data without the plan to share

Short battery of physical performance tests used to assess lower extremity function. Balance, gait, strength, and endurance are evaluated.

Measuring the sensibility with a Rydel-Seiffer tuning fork

The maximal isometric voluntary force (MIVF) of the randomly chosen knee extensor is measured with a strain gauge force transducer (ASYS®; SPOREG; 100 Hz) in a standardised seating position (predefined knee and hip angle = 90°).

For the five times sit to stand test patients start in a standard position sitting on a chair that is placed next to the wall with the arms folded across their chest. They are asked to stand up from a chair to a full standing position and sit down again keeping the arms crossed for five times as quickly as possible.

European Organisation for Research and Treatment of Cancer (EORTC_QLQ-C30)

The 36-Items Short Form Health Survey (SF-36)

multifrequent bioelectrical impedance analysis (DATA-Input) measuring the phase angle

multifrequent bioelectrical impedance analysis (DATA-Input) measuring the body cell mass (BCM)

multifrequent bioelectrical impedance analysis (DATA-Input) measuring the fat mass

Functional Independence Measurement (FIM) Questionnaire

- instrumental Activity of Daily Living (iADL)

Agaplesion Markus Krankenhaus gGmbH

Goethe University

Head of Department

Part 1 - This first study phase will involve interviewing 24 patients to ask for their feedback on the appropriateness of questions being developed for use in the narrative interviewing in part 2 of the study. The cognitive interview will be audio-recorded. Demographics and ECOG performance status will be recorded prior to the cognitive interview.

As outlined ECOG performance status will be recorded at the time of registration without the subject's involvement. Quality of life, treatment satisfaction, distress and peacefulness will also be recorded at baseline. Subjects will neither be shown the goals-of-care (GOC) video nor undergo the narrative interview process - they will be contacted as per re-assessment.

As outlined ECOG performance status will be recorded at the time of registration without the subject's involvement. Quality of life, treatment satisfaction, distress and peacefulness will also be recorded at baseline. Subjects will be shown the goals-of-care (GOC) video but not undergo a narrative interview process - they will be contacted as per re-assessment.

As outlined ECOG performance status will be recorded at the time of registration without the subject's involvement. Quality of life, treatment satisfaction, distress and peacefulness will also be recorded at baseline. subjects will watch the goals-of-care (GOC) video (described in detail in the next paragraph) and then be given the narrative question stem vetted/assessed in part 1 including any changes made to that stem in the process of Part 1 testing. Subjects in P-COCC arm will then be contacted for a telephone interview and audio-taping of their narrative. Interviews will be semi- structured and based off the narrative stem that subjects were previously given for review. Interviews will last approximately 30-45 minutes and will be conducted by staff from the MSKCC Department of Psychiatry \& Behavioral Sciences.

Part 1 participants will be scheduled for their single pilot interview. There are no additional assessments.

single pilot interview

Subjects will be shown the goals-of-care (GOC) video but not undergo a narrative interview process - they will be contacted as per re-assessment.

goals-of-care (GOC) video

subjects will watch the goals-of-care (GOC) video (described in detail in the next paragraph) and then be given the narrative question stem vetted/assessed in part 1 including any changes made to that stem in the process of Part 1 testing. Subjects in P-COCC arm will then be contacted for a telephone interview and audio-taping of their narrative. Interviews will be semi- structured and based off the narrative stem that subjects were previously given for review. Interviews will last approximately 30-45 minutes and will be conducted by staff from the MSKCC Department of Psychiatry \& Behavioral Sciences,

goals-of-care (GOC) video and narrative question

Subjects in the usual care arm will neither be given the narrative stem nor watch the video.

usual care

Will be a proof-of-concept, small scale, RCT to measure P-COCC acceptability and other quantitative and qualitative effects. Seventy five participants will be randomized to Usual Care, Video, or Video and Interview.

Part 2 Andrew Epstein, MD

This study is being done to get individuals' feedback on advanced care planning and decision making.

This study is divided into two parts (Part 1 and Part 2). The purpose of Part 1 is to survey people to find out what is important to people with advanced cancer (again, their values, such as their goals, concerns and sources of support). This has never been done before in the way the investigators are doing it, and that is why this is called a "pilot" study, which is where a new method or treatment is being created and evaluated.

The purpose of Part 2 is to see if combining a medical options video with a short interview about values helps people with how they feel about their medical situation, and what they know about their medical options for their medical situation.

Person-Centered Oncology Care and Choices (P-COCC): Piloting and Initial Randomized Testing of a Combined Values Narrative Interview and Video Education Advance Care Planning Program in Gastrointestinal Oncology Patients

primary outcome is assessed in Part 2 of the study, and is acceptability of this newly- developed P-COCC intervention, as measured by subjects in P-COCC arm who will complete three Likert scale questions examining the degree to which they found the narrative recording process.

pre-post scoring on our various psychometric questionnaires (quantitative) and of the subject responses during narrative interviewing (qualitative)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
89Zr-AMG211 PET Imaging Study	NCT02760199	Advanced Gastro...	89Zr-AMG211 89-ZrAMG211 PET	18 Years -	University Medical Center Groningen
89Zr-AMG211 PET Imaging Study	NCT02760199	Advanced Gastro...	89Zr-AMG211 89-ZrAMG211 PET	18 Years -	University Medical Center Groningen
Treatment of Advanced Gastrointestinal Cancer in a Phase I/II Trial With Modified Autologous MSC_apceth_101	NCT02008539	Advanced Gastro...	MSC_apceth_101	18 Years -	Apceth GmbH & Co. KG
A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Advanced Gastrointestinal Cancer	NCT02024607	Advanced Gastro...	BBI608 Fluorouracil Oxaliplatin Leucovorin Irinotecan Bevacizumab Capecitabine Regorafenib	18 Years -	Sumitomo Pharma America, Inc.
Physical Function and Activities of Daily Living in Cancer Patients During Chemotherapy	NCT02677129	Advanced Gastro...	home-based exer...	50 Years -	Goethe University
Treatment of Advanced Gastrointestinal Cancer in a Phase I/II Trial With Modified Autologous MSC_apceth_101	NCT02008539	Advanced Gastro...	MSC_apceth_101	18 Years -	Apceth GmbH & Co. KG
Person-Centered Oncology Care and Choices (P-COCC): Piloting and Initial Randomized Testing of a Combined Values Narrative Interview and Video Education Advance Care Planning Program in Gastrointestinal Oncology Patients	NCT01912131	Advanced Gastro...	single pilot in... goals-of-care (... goals-of-care (... usual care Part 2	18 Years -	Memorial Sloan Kettering Cancer Center
Physical Function and Activities of Daily Living in Cancer Patients During Chemotherapy	NCT02677129	Advanced Gastro...	home-based exer...	50 Years -	Goethe University

Spots Global Cancer Trial Database for advanced gastrointestinal cancer