Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
- Conditions
- GEJ AdenocarcinomaCholangiocarcinomaGallbladder CarcinomaColorectal CarcinomaEsophageal AdenocarcinomaGastric Adenocarcinoma
- Interventions
- Registration Number
- NCT04430738
- Lead Sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Brief Summary
This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. It will also look at whether tucatinib works with these drugs to treat certain types of cancer.
The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach, intestines, or gallbladder (gastrointestinal cancer).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 41
-
Participants must have an unresectable or metastatic solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below:
-
Cohorts 1A, 1B, 1C, and 1D
- CRC
- Gastric adenocarcinoma
- GEJ adenocarcinoma
- Esophageal adenocarcinoma
- Cholangiocarcinoma
- Gallbladder carcinoma
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Cohorts 1E, 1F, 1G, and 2A
- Gastric adenocarcinoma
- GEJ adenocarcinoma
- Esophageal adenocarcinoma
-
Cohort 2B
- CRC
-
-
Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment for all cohorts, except Cohort 1G.
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HER2+ disease, as determined by historic or local laboratory testing
-
Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 as determined by the investigator
-
Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the investigator
-
Eastern Cooperative Oncology Group Performance Status score of 0 or 1.
- History of known hypersensitivity to planned study treatment
- Known to be positive for Hepatitis B or C
- For Cohorts 2A and 2B: prior anti-HER2 therapies
- For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
There are additional inclusion criteria. The study center will determine if criteria for participations are met.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1B trastuzumab Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1A tucatinib Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1A oxaliplatin Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1A fluorouracil Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1B tucatinib Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1C trastuzumab Tucatinib + trastuzumab + CAPOX given in 21-day cycles Cohort 1D tucatinib Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days Cohort 1A trastuzumab Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1C tucatinib Tucatinib + trastuzumab + CAPOX given in 21-day cycles Cohort 1D oxaliplatin Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days Cohort 1E fluorouracil Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles Cohort 2A capecitabine Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 1F pembrolizumab Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 1F tucatinib Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2A leucovorin Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2A fluorouracil Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 1G pembrolizumab Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2A tucatinib Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2A oxaliplatin Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2B oxaliplatin Tucatinib + trastuzumab + FOLFOX given in 14-day cycles. Cohort 1D fluorouracil Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days Cohort 1A leucovorin Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1B oxaliplatin Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1B fluorouracil Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1B leucovorin Tucatinib + trastuzumab + FOLFOX given in 14-day cycles Cohort 1C oxaliplatin Tucatinib + trastuzumab + CAPOX given in 21-day cycles Cohort 1C capecitabine Tucatinib + trastuzumab + CAPOX given in 21-day cycles Cohort 1D trastuzumab Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days Cohort 1D leucovorin Tucatinib + trastuzumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles and trastuzumab given every 21 days Cohort 1E leucovorin Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles Cohort 1E tucatinib Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles Cohort 1E trastuzumab Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles Cohort 1E oxaliplatin Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles Cohort 1F trastuzumab Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 1E pembrolizumab Tucatinib + trastuzumab + pembrolizumab + FOLFOX. Tucatinib and FOLFOX given in 14-day cycles, trastuzumab given in 21-day cycles, and pembrolizumab given in 42-day cycles Cohort 1F oxaliplatin Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 1F capecitabine Tucatinib + trastuzumab + pembrolizumab + CAPOX. Tucatinib, trastuzumab, and CAPOX given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 1G tucatinib Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 1G trastuzumab Tucatinib + trastuzumab + pembrolizumab. Tucatinib and trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2A trastuzumab Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2A pembrolizumab Tucatinib + trastuzumab + pembrolizumab + (FOLFOX or CAPOX). Either (1) tucatinib and FOLFOX given in 14-day cycles or (2) tucatinib and CAPOX given in 21-day cycles. Trastuzumab given in 21-day cycles and pembrolizumab given in 42-day cycles. Cohort 2B tucatinib Tucatinib + trastuzumab + FOLFOX given in 14-day cycles. Cohort 2B trastuzumab Tucatinib + trastuzumab + FOLFOX given in 14-day cycles. Cohort 2B fluorouracil Tucatinib + trastuzumab + FOLFOX given in 14-day cycles. Cohort 2B leucovorin Tucatinib + trastuzumab + FOLFOX given in 14-day cycles.
- Primary Outcome Measures
Name Time Method Incidence of laboratory abnormalities (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B) Up to approximately 12 months Incidence of DLTs (Cohorts 1C, 1D, 1E, 1F, and 1G) Up to approximately 12 months Incidence of dose alterations (Cohort 1D) Up to approximately 12 months Incidence of renal dose-limiting toxicities (DLTs) (Cohorts 1A and 1B) Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days) Incidence of adverse events (AEs) (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B) Up to approximately 12 months An AE is defined as 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.
- Secondary Outcome Measures
Name Time Method PK parameter of oxaliplatin - AUClast (Cohorts 1A and 1B) Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days) To be summarized using descriptive statistics
Duration of response (DOR) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A) Up to approximately 2.5 years DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression or death from any cause, whichever occurs first.
Overall survival (OS) (Cohort 1C, 1E, 1F, 1G, and 2A) Up to approximately 2.5 years OS is defined as the time from treatment initiation to death due to any cause
Objective response rate (ORR) (Cohorts 1C, 1E, 1F, and 1G) Up to approximately 2.5 years ORR is defined as the proportion of subjects with confirmed CR or PR, according to RECIST v1.1.
Incidence of AEs (Cohorts 1A and 1B) Up to approximately 12 months An AE is defined as 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.
Incidence of laboratory abnormalities (Cohorts 1A and 1B) Up to approximately 12 months Change in glomerular filtration rate (GFR) from baseline through 2 cycles of combination therapy (Cohorts 1A and 1B) Up to approximately 6 weeks To be summarized using descriptive statistics
PK parameter of tucatinib - Tmax (Cohorts 1A and 1B) Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days) To be summarized using descriptive statistics
PK parameter of oxaliplatin - Cmax (Cohorts 1A and 1B) Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days) To be summarized using descriptive statistics
Pharmacokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A and 1B) Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days) To be summarized using descriptive statistics
PK parameter of tucatinib - Cmax (Cohorts 1A and 1B) Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days) To be summarized using descriptive statistics
PK parameter of tucatinib - Ctrough (Cohorts 1A, 1B, 1C, 1E, 1F, and 1G) Up to approximately 2.5 months; through predose of Cycle 6, Day 1 To be summarized using descriptive statistics
PK parameter of oxaliplatin - Tmax (Cohorts 1A and 1B) Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days) To be summarized using descriptive statistics
Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (Cohort 2A) Up to approximately 2.5 years cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR)
Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A) Up to approximately 2.5 years PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause, which occurs first.
Trial Locations
- Locations (28)
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
University of Colorado Denver CTO(CTRC)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
🇺🇸Aurora, Colorado, United States
PCM Trials
🇺🇸Denver, Colorado, United States
Sibley Memorial Hospital
🇺🇸Washington, District of Columbia, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Siteman Cancer Center - North County
🇺🇸Florissant, Missouri, United States
Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - St Peters
🇺🇸Saint Peters, Missouri, United States
University of New Mexico Comprehensive Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Duke University Medical Center, Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Aichi Cancer Center Hospital
🇯🇵Nagoya, Aichi, Japan
St. Marianna University Hospital
🇯🇵Kawasaki, Kanagawa, Japan
Cancer Institute Hospital of Japanese Foundation for Cancer Research.
🇯🇵Koto-ku, Tokyo, Japan
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba, Japan
Osaka International Cancer Institute
🇯🇵Osaka-shi, Osaka, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan