Clinical trial NCT04430738: Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
Official title: A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Colorectal Carcinoma
Gastric Adenocarcinoma
GEJ Adenocarcinoma
Esophageal Adenocarcinoma
Cholangiocarcinoma
Gallbladder Carcinoma
Keywords: HER2+
HER2-positive
CRC
Gastric cancer
Esophageal cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-12
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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
  * 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.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Incidence of renal dose-limiting toxicities (DLTs) (Cohorts 1A and 1B)
timeFrame: Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days)
measure: Incidence of adverse events (AEs) (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)
timeFrame: Up to approximately 12 months
measure: Incidence of laboratory abnormalities (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B)
timeFrame: Up to approximately 12 months
measure: Incidence of DLTs (Cohorts 1C, 1D, 1E, 1F, and 1G)
timeFrame: Up to approximately 12 months
measure: Incidence of dose alterations (Cohort 1D)
timeFrame: Up to approximately 12 months
Secondary outcomes:
measure: Incidence of AEs (Cohorts 1A and 1B)
timeFrame: Up to approximately 12 months
measure: Incidence of laboratory abnormalities (Cohorts 1A and 1B)
timeFrame: Up to approximately 12 months
measure: Change in glomerular filtration rate (GFR) from baseline through 2 cycles of combination therapy (Cohorts 1A and 1B)
timeFrame: Up to approximately 6 weeks
measure: Pharmacokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A and 1B)
timeFrame: Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
measure: PK parameter of tucatinib - Cmax (Cohorts 1A and 1B)
timeFrame: Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
measure: PK parameter of tucatinib - Ctrough (Cohorts 1A, 1B, 1C, 1E, 1F, and 1G)
timeFrame: Up to approximately 2.5 months; through predose of Cycle 6, Day 1
measure: PK parameter of tucatinib - Tmax (Cohorts 1A and 1B)
timeFrame: Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days)
measure: PK parameter of oxaliplatin - AUClast (Cohorts 1A and 1B)
timeFrame: Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
measure: PK parameter of oxaliplatin - Cmax (Cohorts 1A and 1B)
timeFrame: Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
measure: PK parameter of oxaliplatin - Tmax (Cohorts 1A and 1B)
timeFrame: Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days)
measure: Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (Cohort 2A)
timeFrame: Up to approximately 2.5 years
measure: Duration of response (DOR) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)
timeFrame: Up to approximately 2.5 years
measure: Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A)
timeFrame: Up to approximately 2.5 years
measure: Overall survival (OS) (Cohort 1C, 1E, 1F, 1G, and 2A)
timeFrame: Up to approximately 2.5 years
measure: Objective response rate (ORR) (Cohorts 1C, 1E, 1F, and 1G)
timeFrame: Up to approximately 2.5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Aurora
country: United States
facility: University of Colorado Denver CTO(CTRC)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)
state: Colorado
city: Denver
country: United States
facility: PCM Trials
state: Colorado
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Florissant
country: United States
facility: Siteman Cancer Center - North County
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: Durham
country: United States
facility: Duke University Medical Center, Duke Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center Investigational Pharmacy
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Kawasaki
country: Japan
facility: St. Marianna University Hospital
state: Kanagawa
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of Japanese Foundation for Cancer Research.
state: Tokyo
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: