Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations
Study Details
Study Description
Brief Summary
This trial studies how well tucatinib works for solid tumors that make either more HER2 or a different type of HER2 than usual (HER2 alterations) The solid tumors studied in this trial have either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable).
All participants will get both tucatinib and trastuzumab. People with hormone-receptor positive breast cancer will also get a drug called fulvestrant.
The trial will also look at what side effects happen. A side effect is anything a drug does besides treating cancer.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
There are multiple cohorts in this trial:
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5 tumor specific cohorts with HER2 overexpression/amplification (cervical cancer, uterine cancer, biliary tract cancer, urothelial cancer, and non-squamous non-small cell lung cancer [NSCLC])
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2 tumor specific cohorts with HER2 mutations (non-squamous NSCLC and breast cancer)
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2 cohorts which will enroll all other HER2 amplified/overexpressed solid tumor types (except breast cancer, gastric or gastroesophageal junction adenocarcinoma [GEC], and colorectal cancer [CRC]) or HER2-mutated solid tumor types.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Tucatinib + Trastuzumab (+ Fulvestrant) Tucatinib + trastuzumab (+ fulvestrant in hormone-receptor positive HER2-mutant breast cancer only) |
Drug: tucatinib
300 mg orally twice daily
Other Names:
Drug: trastuzumab
Given into the vein (intravenously; IV). 8mg/kg IV on Cycle 1 Day 1, and 6mg/kg every 21 days starting on Cycle 2 Day 1
Other Names:
Drug: fulvestrant
Given into the muscle (intramuscular; IM) once every 4 weeks starting from Cycle 1 Day 1, plus one dose on Cycle 1 Day 15. Only administered to participants with hormone-receptor positive breast cancer.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Confirmed objective response rate (cORR) per investigator assessment [From start of treatment up to approximately 2 years]
cORR is defined as the proportion of participants with best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Secondary Outcome Measures
- Disease control rate (DCR) per investigator assessment [From start of treatment up to approximately 2 years]
DCR is defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease according to RECIST v1.1
- Duration of response (DOR) per investigator assessment [From start of treatment up to approximately 2 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 per RECIST v1.1 or death from any cause, whichever occurs first.
- Progression-free survival (PFS) per investigator assessment [From start of treatment up to approximately 2 years]
PFS is defined as the time from the date of treatment initiation to the date of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first.
- Overall survival (OS) [From start of treatment up to approximately 4 years]
OS is defined as the time from treatment initiation to death due to any cause.
- Incidence of adverse events (AEs) [From start of treatment up to approximately 2 years]
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 [From start of treatment up to approximately 2 years]
To be summarized using descriptive statistics.
- Incidence of dose alterations [From start of treatment up to approximately 2 years]
- Maximum concentration (Cmax) [Approximately 4 months, during first 6 cycles of treatment]
To be summarized using descriptive statistics.
- Trough concentration (Ctrough) [Approximately 4 months, during first 6 cycles of treatment]
To be summarized using descriptive statistics.
Eligibility Criteria
Criteria
Inclusion Criteria
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Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors
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Participants with non-squamous NSCLC must have progressed during or after standard treatment or for which no standard treatment is available
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Participants with other disease types must have progressed during or after ≥1 prior line of systemic therapy for locally-advanced unresectable or metastatic disease
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Disease progression during or after, or intolerance of, the most recent line of systemic therapy
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Disease demonstrating HER2 alterations (overexpression/amplification or HER2 activating mutations), as determined by local or central testing processed in a Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for
Standardization (ISO) accredited laboratory, according to one of the following:
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HER2 overexpression/amplification from fresh or archival tumor tissue or blood
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Known activating HER2 mutations detected in fresh or archival tumor tissue or blood
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Have measurable disease per RECIST v1.1 criteria according to investigator assessment
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Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Exclusion Criteria
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Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression.
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Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification may have received prior trastuzumab
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Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer
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History of exposure to a 360 mg/m² doxorubicin-equivalent or >720 mg/m^2 epirubicin-equivalent cumulative dose of anthracyclines
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Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial.
There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Arizona Oncology Associates, PC - HAL | Goodyear | Arizona | United States | 85395 |
2 | HonorHealth | Phoenix | Arizona | United States | 85016 |
3 | Mayo Clinic Arizona | Phoenix | Arizona | United States | 85054 |
4 | Arizona Cancer Center / University of Arizona | Tucson | Arizona | United States | 85724-5024 |
5 | UC San Diego / Moores Cancer Center | La Jolla | California | United States | 92093 |
6 | Pacific Shores Medical Group | Long Beach | California | United States | 90813 |
7 | Rocky Mountain Cancer Centers | Boulder | Colorado | United States | 80303 |
8 | Regional Cancer Care Associates | Manchester | Connecticut | United States | 06040 |
9 | Lombardi Cancer Center / Georgetown University Medical Center | Washington | District of Columbia | United States | 20007 |
10 | Mayo Clinic Florida | Jacksonville | Florida | United States | 32224 |
11 | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | United States | 33612 |
12 | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | United States | 33612 |
13 | University Cancer & Blood Center, LLC | Athens | Georgia | United States | 30607 |
14 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
15 | Mayo Clinic Rochester | Rochester | Minnesota | United States | 55905 |
16 | HealthPartners Institute | Saint Louis Park | Minnesota | United States | 55416 |
17 | Washington University in St Louis | Saint Louis | Missouri | United States | 63108 |
18 | Nebraska Cancer Specialists | Omaha | Nebraska | United States | 68130 |
19 | NYU Langone Hospital | Mineola | New York | United States | 11501 |
20 | NYU Langone Hospital | New York | New York | United States | 10016 |
21 | Mount Sinai Medical Center | New York | New York | United States | 10029 |
22 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
23 | Case Western Reserve University / University Hospitals Cleveland Medical Center | Cleveland | Ohio | United States | 44106 |
24 | James Cancer Hospital / Ohio State University | Columbus | Ohio | United States | 43210 |
25 | University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15213 |
26 | Prisma Health | Greenville | South Carolina | United States | 29605 |
27 | Tennessee Oncology-Nashville/Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
28 | Texas Oncology - West Texas | Abilene | Texas | United States | 79606 |
29 | Texas Oncology, P.A. - Dallas | Dallas | Texas | United States | 75246 |
30 | US Oncology Central Regulatory | The Woodlands | Texas | United States | 77380 |
31 | Texas Oncology - Waco | Waco | Texas | United States | 76712 |
32 | Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | United States | 84112 |
33 | Virginia Cancer Specialists, PC | Fairfax | Virginia | United States | 22031 |
34 | Seattle Cancer Care Alliance / University of Washington | Seattle | Washington | United States | 98109-1023 |
35 | Northwest Cancer Specialists, P.C. | Vancouver | Washington | United States | 98684 |
36 | Carbone Cancer Center / University of Wisconsin | Madison | Wisconsin | United States | 53792 |
37 | Cliniques Universitaires Saint Luc | Brussels | Other | Belgium | 1200 |
38 | Grand Hopital de Charleroi | Charleroi | Other | Belgium | 6000 |
39 | Universitair Ziekenhuis Antwerpen | Edegem | Other | Belgium | 2650 |
40 | Academisch Ziekenhuis Groeninge | Kortrijk | Other | Belgium | 8500 |
41 | CHU de Liege | Liege | Other | Belgium | 4000 |
42 | Istituto Europeo di Oncologia | Milano | Other | Italy | 20141 |
43 | Azienda Socio Sanitaria Territoriale di Monza. Ospedale San Gerardo | Monza | Other | Italy | 20900 |
44 | National Cancer Center Hospital | Chuo-ku | Other | Japan | 104-0045 |
45 | National Cancer Center Hospital East | Kashiwa-shi | Other | Japan | 277-8577 |
46 | St. Marianna University School of Medicine | Kawasaki-shi | Other | Japan | 2168511 |
47 | Aichi Cancer Center | Nagoya-shi | Other | Japan | 464-8681 |
48 | Kindai University Hospital | Osakasayama | Other | Japan | 589-8511 |
49 | The Cancer Institute Hospital of JFCR | Tokyo | Other | Japan | 135-8550 |
50 | Seoul National University Bundang Hospital | Seongnam-si | Other | Korea, Republic of | 13620 |
51 | Seoul National University Hospital | Seoul | Other | Korea, Republic of | 03080 |
52 | Samsung Medical Center | Seoul | Other | Korea, Republic of | 06351 |
53 | Severance Hospital, Yonsei University Health System | Seoul | Other | Korea, Republic of | 120-752 |
54 | Seoul National University Boramae Medical Center | Seoul | Other | Korea, Republic of | |
55 | Netherlands Cancer Institute | Amsterdam | Other | Netherlands | 1066 WX |
56 | Med Polonia Sp. z o. o. | Poznan | Other | Poland | 60-693 |
57 | Hospital Universitario Vall d'Hebron | Barcelona | Other | Spain | 08035 |
58 | L'Institut Catala d'Oncologia | L'Hospitalet de Llobregat | Other | Spain | 08908 |
59 | Hospital Universitario 12 de Octubre | Madrid | Other | Spain | 28041 |
60 | Hospital Clinico Universitario de Santiago de Compostela | Santiago de Compostela | Other | Spain | 15706 |
61 | Hospital Clinico Universitario de Valencia | Valencia | Other | Spain | 46010 |
62 | The Royal Marsden Hospital | London | Other | United Kingdom | SW3 6JJ |
63 | Sarah Cannon Research Institute UK | London | Other | United Kingdom | W1G 6AD |
64 | The Royal Marsden Hospital (Surrey) | Sutton | Other | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Seagen Inc.
Investigators
- Study Director: Jorge Ramos, DO, Seagen Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SGNTUC-019