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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04471428




Registration number
NCT04471428
Ethics application status
Date submitted
7/07/2020
Date registered
15/07/2020
Date last updated
30/05/2024

Titles & IDs
Public title
Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy
Scientific title
A Phase III, Multicenter, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Atezolizumab Given in Combination With Cabozantinib Versus Docetaxel Monotherapy in Patients With Metastatic Non-Small Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy
Secondary ID [1] 0 0
GO41892
Universal Trial Number (UTN)
Trial acronym
CONTACT-01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cabozantinib
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Docetaxel

Experimental: Atezolizumab + Cabozantinib - Participants received atezolizumab on Day 1 of each 21-day cycle and cabozantinib orally once daily on Days 1-21 of each cycle.

Active Comparator: Docetaxel - Participants received docetaxel on Day 1 of each 21-day cycle.


Treatment: Drugs: Cabozantinib
Cabozantinib will be administered orally, once daily at a dose of 40 mg on Days 1-21 of each cycle.

Treatment: Drugs: Atezolizumab
Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

Treatment: Drugs: Docetaxel
Docetaxel will be administered by IV infusion at a starting dose of 75mg/m2 on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) as Determined by Investigator
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [2] 0 0
Confirmed Objective Response Rate (ORR) as Determined by Investigator
Timepoint [2] 0 0
Up to approximately 24 months
Secondary outcome [3] 0 0
Duration of Response (DOR) as Determined by Investigator
Timepoint [3] 0 0
Up to approximately 24 months
Secondary outcome [4] 0 0
Time to Confirmed Deterioration in Patient-Reported Physical Functioning (PF)
Timepoint [4] 0 0
Up to approximately 24 months
Secondary outcome [5] 0 0
Time to Confirmed Deterioration in Patient-Reported Global Health Status (GHS)
Timepoint [5] 0 0
Up to approximately 24 months
Secondary outcome [6] 0 0
PFS Rates Assessed by Investigator
Timepoint [6] 0 0
6 months and 1 year
Secondary outcome [7] 0 0
OS Rates
Timepoint [7] 0 0
1 and 2 years
Secondary outcome [8] 0 0
Percentage of Participants With Adverse Events
Timepoint [8] 0 0
From signing the informed consent form up to the study completion date: 28 February 2024 (i.e., approximately 41 months)
Secondary outcome [9] 0 0
Minimum Serum Concentration (Cmin) of Atezolizumab
Timepoint [9] 0 0
Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle is 21 days)
Secondary outcome [10] 0 0
Maximum Serum Concentration (Cmax) of Atezolizumab
Timepoint [10] 0 0
Postdose on Day 1 of Cycle 1 (each cycle is 21 days)
Secondary outcome [11] 0 0
Minimum Plasma Concentration (Cmin) of Cabozantinib
Timepoint [11] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)
Secondary outcome [12] 0 0
Maximum Plasma Concentration (Cmax) of Cabozantinib
Timepoint [12] 0 0
Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)
Secondary outcome [13] 0 0
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Timepoint [13] 0 0
Predose on Day 1 of Cycles 1,2,3,4,8,12 and 16 (each cycle is 21 days) and at post-treatment follow-up visit (= 30 days after final dose)

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed metastatic NSCLC

- Documented radiographic disease progression during or following treatment with
platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered
concurrently or sequentially for metastatic NSCLC

- Measurable disease per RECIST v1.1 outside CNS as assessed by investigator

- Known PD-L1 status or availability of tumor tissue for central PD-L1 testing

- ECOG Performance Status score of 0 or 1

- Recovery to baseline or Grade <=1 NCI CTCAE v5.0 from toxicities related to any prior
treatments, unless adverse events are clinically nonsignificant and/or stable on
supportive therapy in the opinion of the investigator

- Adequate hematologic and end-organ function

- Negative HIV test at screening

- Negative hepatitis B surface antigen (HBsAg) test at screening

- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total
HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening

- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
test followed by a negative HCV RNA test at screening

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception, and agreement to refrain from donating
eggs,

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive methods, and agreement to refrain from donating sperm.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy with the following agents for NSCLC: Cabozantinib, Docetaxel,
Combination of an anti-PD-L1/PD-1 antibody concurrently with a vascular endothelial
growth factor (VEGF)R targeting tyrosine kinase inhibitor (TKI)

- Treatment with investigational therapy within 28 days prior to initiation of study
treatment

- Documentation of known sensitizing mutation in the EGFR gene or ALK fusion oncogene

- Patients with known ROS1 rearrangements, BRAF V600E mutations, or other actionable
oncogenes with approved therapies if available

- Symptomatic, untreated, or actively progressing CNS metastases

- History of leptomeningeal disease

- Uncontrolled tumor-related pain

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (more frequently than once monthly)

- Severe hepatic impairment

- Uncontrolled or symptomatic hypercalcemia

- Any other active malignancy at the time of initiation of study treatment or diagnosis
of another malignancy within 3 years prior to initiation of study treatment that
requires active treatment, except for locally curable cancers that have been
apparently cured, such as basal or squamous cell skin cancer, incidental prostate
cancer, or carcinoma in situ of the prostate, cervix, or breast

- Stroke, transient ischemic attack, myocardial infarction or other symptomatic ischemic
events within 6 months of initiation of study treatment

- Significant vascular disease within 6 months of initiation of study treatment

- Significant cardiovascular disease within 3 months prior to initiation of study
treatment, unstable arrhythmia, or unstable angina

- Active tuberculosis

- Severe infection within 4 weeks prior to initiation of study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia, or any active infection that, in the opinion on the investigator, could
impact patient safety

- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
of study treatment

- Current treatment with anti-viral therapy for HBV

- Major surgical procedure, other than for diagnosis within 4 weeks prior to initiation
of study treatment, or anticipation of need for a major surgical procedure during the
study

- Pregnant or lactating females, or intention of becoming pregnant during the treatment
with atezolizumab in combination with cabozantinib in the experimental arm or during
the treatment with docetaxel in the control arm, or within 5 months after the final
dose of atezolizumab and/or 4 months after the final dose of cabozantinib, whichever
is later.

- Ongoing Grade >= 2 sensory or motor neuropathy

- Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, granulomatosis with polyangiitis, Sjögren syndrome, Guillain-Barré
syndrome, or multiple sclerosis with the following exceptions: Patients with a history
of autoimmune-mediated hypothyroidism who are on thyroid replacement hormone are
eligible for the study. Patients with controlled Type 1 diabetes mellitus are eligible
for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo
with dermatologic manifestations only are eligible for the study provided all of
following conditions are met: Rash must cover < 10% of body surface area.

- Pharmacologically uncompensated, symptomatic hypothyroidism

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan

- Prior allogeneic stem cell or solid organ transplantation

- Administration of a live, attenuated vaccine within 4 weeks prior to initiation of
study treatment or anticipation of need for such a vaccine during atezolizumab
treatment or within 5 months after the final dose of atezolizumab

- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2) within 4 weeks or 5 drug-elimination half-lives
(whichever is longer) prior to initiation of study treatment

- Treatment with systemic immunosuppressive medication within 2 weeks prior to
initiation of study treatment, or anticipation of need for systemic immunosuppressive
medication during study treatment, with the following exceptions: Patients who
received acute, low-dose systemic immunosuppressant medication or a one-time pulse
dose of systemic immunosuppressant medication are eligible for the study after Medical
Monitor confirmation has been obtained. Patients who received mineralocorticoids,
inhaled or low-dose systemic corticosteroids for COPD or asthma, or low-dose
corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for
the study.

- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins

- Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation

- Known allergy or hypersensitivity to any component of the cabozantinib formulation

- History of severe hypersensitivity to docetaxel or to other drugs formulated with
polysorbate 80

- Concomitant anticoagulation with coumarin agents, direct thrombin inhibitor
dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors

- History of risk factors for torsades de pointes

- Corrected QT interval corrected through use of Fridericia's formula (QTcF) > 480 ms
per ECG within 14 days before initiation of study treatment

- Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic
BP > 90 mm Hg despite optimal antihypertensive treatment

- Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute
obstruction of the pancreatic or biliary duct, appendicitis, cholangitis,
cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel
disease

- Abdominal fistula, bowel obstruction, GI perforation, or intra-abdominal abscess
within 6 months before initiation of study treatment

- Known cavitating pulmonary lesion(s) or known endobronchial disease manifestation

- Lesions invading major pulmonary blood vessels

- Clinically significant hematuria, hematemesis, hemoptysis of > 0.5 teaspoon (2.5 mL)
of red blood, coagulopathy, or other history of significant bleeding within 3 months
before initiation of study treatment

- Serious non-healing wound/ulcer/bone fracture

- Malabsorption syndrome

- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency, or glucose-galactose malabsorption are also excluded.

- Requirement for hemodialysis or peritoneal dialysis

- Inability to swallow tablets

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2024
Actual
Sample size
Target
Accrual to date
Final
366
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital; Oncology - St. Leonards
Recruitment hospital [2] 0 0
Townsville Hospital - Townsville
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Austin Hospital Olivia Newton John Cancer Centre - Heidelberg
Recruitment hospital [5] 0 0
Affinity Oncology - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
4810 - Townsville
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Austria
State/province [11] 0 0
Graz
Country [12] 0 0
Austria
State/province [12] 0 0
Linz
Country [13] 0 0
Austria
State/province [13] 0 0
Rankweil
Country [14] 0 0
Austria
State/province [14] 0 0
Salzburg
Country [15] 0 0
Austria
State/province [15] 0 0
Wien
Country [16] 0 0
Belgium
State/province [16] 0 0
Anderlecht
Country [17] 0 0
Belgium
State/province [17] 0 0
Bruxelles
Country [18] 0 0
Belgium
State/province [18] 0 0
Gent
Country [19] 0 0
Belgium
State/province [19] 0 0
Namur
Country [20] 0 0
France
State/province [20] 0 0
Amiens
Country [21] 0 0
France
State/province [21] 0 0
Angers
Country [22] 0 0
France
State/province [22] 0 0
Grenoble
Country [23] 0 0
France
State/province [23] 0 0
Limoges
Country [24] 0 0
France
State/province [24] 0 0
Marseille
Country [25] 0 0
France
State/province [25] 0 0
Montpellier
Country [26] 0 0
France
State/province [26] 0 0
Mulhouse
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
Germany
State/province [28] 0 0
Bad Berka
Country [29] 0 0
Germany
State/province [29] 0 0
Essen
Country [30] 0 0
Germany
State/province [30] 0 0
Gießen
Country [31] 0 0
Germany
State/province [31] 0 0
Hannover
Country [32] 0 0
Germany
State/province [32] 0 0
Köln
Country [33] 0 0
Germany
State/province [33] 0 0
Marburg
Country [34] 0 0
Germany
State/province [34] 0 0
Paderborn
Country [35] 0 0
Greece
State/province [35] 0 0
Athens
Country [36] 0 0
Greece
State/province [36] 0 0
Heraklion
Country [37] 0 0
Greece
State/province [37] 0 0
Thessaloniki
Country [38] 0 0
Italy
State/province [38] 0 0
Campania
Country [39] 0 0
Italy
State/province [39] 0 0
Emilia-Romagna
Country [40] 0 0
Italy
State/province [40] 0 0
Friuli-Venezia Giulia
Country [41] 0 0
Italy
State/province [41] 0 0
Lazio
Country [42] 0 0
Italy
State/province [42] 0 0
Liguria
Country [43] 0 0
Italy
State/province [43] 0 0
Lombardia
Country [44] 0 0
Italy
State/province [44] 0 0
Puglia
Country [45] 0 0
Italy
State/province [45] 0 0
Toscana
Country [46] 0 0
Japan
State/province [46] 0 0
Hyogo
Country [47] 0 0
Japan
State/province [47] 0 0
Miyagi
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Tokyo
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Cheongju si
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Goyang-si
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Gyeonggi-do
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Gyeongsangnam-do
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Incheon
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Seongnam-si
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Seoul
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Ulsan
Country [58] 0 0
Poland
State/province [58] 0 0
Bydgoszcz
Country [59] 0 0
Poland
State/province [59] 0 0
Bytom
Country [60] 0 0
Poland
State/province [60] 0 0
Gliwice
Country [61] 0 0
Poland
State/province [61] 0 0
Koszalin
Country [62] 0 0
Poland
State/province [62] 0 0
Otwock
Country [63] 0 0
Portugal
State/province [63] 0 0
Lisboa
Country [64] 0 0
Portugal
State/province [64] 0 0
Porto
Country [65] 0 0
Portugal
State/province [65] 0 0
Vila Nova de Gaia
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Jaroslavl
Country [67] 0 0
Russian Federation
State/province [67] 0 0
Moskovskaja Oblast
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Sankt Petersburg
Country [69] 0 0
Spain
State/province [69] 0 0
LA Coruña
Country [70] 0 0
Spain
State/province [70] 0 0
Barcelona
Country [71] 0 0
Spain
State/province [71] 0 0
Madrid
Country [72] 0 0
Spain
State/province [72] 0 0
Sevilla
Country [73] 0 0
Spain
State/province [73] 0 0
Valencia
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Cambridge
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Glasgow
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Huddersfield
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Exelixis
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase III, multicenter, randomized, open-label study designed to evaluate the
efficacy, safety, and pharmacokinetics of atezolizumab given in combination with cabozantinib
compared with docetaxel monotherapy in patients with metastatic NSCLC, with no sensitizing
EGFR mutation or ALK translocation, who have progressed following treatment with
platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or
sequentially.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04471428
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04471428