A Phase 2 interventional study of Cetuximab and Laboratory Biomarker Analysis in Head and Neck Squamous Cell Carcinoma and Recurrent Head and Neck Carcinoma, sponsored by National Cancer Institute (NCI). Completed at 24 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-12-19.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
This randomized phase II trial studies how well cetuximab with or without tivantinib works in treating patients with head and neck cancer that has come back (recurrent), has spread to other places in the body (metastatic), or cannot be removed by surgery. Monoclonal antibodies, such as cetuximab, may interfere with the ability of tumor cells to grow and spread. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cetuximab is more effective with or without tivantinib in treating patients with head and neck cancer.
PRIMARY OBJECTIVES:
I. Response rate (comparing the cetuximab/ARQ 197 [tivantinib] combination with cetuximab single agent activity).
SECONDARY OBJECTIVES:
I. Continuous tumor shrinkage. II. Progression-free survival (PFS). III. Overall survival (OS). IV. Objectives I, II, and III above, as well as response rates, will be assessed and compared between treatment arms in the subgroup of patients with high mesenchymal epithelial transition factor (c-MET) expression, and/or high c-MET copy number.
V. Single agent activity for ARQ 197 (tivantinib) in patients who have failed cetuximab.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15 and tivantinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 81 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients receive cetuximab IV over 60-120 minutes on days 1 and 15 and tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Biological: Cetuximab · Other: Laboratory Biomarker Analysis · Drug: Tivantinib
Patients receive cetuximab IV over 60-120 minutes on days 1 and 15. Patients who fail cetuximab as a single agent may receive single agent tivantinib PO BID on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Biological: Cetuximab · Other: Laboratory Biomarker Analysis
Given IV
Correlative studies
Given PO
Overall Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 1 year
c-MET Copy Number
Change in copy number from baseline to 8 weeks
Time frame: Baseline to 8 weeks
c-MET Expression
Change in c-MET expression from baseline to 8 weeks
Time frame: Baseline to 8 weeks
Change in Tumor Burden
Early change in tumor burden measured using the sum of longest diameters of target lesions, expressed as percent change from baseline.
Time frame: Baseline to 8 weeks
Overall Survival
Time from randomization until death or date last known alive
Time frame: Up to 5 years
Progression-free Survival
Time from randomization until disease progression/death from any cause or date last know progression-free
Time frame: Up to 3 years
Overall Response Rate of Single-agent Tivantinib After Failure of Cetuximab
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 1 year
Number of Participants With Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab
Non-serious adverse events, CTCAE (4.0)
Time frame: Up to 3 years
Number of Patients With Serious Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab
CTCAE (4.0)
Time frame: 3 years
| Milestone | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) |
|---|---|---|
| Started | 42 | 39 |
| Completed | 40 | 38 |
| Not completed | 2 | 1 |
| Withdrew: Protocol violation | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Milestone | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) |
|---|---|---|
| Started | 0 | 15 |
| Completed | 0 | 15 |
| Not completed | 0 | 0 |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
| Participants | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) |
|---|---|---|
| Complete response | 1 | 0 |
| Partial response | 2 | 3 |
Change in copy number from baseline to 8 weeks
No measurements were reported for this outcome.
Change in c-MET expression from baseline to 8 weeks
No measurements were reported for this outcome.
Early change in tumor burden measured using the sum of longest diameters of target lesions, expressed as percent change from baseline.
| percent change | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) |
|---|---|---|
| Change in Tumor Burden | 15.0 ± 6.1 | 9.0 ± 5.5 |
Time from randomization until death or date last known alive
| months | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) |
|---|---|---|
| Overall Survival | 7.4 (4.7 to 10.3) | 8.6 (5.7 to 11.5) |
Time from randomization until disease progression/death from any cause or date last know progression-free
| months | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) |
|---|---|---|
| Progression-free Survival | 3.5 (1.8 to 3.9) | 3.5 (2.0 to 3.9) |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
| Participants | Arm I (Cetuximab and Tivantinib) | Tivantinib After Cetuximab Failure |
|---|---|---|
| Overall Response Rate of Single-agent Tivantinib After Failure of Cetuximab | — | 0 |
Non-serious adverse events, CTCAE (4.0)
| Participants | Arm I (Cetuximab and Tivantinib) | Tivantinib After Cetuximab Failure |
|---|---|---|
| Number of Participants With Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab | — | 9 |
CTCAE (4.0)
| Participants | Arm I (Cetuximab and Tivantinib) | Tivantinib After Cetuximab Failure |
|---|---|---|
| Number of Patients With Serious Adverse Events While on Single-agent Tivantinib After Failure of Cetuximab | — | 4 |
Collected over 3 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I (Cetuximab and Tivantinib) | 36/40 (90%) | 19/40 (47.5%) | 38/40 (95%) |
| Arm II (Cetuximab) | 35/38 (92.1%) | 18/38 (47.4%) | 35/38 (92.1%) |
| Single-agent Tivantinib After Failure of Cetuximab | 2/15 (13.3%) | 4/15 (26.7%) | 9/15 (60%) |
| Event | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) | Single-agent Tivantinib After Failure of Cetuximab |
|---|---|---|---|
| Lung infectionInfections and infestations | 1/40 | 1/38 | 2/15 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 5/40 | 2/38 | 1/15 |
| Neutrophil count decreasedInvestigations | 4/40 | 0/38 | 0/15 |
| DehydrationMetabolism and nutrition disorders | 2/40 | 3/38 | 0/15 |
| Febrile neutropeniaBlood and lymphatic system disorders | 3/40 | 0/38 | 1/15 |
| White blood cell decreasedInvestigations | 3/40 | 0/38 | 0/15 |
| Atrial fibrillationCardiac disorders | 0/40 | 1/38 | 1/15 |
| PainGeneral disorders | 0/40 | 1/38 | 1/15 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 1/40 | 0/38 | 1/15 |
| VomitingGastrointestinal disorders | 1/40 | 0/38 | 1/15 |
| Event | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) | Single-agent Tivantinib After Failure of Cetuximab |
|---|---|---|---|
| FatigueGeneral disorders | 21/40 | 17/38 | 3/15 |
| Rash acneiformSkin and subcutaneous tissue disorders | 20/40 | 19/38 | 1/15 |
| AnemiaBlood and lymphatic system disorders | 16/40 | 9/38 | 3/15 |
| AnorexiaMetabolism and nutrition disorders | 12/40 | 10/38 | 0/15 |
| NauseaGastrointestinal disorders | 12/40 | 10/38 | 1/15 |
| HyponatremiaMetabolism and nutrition disorders | 11/40 | 3/38 | 2/15 |
| ConstipationGastrointestinal disorders | 7/40 | 10/38 | 1/15 |
| HypomagnesemiaMetabolism and nutrition disorders | 9/40 | 10/38 | 3/15 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 10/40 | 10/38 | 2/15 |
| Lymphocyte count decreasedInvestigations | 10/40 | 4/38 | 3/15 |
| Age, Continuous(years) | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) | Total |
|---|---|---|---|
| Mean | 60.5 (37 to 90) | 63.6 (35 to 87) | 62.0 (35 to 90) |
| Sex: Female, Male(Participants) | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) | Total |
|---|---|---|---|
| Female | 6 | 6 | 12 |
| Male | 34 | 32 | 66 |
| Race (NIH/OMB)(Participants) | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 3 | 2 | 5 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 4 | 3 | 7 |
| White | 32 | 33 | 65 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(Participants) | Arm I (Cetuximab and Tivantinib) | Arm II (Cetuximab) | Total |
|---|---|---|---|
| United States | 40 | 38 | 78 |
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