Advanced Solid Tumors
Conditions
Keywords
hepatocellular carcinoma, renal cell carcinoma, melanoma, non-small cell lung cancer, breast cancer, ovarian cancer, MiT tumors
Brief summary
This is an extension study that will allow participants to continue to receive study therapy when the original studies into which they were enrolled have reached their designated end-dates. This extension study is designed to further evaluate the safety and tolerability of tivantinib (ARQ 197) monotherapy or in combination with other drug(s) when given to participants who tolerated previous treatment well and may benefit from the continuing treatment.
Detailed description
This open label extension protocol enrolls participants who were treated in previous phase 1 (NCT01149720, NCT01517399, NCT01699061, NCT00612703, NCT00827177, and NCT00874042) and phase 2 (NCT00777309, NCT00557609, NCT00988741, NCT01395758 , and NCT01055067) tivantinib studies that have reached their designated end-dates. Participants enrolled in this extension protocol will provide further safety and tolerability information about tivantinib monotherapy or in combination with other drug(s) at the same dose(s), and same schedule(s) in which they were originally enrolled.
Interventions
DRUGTivantinib
Tivantinib 360 mg (3 x 120 mg tablets or capsules) twice daily by mouth.
DRUGAnti-Cancer Combination Therapy
Tivantinib 360 mg twice daily in combination with other anti-cancer therapy (eg, erlotinib,sorafenib, pemetrexed, docataxel, gemcitabine, irinotecan, and/or cetuximab) at the same dose and schedule in which they were administered in the original (previous) study.
Sponsors
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent to participate in clinical study of tivantinib * Male or female participants of the age defined in the original protocol they were enrolled. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤3 (or ≤2 for tivantinib-naive participants) * Adequate bone marrow function: * Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L * Hemoglobin ≥8.0 g/dL (or ≥ 9.0 g/dL for tivantinib-naïve participants) * Enrollment within 14 days of the completion of End of Treatment Visit of the original study * Participants, who participated in previous ARQ 197 studies that have reached their designated end-dates, who did not meet discontinuation criteria in their original study, and who may, in the opinion of the Investigator and the Sponsor, benefit from treatment * Women of childbearing potential must have a negative pregnancy test performed within 14 days of the start of study drug. Both men and women enrolled in this study must agree to use adequate birth control measures while on study
Exclusion criteria
* Known or suspected allergy to ARQ 197 * Substance abuse, medical, psychological or social conditions that may interfere with the participant's participation in the study or evaluation of the study results * Any condition that is unstable or which could jeopardize the safety of the participant and his/her compliance in the study * A serious uncontrolled medical disorder/condition that in the opinion of the Investigator would impair the ability of the participant to receive protocol therapy * Requirement to receive other concurrent chemotherapy (excluding combination therapy defined in original protocol), immunotherapy, radiotherapy, or any other investigational drug while on study. Palliative radiotherapy is allowed provided that: * in the opinion of the Investigator, the participant does not have progressive disease * the radiation field does not encompass a target lesion * no more than 10% of the participant's bone marrow is irradiated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Exposure to ARQ 197 in Participants Benefiting From Prior ARQ 197 Therapy | Up to 3,021 days (up to 14-Jan-2019) | The duration of ARQ 197 exposure in this study was calculated as \[(date of last dose of study drug - date of first dose of study drug) + 1\]. Results refer to duration of ARQ 197 treatment in the present study only (i.e., does not include treatment received during participation in feeder studies). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ≥1 Treatment-emergent Adverse Event (TEAE) | Up to 3021 days | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Discontinuing Treatment Due to an AE | Up to 3,021 days | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
Participant flow
Recruitment details
Adult male and female participants previously enrolled in phase 1 or phase 2 studies of tivantinib (ARQ 197) were eligible for enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Tivantinib (Monotherapy or Combination) Participants received tivantinib 360 mg twice daily by mouth as monotherapy or combination therapy. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 1 |
| Overall Study | Drug manufacturing ended | 1 |
| Overall Study | No reason provided | 1 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Progressive disease per clinician | 9 |
| Overall Study | Progressive disease per RECIST | 32 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Tivantinib (Monotherapy or Combination) |
|---|---|
| Age, Continuous | 61.6 Years STANDARD_DEVIATION 14.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 54 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 60 |
| other Total, other adverse events | 55 / 60 |
| serious Total, serious adverse events | 19 / 60 |
Outcome results
Primary
Extent of Exposure to ARQ 197 in Participants Benefiting From Prior ARQ 197 Therapy
The duration of ARQ 197 exposure in this study was calculated as \[(date of last dose of study drug - date of first dose of study drug) + 1\]. Results refer to duration of ARQ 197 treatment in the present study only (i.e., does not include treatment received during participation in feeder studies).
Time frame: Up to 3,021 days (up to 14-Jan-2019)
Population: All participants who received ≥1 dose of study drug are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tivantinib (Monotherapy or Combination) | Extent of Exposure to ARQ 197 in Participants Benefiting From Prior ARQ 197 Therapy | 125 Days |
Secondary
Number of Participants Discontinuing Treatment Due to an AE
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 3,021 days
Population: All participants who received ≥1 dose of study drug are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tivantinib (Monotherapy or Combination) | Number of Participants Discontinuing Treatment Due to an AE | 6 Participants |
Secondary
Number of Participants With ≥1 Treatment-emergent Adverse Event (TEAE)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 3021 days
Population: All participants who received ≥1 dose of study drug are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tivantinib (Monotherapy or Combination) | Number of Participants With ≥1 Treatment-emergent Adverse Event (TEAE) | 56 Participants |