Malignant Solid TumourPhase 1/2NCT01611857

Phase I/II Trial of Tivantinib With FOLFOX for the Treatment of Advanced Solid Tumors and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal Junction or Stomach

A Phase 1/2 study testing Tivantinib and FOLFOX in people with Malignant Solid Tumour and Gastroesophageal Cancer, run by SCRI Development Innovations, LLC at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is a Phase I/II trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors. In Phase I the Maximum Tolerated Dose (MTD) will be determined; in Phase II patients with first-line metastatic GE cancer will be treated at the MTD. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Malignant Solid Tumour, Gastroesophageal Cancer
What is being tested?: Tivantinib and FOLFOX
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 49 participants
Where: 9 sitesUnited States
Study dates: Jul 2012to Aug 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Life expectancy ≥12 weeks.
Karnofsky performance status ≥70%
Patients must have measurable disease per RECIST Version 1.1.
Adequate hematologic function defined as:
Absolute neutrophil count (ANC) ≥1500/μL
Hemoglobin (Hgb) ≥9 g/dL (5.6 mmol/L)

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Platelets ≥100,000/uL
Adequate liver function defined as:
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST <2.5 x the institutional upper limit of normal (ULN) or ≤5.0 x the institutional ULN in patients with liver metastases.
Total bilirubin within normal limits (WNL) (or ≤1.5 x the institutional ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin within normal limits in patients with well documented Gilbert Syndrome).
Serum creatinine <1.5 X ULN or calculated 24-hour creatinine clearance >40 mL/min.
Patients who are on coumadin should have an international normalized ratio (INR) value within the therapeutic range (i.e., 2 to 3 x ULN). Patients who are on stable, chronic doses of coumadin are eligible.
PHASE I ONLY
•Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard therapy would include FOLFOX or for which standard curative or palliative measures do not exist or are no longer effective.
PHASE II ONLY
Histologic documentation of adenocarcinoma of the esophagus, GE junction, or stomach.
Metastatic GE cancer as documented by radiologic study or surgical evidence of metastatic disease.
No prior chemotherapy for metastatic disease. Previous combined modality therapy for locally advanced disease is allowed if completed ≥6 months prior to recurrence (acceptable chemotherapy drugs include 5-FU, capecitabine, cisplatin, carboplatin, paclitaxel, oxaliplatin, and docetaxel).
Prior radiation therapy is allowed. At least 4 weeks must have elapsed from completion of the radiation therapy and all signs of toxicity must have resolved.
Prior adjuvant chemotherapy is allowed if completed ≥6 months prior to the documentation of metastatic disease.

Who cannot join

Patients with known central nervous system (CNS) metastases may be enrolled, provided the metastases have undergone treatment, the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases.
Patients with poorly controlled or clinically significant atherosclerotic vascular disease including New York Heart Association Grade 3 or greater congestive heart failure; unstable angina ; myocardial infarction, cardiovascular accident, transient ischemic accidents, angioplasty, cardiac or vascular stenting in the past 6 months; or ventricular arrhythmia requiring medication. Patients with previously diagnosed symptomatic bradycardia will be ineligible.
Medical history of prolonged QT syndrome (>450 ms).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements.
History of hypersensitivity to active or inactive excipients of any component of treatment (5-FU, leucovorin, oxaliplatin, or Tivantinib), or known dipyrimidine dehydrogenase deficiency.
Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).

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Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) ≤6 months prior to Day 1 of treatment.
Any known positive test for human immunodeficiency virus, hepatitis C virus or acute or chronic hepatitis B infection.
Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
Use of any non-approved or investigational agent ≤28 days or 5 half-lives prior to administration of the first dose of study drug, whichever is shorter.
Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g. active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
Inability to swallow whole capsules.
PHASE I ONLY
•Patients who have had radiation therapy, hormonal therapy, biologic therapy, investigational agents, or chemotherapy for cancer within 28 days or 5 half-lives of the chemotherapy or biologic/targeted agents, whichever is shorter, prior to Day 1 of the study.
PHASE II ONLY
•Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a disease free survival ≥5 years.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

Tennessee Oncology - Chattanooga
Chattanooga, Tennessee, 37404
South Carolina Oncology Associates
Columbia, South Carolina, 29210
Florida Cancer Specialists-South
Fort Myers, Florida, 33916
Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
Tennessee Oncology, PLLC
Nashville, Tennessee, 37023
Yale University School of Medicine
New Haven, Connecticut, 06520
Oklahoma University
Oklahoma City, Oklahoma, 73104
Florida Cancer Specialists-Sarasota
Sarasota, Florida, 34232
Florida Cancer Specialists-North
St. Petersburg, Florida, 33705

Other trials in United States

About this study

Official title: A Phase I/II Trial of the c-Met Inhibitor, Tivantinib, in Combination With FOLFOX for the Treatment of Patients With Advanced Solid Tumors (Phase I) and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal (GE) Junction, or Stomach (Phase II)

Read the detailed description

This is a Phase I, open-label, non-randomized, dose-escalation study with a Phase II portion planned upon reaching the Maximum Tolerated Dose or recommended Phase II dose (RP2D). Phase I: The first cycle of the Phase I portion of the trial will be considered the Dose Limiting Toxicity evaluation period. Patients with advanced solid tumors will be treated with Tivantinib on Days 1 to 14 and with FOLFOX on Day 1. Following evaluation of the Dose Limiting Toxicities, doses will be escalated/reduced according to the protocol with 3 to 6 patients treated per dose level until the Maximum Tolerated Dose is determined.

Conditions: Malignant Solid Tumour, Gastroesophageal Cancer
Being tested: Tivantinib, FOLFOX
Keywords: Advanced solid tumors, First-Line Metastatic GE cancer, c-Met Inhibitor, Tivantinib, FOLFOX

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TivantinibDrug
Also called ARQ 197
Patients with advanced solid tumors will be treated with oral Tivantinib (120, 240, or 360 mg BID) daily for 14 days in cycles of 14 days.
FOLFOXDrug
Also called 5-FU, Leucovorin, Oxaliplatin, Levoleucovorin
The FOLFOX treatment regimen is started on Day 1 of each cycle and consists of 5-Fluorouracil (5-FU) 400 mg/m^2, 5-FU continuous IV 2400 mg/m^2 over 46 hours, leucovorin 400 mg/m^2 IV, and oxaliplatin 85 mg/m^2.

Study groups in NCT01611857
Study group	Role	What they receive
Maximum Tolerated Dose	Experimental	Phase I trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors followed by a Phase II portion for patients with first-line metastatic GE cancer. Receives: Drug: Tivantinib; Drug: FOLFOX

What is being measured

The primary outcome is the main question the study is designed to answer.

The Incidence of Dose Limiting Toxicities (DLT) in Phase I Dose Escalation
Using a standard 3+3 design participants were enrolled in dose-escalating cohorts to determine the maximum tolerated dose (MTD) of tivantinib when given with FOLFOX (5-FU 400 mg/m^2, continuous IV 5-FU 2400 mg/m^2 over 46 hours, leucovorin 400 mg/m^2 IV, and oxaliplatin 85 mg/m^2). MTD is defined as the highest dose level at which no more than 1 of 6 patients experiences a DLT, assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.
Measured: 14 Days (1 cycle)

Secondary outcomes (3)

Progression Free Survival in Phase II Dose Expansion
Defined as the time from first treatment until objective tumor progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: every 8 weeks until treatment discontinuation, projected 18 months and then every 3 months thereafter up to 5 years from start of treatment.
Overall Survival in Phase II Dose Expansion
Defined as the time from first treatment until death from any cause.
Measured: every 8 weeks until treatment discontinuation, an expected average of 18 months, then every 12 weeks thereafter up to 5 years from start of treatment.
Time to Progression in Phase II Dose Expansion
Defined as the time from first treatment until objective tumor progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: every 8 weeks until progressive disease, expected 18 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2012Aug 2015

First posted5 Jun 2012 (estimated)
Study startJul 2012
Primary completionJul 2015
Study completionAug 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Malignant Solid TumourStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01611857
Sponsor's protocol ID: SCRI GI 157
Status last verified: Oct 2016
First submitted: 1 Jun 2012
Last updated: 23 Nov 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Malignant Solid Tumour trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Trial of the c-Met Inhibitor, Tivantinib, in Combination With FOLFOX for the Treatment of Patients With Advanced Solid Tumors (Phase I) and Previously Untreated Metastatic Adenocarcinoma of the Distal Esophagus, Gastroesophageal (GE) Junction, or Stomach (Phase II)
ClinicalTrials.gov ID: NCT01611857
Acronym / sponsor ID: SCRI GI 157
Conditions: Malignant Solid Tumour, Gastroesophageal Cancer
Keywords: Advanced solid tumors, First-Line Metastatic GE cancer, c-Met Inhibitor, Tivantinib, FOLFOX
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 49 participants (actual)
Lead sponsor: SCRI Development Innovations, LLCUniversity, hospital or other
Collaborators: Daiichi Sankyo
Study start: Jul 2012
Primary completion: Jul 2015 (actual)
Study completion: Aug 2015 (actual)
First posted: 5 Jun 2012 (estimated)
Results: Posted 23 Nov 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Maximum Tolerated Dose	Experimental	Drug: Tivantinib, Drug: FOLFOXPhase I trial of Tivantinib plus FOLFOX for the treatment of patients with advanced solid tumors followed by a Phase II portion for patients with first-line metastatic GE cancer.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (20 listed)

Life expectancy ≥12 weeks.
Karnofsky performance status ≥70%
Patients must have measurable disease per RECIST Version 1.1.
Adequate hematologic function defined as:
Absolute neutrophil count (ANC) ≥1500/μL

Key exclusion criteria (17 listed)

Patients with known central nervous system (CNS) metastases may be enrolled, provided the metastases have undergone treatment, the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases.
Patients with poorly controlled or clinically significant atherosclerotic vascular disease including New York Heart Association Grade 3 or greater congestive heart failure; unstable angina ; myocardial infarction, cardiovascular accident, transient ischemic accidents, angioplasty, cardiac or vascular stenting in the past 6 months; or ventricular arrhythmia requiring medication. Patients with previously diagnosed symptomatic bradycardia will be ineligible.
Medical history of prolonged QT syndrome (>450 ms).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements.
History of hypersensitivity to active or inactive excipients of any component of treatment (5-FU, leucovorin, oxaliplatin, or Tivantinib), or known dipyrimidine dehydrogenase deficiency.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TivantinibAlso: ARQ 197Patients with advanced solid tumors will be treated with oral Tivantinib (120, 240, or 360 mg BID) daily for 14 days in cycles of 14 days.	Drug	Maximum Tolerated Dose
FOLFOXAlso: 5-FU, Leucovorin, Oxaliplatin, LevoleucovorinThe FOLFOX treatment regimen is started on Day 1 of each cycle and consists of 5-Fluorouracil (5-FU) 400 mg/m^2, 5-FU continuous IV 2400 mg/m^2 over 46 hours, leucovorin 400 mg/m^2 IV, and oxaliplatin 85 mg/m^2.	Drug	Maximum Tolerated Dose

Primary outcome

The Incidence of Dose Limiting Toxicities (DLT) in Phase I Dose Escalation
Time frame: 14 Days (1 cycle)
Using a standard 3+3 design participants were enrolled in dose-escalating cohorts to determine the maximum tolerated dose (MTD) of tivantinib when given with FOLFOX (5-FU 400 mg/m^2, continuous IV 5-FU 2400 mg/m^2 over 46 hours, leucovorin 400 mg/m^2 IV, and oxaliplatin 85 mg/m^2). MTD is defined as the highest dose level at which no more than 1 of 6 patients experiences a DLT, assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.

3 secondary outcomes

Progression Free Survival in Phase II Dose Expansion
Time frame: every 8 weeks until treatment discontinuation, projected 18 months and then every 3 months thereafter up to 5 years from start of treatment.
Overall Survival in Phase II Dose Expansion
Time frame: every 8 weeks until treatment discontinuation, an expected average of 18 months, then every 12 weeks thereafter up to 5 years from start of treatment.
Time to Progression in Phase II Dose Expansion
Time frame: every 8 weeks until progressive disease, expected 18 months.

Results and safety

Results posted to the registry on 23 Nov 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tivantinib + FOLFOX Dose Escalation	15	15
Tivantinib + FOLFOX Dose Expansion	34	32

Primary outcome: The Incidence of Dose Limiting Toxicities (DLT) in Phase I Dose Escalation

Time frame: 14 Days (1 cycle). Number. Unit: participants

Measure	Tivantinib 120 mg (PO BID) + FOLFOX n = 3	Tivantinib 240 mg (PO BID) + FOLFOX n = 3	Tivantinib 360 mg (PO BID) + FOLFOX n = 6
Value	0	0	1

Population analysed: Patients were assessed for DLT if they received at least 85% of the scheduled doses of study drugs in cycle 1. In the Tivantinib 120 mg cohort two participants were replaced due to missed drug. In the Tivantinib 360 mg cohort one patient was replaced due to an allergic reaction to oxaliplatin.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Collected from day of first dose to 30 days after last dose of study medication up to 18 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tivantinib+FOLFOX Dose Escalation	6 of 15 (40%)	14 of 15 (93.3%)	Not reported
Tivantinib+FOLFOX Dose Expansion	17 of 32 (53.1%)	31 of 32 (96.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Malignant Solid Tumour

RecruitingObservational study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Johanna C Bendell, M.D. study chair

SCRI Development Innovations, LLC

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tivantinib and FOLFOX in people with Malignant Solid Tumour and Gastroesophageal Cancer, run by SCRI Development Innovations, LLC at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Incidence of Dose Limiting Toxicities (DLT) in Phase I Dose Escalation (time frame: 14 Days (1 cycle)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01611857.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2016.