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CholangiocarcinomaPhase 1/2NCT02128282

Study of CX-4945 in Combination With Gemcitabine and Cisplatin for Frontline Treatment of Cholangiocarcinoma

A Phase 1/2 study testing CX-4945, Cisplatin and Gemcitabine in people with Cholangiocarcinoma, run by Senhwa Biosciences, Inc. at 16 sites in 3 countries.

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 considers the safety and tolerability of increasing doses of CX-4945 in combination with gemcitabine plus cisplatin to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D), followed by a randomized study that compares antitumor activity in cholangiocarcinoma patients receiving… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cholangiocarcinoma
What is being tested?
CX-4945, Cisplatin and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
127 participants
Where
16 sitesin 3 countries
Study dates
Jun 2014to 5 Aug 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Presence of an unresectable hepatobiliary mass or metastatic disease (consistent with cholangiocarcinoma, as evidenced by histology or cytology (augmented by fluorescence in situ hybridization (FISH) where appropriate), for which treatment with gemcitabine plus cisplatin is intended. Intrahepatic and extrahepatic cholangiocarcinoma patients may be enrolled.
  • For patients enrolled in the Dose Escalation Phase, one or more tumors measurable on radiograph or CT scan, or evaluable disease defined as non-measurable lesions per RECIST v. 1.1 (e.g., malignant ascites). All patients enrolled to the Randomized Study Phase must have measurable disease only.
  • Laboratory data as specified below:
  • Hematology: Absolute neutrophil count (ANC) >1,500 cells/mm3, platelet count >100,000 cells/ mm.cu. and hemoglobin > 9 g/dL
  • Hepatic: bilirubin <1.5 X Upper Limit of Normal (ULN); alkaline phosphatase (ALP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5.0 X ULN
  • Renal: serum creatinine within normal limits (WNL), defined as within 25% of the institution's stated reference range, or a calculated creatinine clearance >45 mL/min/1.73 m. sq. for patients with abnormal, increased, creatinine levels.
  • Coagulation: International Normalized Ratio (INR) < 1.5 times normal, activated Partial Thromboplastin Time (aPTT) < 1.5 times normal. Patients receiving therapeutic doses of anticoagulant therapy may be considered eligible for the trial if INR and aPTT are within the acceptable therapeutic limits for the institution.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1.

Who cannot join

  • A history of prior systemic treatment with gemcitabine or cisplatin. At least six months must have elapsed if gemcitabine or cisplatin was administered in an adjuvant treatment setting. Patients enrolled in the Expansion Cohort, Exploratory Cohorts, and the Randomized Phase must not have received prior systemic chemotherapies, including chemoradiation therapy for cholangiocarcinoma.
  • Seizure disorders requiring anticonvulsant therapy.
  • Known brain metastases (unless previously treated and well controlled for a period of at least 3 months).
  • Major surgery other than diagnostic surgery, within 4 weeks prior to the first dose of test drug, minor surgery including diagnostic surgery within 2 weeks (14 days) excluding central IV port placements and needle aspirate/core biopsies. Radio frequency ablation or transcatheter arterial chemoembolization within 6 weeks prior to the first dose of test drug.
  • Treatment with radiation therapy or surgery within one month prior to study entry.
  • Treatment with chemotherapy or investigational drugs within 21 days prior to the screening visit. Acute toxicities from prior therapy must have resolved to Grade ≤ 1 above baseline.
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  • Patients with a history of another malignancy within 3 years of the baseline visit. (Patients with cutaneous carcinomas or in-situ carcinomas will be considered for study entry on a case-by-case basis).
  • Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure).
  • Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis which would not permit the patient to be managed according to the protocol.
  • Difficulty with swallowing or an active malabsorption syndrome.
  • Chronic diarrhea (excess of 2-3 stools/day above normal frequency).
  • Gastrointestinal diseases including ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
  • History of gastric or small bowel surgery involving any extent of gastric or small bowel resection.
  • Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis.

Trial locations and contacts

16 sites in 3 countries.

16 sites in 3 countries

United States6 sites
  • University of Colorado- Denver

    Aurora, Colorado, 80045

  • Texas Oncology - Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Mayo Clinic

    Jacksonville, Florida, 32224

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic

    Scottsdale, Arizona, 85259-5499

  • Texas Oncology-Tyler

    Tyler, Texas, 75702

Other trials in United States

Taiwan6 sites
  • Chang-Gung Memorial Hospital - Kaohsiung Branch

    Kaohsiung City

  • China Medical University Hospital

    Taichung

  • National Cheng Kung University Hospitals

    Tainan

  • National Taiwan University Hospital

    Taipei

  • Taipei Veterans General Hospital

    Taipei

  • Chang-Gung Memorial Hospital - Linkou Branch

    Taoyuan City

Other trials in Taiwan

South Korea4 sites
  • Asan Medical Center

    Seoul, Songpa-gu, 138-736

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Severance Hospital, Yonsei University Health System

    Seoul

Other trials in South Korea

About this study

Official title: A Phase I/II Study of CX-4945 in Combination With Gemcitabine and Cisplatin in the Frontline Treatment of Patients With Cholangiocarcinoma

This study considers the safety and tolerability of increasing doses of CX-4945 in combination with gemcitabine plus cisplatin to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D), followed by a randomized study that compares antitumor activity in cholangiocarcinoma patients receiving the standard of care gemcitabine plus cisplatin versus CX-4945 at the combination RP2D with gemcitabine plus cisplatin.

Read the detailed description

Protein kinase CK2 is a constitutively active serine/threonine kinase with a long history as a pro-survival, anti-apoptotic kinase. Given the wide spread overexpression of CK2 in multiple cancers and its role in multiple non-oncogenic processes required to sustain the cancer phenotype, a selective inhibitor of CK2 is an attractive targeted approach to treating cancer.

CX-4945 is a tetracyclic, small molecule carboxylate acid salt that exhibits potent and highly selective inhibition of CK2. Protein kinase CK2 is also known to play an important role in the DNA damage repair mechanisms of cancer cells, and this study of CX-4945 in combination with gemcitabine plus cisplatin will determine if inhibition of CK2, in conjunction with the use of chemotherapy drugs, will result in improved clinical outcomes for patients with non-resectable cholangiocarcinoma.

Being tested
CX-4945, Cisplatin, Gemcitabine
Keywords
Cholangiocarcinoma, Bile duct cancer, Biliary tract cancer
Medical subject headings
Cholangiocarcinoma, Bile Duct Neoplasms, Biliary Tract Neoplasms

What participants receive

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

  • CX-4945Drug

    API powder-in-capsule in 200 mg strength.

  • CisplatinDrug

    Also called Platinol

    25 mg/m.sq. administered by IV infusion on Days 1 and 8 of a 21-day cycle.

  • GemcitabineDrug

    Also called Gemzar

    1,000 mg/m.sq. administered by IV infusion on Days 1 and 8 of a 21-day cycle.

Study groups in NCT02128282
Study groupRoleWhat they receive
Escalation CX-4945 plus Cis/GemExperimentalCX-4945 capsules at the combination MTD on Days 0, 1 and 2, and Days 7, 8 and 9. PLUS Cisplatin 25 mg/m.sq. by IV infusion on Days 1 and 8. PLUS Gemcitabine 1,000 mg/m.sq. by IV infusion on Days 1 and 8. On a 21-day cycle.
Receives: Drug: CX-4945; Drug: Cisplatin; Drug: Gemcitabine
Cisplatin plus GemcitabineActive comparatorCisplatin 25 mg/m.sq. by IV infusion on Days 1 and 8. PLUS Gemcitabine 1,000 mg/m.sq. by IV infusion on Days 1 and 8. On a 21-day cycle.
Receives: Drug: Cisplatin; Drug: Gemcitabine
10-day CX-4945 plus Cis/GemExperimentalCX-4945 capsules at 1000mg/BID, 10-day continuous dosing (Day 0 through Day 9). PLUS Cisplatin 25 mg/m.sq. by IV infusion on Days 1 and 8. PLUS Gemcitabine 1,000 mg/m.sq. by IV infusion on Days 1 and 8. On a 21-day cycle.
Receives: Drug: CX-4945; Drug: Cisplatin; Drug: Gemcitabine
21-day CX-4945 plus Cis/GemExperimentalCX-4945 capsules at 1000mg/BID, 21-day continuous dosing PLUS Cisplatin 25 mg/m.sq. by IV infusion on Days 1 and 8. PLUS Gemcitabine 1,000 mg/m.sq. by IV infusion on Days 1 and 8. On a 21-day cycle.
Receives: Drug: CX-4945; Drug: Cisplatin; Drug: Gemcitabine

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of CX-4945 when used in combination with gemcitabine plus cisplatin. (Phase 1)

    The Maximum Tolerated Dose of CX-4945 will be determined from safety observations during the first cycle, as the CX-4945 dose is escalated in cohorts of three patients in combination with standard gemcitabine plus cisplatin.

    Measured: Cycle 1, 1 Full cycle up to twenty-one (21) days

  2. Comparison of the Progression-free survival (PFS) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 (Phase 2)

    Tumor measurements will be compared to baseline every six weeks, and the PFS will be determined using RECIST v. 1.1.

    Measured: From date of randomization to date of progression or death from any cause up to 52 weeks.

  3. Recommended Phase II dose (RP2D) and schedule of CX-4945 in combination with gemcitabine plus cisplatin (Phase I)

    The recommended Phase II dose and schedule of CX-4945 will be determined from safety observations during the first cycle, as the CX-4945 dose is administered 1000mg BID in 10-day continuous or 21-day continuous cohorts in combination with standard gemcitabine plus cisplatin.

    Measured: Cycle 1, 1 Full cycle up to twenty-one (21) days

Secondary outcomes (3)
  1. Comparison of the Overall Response Rate (ORR) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1

    Tumor measurements will be compared to baseline, and the ORR will be determined using RECIST v. 1.1

    Measured: From date of randomization to date of progression or death from any cause up to 52 weeks.

  2. Comparison of the number of patient who transition to surgical resection

    The number of patients in the chemotherapy arm versus CX-4945 plus chemotherapy arm who transition to surgical resection will be compared.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

  3. Comparison of the Overall Survival (OS) between the test and the control arms

    Time to event is observed during treatment and followed up every 3 months after patient withdraw from treatment.

    Measured: From date of randomization to date of death from any cause up to 52 weeks.

Timeline

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

  1. First posted1 May 2014 (estimated)
  2. Study startJun 2014
  3. Primary completion6 Nov 2020
  4. Study completion5 Aug 2021

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
127 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02128282
Sponsor's protocol ID
S4-13-001
Status last verified
Oct 2021
First submitted
28 Apr 2014
Last updated
22 Oct 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CX-4945, Cisplatin and Gemcitabine in people with Cholangiocarcinoma, run by Senhwa Biosciences, Inc. at 16 sites in 3 countries.

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 8 inclusion and 14 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 22 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Taiwan, South Korea. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum Tolerated Dose (MTD) of CX-4945 when used in combination with gemcitabine plus cisplatin. (Phase 1) (time frame: Cycle 1, 1 Full cycle up to twenty-one (21) days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 22 Oct 2021.

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