Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma

NCT04088188 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: ACCRU-ICRN-1701NCI-2019-05811P30CA015083
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 7

Brief Summary

This phase I trial studies the side effects and best dose of gemcitabine and cisplatin when given together with ivosidenib or pemigatinib in treating patients with cholangiocarcinoma that cannot be removed with surgery (unresectable) or has spread to other places in the body (metastatic). Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ivosidenib and pemigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and cisplatin with ivosidenib or pemigatinib may work better in treating patients with cholangiocarcinoma compared to gemcitabine and cisplatin alone.

Conditions

Advanced Cholangiocarcinoma; Metastatic Cholangiocarcinoma; Unresectable Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Significant Toxicities

  A significant toxicity is defined as a Dose Limiting Toxicity that is possibly, probably, or definitely related to treatment. DLTs will be evaluated starting in the first cycle of combination treatment and up to 3 weeks of combination treatment. Toxicities will be assessed using the CTEP Active Version of the CTCAE. All patients meeting the eligibility criteria who have signed a consent form and have begun combination treatment will be considered evaluable for significant toxicity. Patients, who do not experience a DLT but withdraw from protocol therapy prior to 3 weeks, will not be evaluable for the primary endpoint. Incidence of significant toxicity at 3 weeks will be estimated separately by arm and will be defined as the number of patients with significant toxicity within 3 weeks of combination treatment divided by the total number of evaluable patients.

  3 weeks

Secondary Outcomes (5)

• Overall Survival

  27 months

• Progression Free Survival

  24 months

• Number of Patients Experiencing Adverse Events

  16 months

• Number of Participants Experiencing Toxicities

  16 months

• Best Response

  15 months

Study Arms (2)

Arm A (ivosidenib, cisplatin, gemcitabine)

EXPERIMENTAL

Patients receive ivosidenib PO on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Drug: Gemcitabine; Drug: Ivosidenib

Arm B (pemigatinib, cisplatin, gemcitabine)

EXPERIMENTAL

Patients receive pemigatinib PO on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemigatinib

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (ivosidenib, cisplatin, gemcitabine); Arm B (pemigatinib, cisplatin, gemcitabine)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Arm A (ivosidenib, cisplatin, gemcitabine); Arm B (pemigatinib, cisplatin, gemcitabine)

Ivosidenib DRUG

Given PO

Also known as: AG-120, Tibsovo

Arm A (ivosidenib, cisplatin, gemcitabine)

Pemigatinib DRUG

Given PO

Also known as: INCB054828, Pemazyre

Arm B (pemigatinib, cisplatin, gemcitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathological diagnosis (fresh) or banked tumor biopsy sample collected within the last 3 years from the registration date consistent with nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation, or ablative therapies
• Documented disease without any evidence of progression following at least 3 cycles of standard-of-care chemotherapy including gemcitabine and cisplatin as part of first-line systemic therapy; NOTE: Only patients receiving standard-of-care chemotherapy including gemcitabine and cisplatin as first-line therapy for unresectable or metastatic cholangiocarcinoma will be permitted to enroll in this trial. Prior systemic adjuvant chemotherapy is allowed as long as there was no evidence of recurrence within 6 months of completing the adjuvant therapy
• Molecular testing result from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (using fresh tumor biopsy or most recent banked tumor tissue available) confirming that the tumor tissue has at least one of the following:
• IDH1 gene mutation (R132C/L/G/H/S mutation)
• FGFR2 gene alteration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Life expectancy \>= 3 months
• At least one evaluable and measurable lesion by RECIST criteria prior to beginning chemotherapy with gemcitabine and cisplatin
• NOTE: Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, hepatic arterial infusion, or radiation therapy) are eligible provided measurable disease falls outside of the treatment
• Recovered from toxicities associated with prior anticancer therapy to baseline unless stabilized under medical management
• Absolute neutrophil count \>= 1,500/mm\^3 (obtained =\< 21 days prior to registration)
• Platelet count \>= 100,000/mm\^3 (obtained =\< 21 days prior to registration)
• Hemoglobin \>= 8 g/dL (obtained =\< 21 days prior to registration)
• Serum total bilirubin =\< 2.0 x upper limit of normal (ULN), unless considered due to Gilbert's disease. If Gilbert's disease or disease involving liver, serum total bilirubin =\< 2.5 x ULN (obtained =\< 21 days prior to registration)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN or =\< 5.0 x ULN in the presence of liver metastases (obtained =\< 21 days prior to registration)

You may not qualify if:

• Prior therapy with either an IDH inhibitor or selective FGFR inhibitor
• IDH inhibitors: ivosidenib, FT-2012, etc.
• FGFR inhibitors: pemigatinib, BGJ-398, TAS-120, ARQ 087, or derazantinib, etc.
• Progressive disease as best response on current standard-of-care chemotherapy including gemcitabine and cisplatin
• Known toxicity to standard-of-care chemotherapy including gemcitabine and cisplatin requiring cessation of this therapy
• Received radiotherapy to metastatic sites of disease =\< 2 weeks prior to registration
• Underwent hepatic radiation, chemoembolization, or radiofrequency ablation =\< 4 weeks prior to registration
• Known symptomatic brain metastases requiring steroids
• NOTE: Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and have radiographically stable disease for at least 3 months prior to registration
• NOTE: Up to 10 mg per day of prednisone equivalent will be allowed
• Other active malignancy =\< 5 years prior to registration. EXCEPTIONS:
• Non- melanoma skin cancer unless stage 1a or carcinoma-in-situ of the cervix
• Breast cancer with ongoing hormone therapy being administered as adjuvant therapy
• NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment
• Major surgery =\< 4 weeks prior to registration or have not recovered from post-surgery toxicities

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (7)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Spartanburg Regional Medical Center

Forest City, North Carolina, 28043, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Aurora Cancer Care-Milwaukee West

Wauwatosa, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine; ivosidenib; pemigatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Shubham Pant
• Organization: MD Anderson

spant@mdanderson.org

832-803-5306

Study Officials

• Shubham Pant

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 12, 2019
• Study Start: January 25, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 6, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Locations

US (7)