CBP501, Cisplatin and Nivolumab in Advanced Refractory Tumors

NCT03113188 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CBP17-01
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter, open-label, phase 1b study of CBP501/cisplatin/nivolumab combination administered once every 21 days to patients with advanced solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Recommended dose

  Define the recommended doses (RP2D) of CBP501, cisplatin and nivolumab when administered in combination once every 21 days in patients with previously treated advanced solid tumors

  21 days

Secondary Outcomes (1)

• Hint of efficacy in pretreated pancreatic and micro-satellite stable colorectal cancer patients

  through study completion, an average of 6 month

Study Arms (1)

CBP501, CDDP, Nivolumab

EXPERIMENTAL

CBP501, Cisplatin and Nivolumab Administered Every 3 Weeks in Patients with Advanced Refractory Tumors

Drug: CBP501

Interventions

CBP501 DRUG

CBP501, CDDP plus Nivolumab

CBP501, CDDP, Nivolumab

Eligibility Criteria

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

You may qualify if:

• Signed informed consent obtained prior to initiation of any study-specific procedures and treatment;
• Previously treated, pathologically confirmed, locally advanced or metastatic solid tumors with measurable disease for which cisplatin is a reasonable treatment option, including, but not limited to, non-small cell lung, mesothelioma, head \& neck, ovarian, endometrial, breast, bladder, kidney, esophageal, gastric, colon, liver, gallbladder, cholangiocarcinoma, pancreas, soft tissue sarcoma, and osteosarcoma (for the expansion cohorts, only metastatic exocrine pancreatic cancer and microsatellite stable colorectal cancer are allowed). There is no limit on the number of prior lines of chemotherapy (including prior cisplatin), chemoradiotherapy, radiotherapy or investigational agents the patient can have received in order to be eligible, as long as cisplatin is a reasonable treatment option and all eligibility criteria are met, with the exception that a patient must not have received more than two prior lines incorporating anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint blockade.
• Patients who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint blockade therapy must have tolerated therapy with no evidence of grade 4 toxicity or an immune-related event (any grade) that required treatment discontinuation. Patients who experienced an endocrine related dysfunction are eligible, provided they are on stable hormone replacement therapy;
• Male or female patients aged ≥ 18 years at time of informed consent;
• ECOG Performance Status (PS) 0-1;
• Life expectancy \> 3 months;
• Previous anticancer treatment must be discontinued at least 3 weeks prior to the initiation of study treatment (6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, except 8 weeks for bicalutamide);
• Adequate bone marrow reserve, cardiac, liver, renal and metabolic function:
• absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
• platelet count ≥ 100 x 109/L;
• hemoglobin ≥ 9 g/dL;
• white blood cell count (WBC) ≤ upper limit of normal (ULN);
• creatinine phosphokinase isozymes CPK-MB and CPK-MM
• ≤ ULN;
• serum troponin T levels within normal limits;

You may not qualify if:

• Radiation therapy to \>30% of bone marrow prior to study entry;
• Prior chemotherapy with nitrosoureas, prior mitomycin C cumulative dose ≥ 25 mg/m2, prior bone marrow transplant, or prior intensive chemotherapy with stem cell support;
• Presence of any serious concomitant systemic disorders incompatible with the study in the opinion of the investigator (e.g., uncontrolled congestive heart failure, active infection, etc.);
• Any previous history of another malignancy (other than cured basal cell or squamous cell carcinoma of the skin or cured in-situ carcinoma) within 5 years of study entry;
• Presence of any significant central nervous system (CNS) or psychiatric disorder(s) that would hamper the patient's compliance;
• Evidence of peripheral neuropathy \> grade 1 by NCI-CTCAE version 4.03;
• Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to study entry;
• Pregnant or breast-feeding patients or any patient with child-bearing potential not using adequate contraception;
• Known HIV, HBV, or HCV infection (excluding cured HCV infection);
• Active CNS metastases; however, patients with CNS metastases will be eligible if they have been treated and are stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be off steroids;
• Who require chronic systemic steroid therapy or on any other form of immunosuppressive medication;
• Has received a live-virus vaccination within 30 days of planned treatment start;
• With known risk factors for bowel perforation, i.e., history of diverticulitis, intra-abdominal abscess, intestinal obstruction, or abdominal carcinomatosis;
• Has an active autoimmune disease or a documented history of autoimmune disease;
• Has a history pneumonitis or interstitial lung disease.

Sponsors & Collaborators

• CanBas Co. Ltd.: lead

Study Sites (3)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (6)

• Mine N, Yamamoto S, Kufe DW, Von Hoff DD, Kawabe T. Activation of Nrf2 pathways correlates with resistance of NSCLC cell lines to CBP501 in vitro. Mol Cancer Ther. 2014 Sep;13(9):2215-25. doi: 10.1158/1535-7163.MCT-13-0808. Epub 2014 Jul 22.

  PMID: 25053821 BACKGROUND

• Krug LM, Wozniak AJ, Kindler HL, Feld R, Koczywas M, Morero JL, Rodriguez CP, Ross HJ, Bauman JE, Orlov SV, Ruckdeschel JC, Mita AC, Fein L, He X, Hall R, Kawabe T, Sharma S. Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma. Lung Cancer. 2014 Sep;85(3):429-34. doi: 10.1016/j.lungcan.2014.06.008. Epub 2014 Jul 5.

  PMID: 25047675 BACKGROUND

• Matsumoto Y, Shindo Y, Takakusagi Y, Takakusagi K, Tsukuda S, Kusayanagi T, Sato H, Kawabe T, Sugawara F, Sakaguchi K. Screening of a library of T7 phage-displayed peptides identifies alphaC helix in 14-3-3 protein as a CBP501-binding site. Bioorg Med Chem. 2011 Dec 1;19(23):7049-56. doi: 10.1016/j.bmc.2011.10.004. Epub 2011 Oct 7.

  PMID: 22032894 BACKGROUND

• Mine N, Yamamoto S, Saito N, Yamazaki S, Suda C, Ishigaki M, Kufe DW, Von Hoff DD, Kawabe T. CBP501-calmodulin binding contributes to sensitizing tumor cells to cisplatin and bleomycin. Mol Cancer Ther. 2011 Oct;10(10):1929-38. doi: 10.1158/1535-7163.MCT-10-1139. Epub 2011 Aug 10.

  PMID: 21831962 BACKGROUND

• Shapiro GI, Tibes R, Gordon MS, Wong BY, Eder JP, Borad MJ, Mendelson DS, Vogelzang NJ, Bastos BR, Weiss GJ, Fernandez C, Sutherland W, Sato H, Pierceall WE, Weaver D, Slough S, Wasserman E, Kufe DW, Von Hoff D, Kawabe T, Sharma S. Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. Clin Cancer Res. 2011 May 15;17(10):3431-42. doi: 10.1158/1078-0432.CCR-10-2345. Epub 2011 Jan 10.

  PMID: 21220472 BACKGROUND

• Sha SK, Sato T, Kobayashi H, Ishigaki M, Yamamoto S, Sato H, Takada A, Nakajyo S, Mochizuki Y, Friedman JM, Cheng FC, Okura T, Kimura R, Kufe DW, Vonhoff DD, Kawabe T. Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint. Mol Cancer Ther. 2007 Jan;6(1):147-53. doi: 10.1158/1535-7163.MCT-06-0371.

  PMID: 17237275 BACKGROUND

MeSH Terms

Interventions

Cdc25C phosphatase (211-221)

Study Officials

• Geoffrey I Shapiro, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose finding cohort plus confirmatory expansion cohort

Study Record Dates

• First Submitted: April 9, 2017
• First Posted: April 13, 2017
• Study Start: October 25, 2017
• Primary Completion: February 15, 2021
• Study Completion: February 15, 2021
• Last Updated: March 10, 2021

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)