Study of CBP501/Cisplatin/Nivolumab Combinations in Advanced Pancreatic Cancer

Recruiting at 37 trial locations

Overseen By Takumi Kawabe, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CanBas Co. Ltd.

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: CNS disorders, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 12-30 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests combinations of three drugs to treat advanced pancreatic cancer. It targets patients with advanced cancer and specific blood cell counts. The drugs work by killing cancer cells and helping the immune system fight the cancer. Gemcitabine has been a cornerstone in the treatment of advanced pancreatic cancer, often used in combination with other drugs to improve efficacy.

Will I have to stop taking my current medications?

The trial requires that previous anticancer treatments be stopped at least 3 weeks before starting the study treatment, with specific longer periods for certain drugs like mitomycin C and anti-androgen therapies. However, the protocol does not specify if you need to stop other current medications, so it's best to discuss this with the study team.

What evidence supports the effectiveness of the drug CBP501, Cisplatin, and Nivolumab?

Cisplatin, a component of the treatment, has shown strong effectiveness against various cancers, including testicular, bladder, and head and neck cancers. It works by forming DNA crosslinks that prevent cancer cells from dividing. Additionally, cisplatin analogs like carboplatin have been developed to reduce toxicity while maintaining effectiveness. ^{1 2 3 4 5}

What safety data exists for treatments like CBP501 and Cisplatin?

Cisplatin, also known as CDDP, has been used in cancer treatment since 1972 and is known to cause side effects like nausea, vomiting, kidney problems, and hearing loss. CBP501, when used with Cisplatin, commonly causes infusion-related skin reactions. Safety measures can help reduce kidney damage from Cisplatin. ^{3 6 7 8 9}

What makes the drug combination of CBP501, Cisplatin, and Nivolumab unique?

This drug combination is unique because CBP501 acts as a G2 checkpoint abrogator, potentially enhancing the effectiveness of cisplatin by disrupting cancer cell repair mechanisms, while Nivolumab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells. This multi-faceted approach may offer a novel strategy for treating advanced solid tumors. ^{3 10 11 12 13}

Eligibility Criteria

Inclusion Criteria

Adequate bone marrow reserve, cardiac, liver, renal and metabolic function: white blood cell count (WBC) <10,000/mm3; absolute neutrophil count (ANC) ≥ 1,500/mm3; platelet count ≥ 100,000/mm3; hemoglobin ≥ 9 g/dL; creatinine phosphokinase isozymes CPK-MB and CPK-MM ≤ upper limit of normal (ULN); serum troponin T levels within normal limits; bilirubin ≤ 1.5 x ULN; alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present); INR ≤ 1.5 x ULN; serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min (by Cockcroft & Gault formula or alternate calculation by 24hr urine collection). Patients with serum creatinine ≤ ULN and clearance between 45 to 59 mL/min should reduce cisplatin dose by 50%; serum potassium ≥ 3.0 and ≤ 5.5 mmol/L; serum calcium ≥ 8.0 and ≤ 11.5 mg/dL (≥ 2.0 and ≤ 2.9 mmol/L); serum magnesium ≥ 1.2 and ≤ 3.0 mg/dL (≥ 0.5 and ≤ 1.23 mmol/L); Female patients of child-bearing potential must have a negative serum pregnancy test and use at least one form of contraception as approved by the investigator for 4 weeks prior to initiating study treatment and for 14 months after the last dose of study drug . For the purposes of this study, child-bearing potential is defined as "all female patients unless they are post-menopausal for at least 3 years or surgically sterile; Male patients must use a form of barrier contraception approved by the investigator during the study and for 14 months after the last dose of study drug.

Signed informed consent obtained prior to initiation of any study-specific procedures and treatment;

Patients with pathologically confirmed stage IV exocrine pancreatic cancer who have received at least two lines of systemic therapy for metastatic disease. Up to 10 of prior lines of systemic therapy (including prior cisplatin), chemoradiotherapy, radiotherapy or investigational agents the patient has received are allowed in order to be eligible, as long as 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.

Exclusion Criteria

Has received a live-virus vaccination within 30 days of planned treatment start;

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;

Radiation therapy to >30% of bone marrow prior to study entry;

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive combinations of CBP501, cisplatin, and nivolumab administered once every 21 days for up to 4 cycles, with potential for 6 additional cycles of single-agent nivolumab if progression-free

12-30 weeks

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with tumor assessments every 8 weeks and every 3 months post-treatment until disease progression

1 year

Every 8 weeks (in-person), every 3 months (in-person)

Treatment Details

Interventions

• CBP501
• Cisplatin
• Nivolumab

Participant Groups

Group I: Arm 4: Cisplatin + Nivolumab Experimental Treatment 2 Interventions

Cisplatin 60mg/m2 will be administered as infusion and then Nivolumab 240mg will be administered.

Group II: Arm 3: CBP501 (25) + Cisplatin Experimental Treatment 2 Interventions

CBP501 25mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously.

Group III: Arm 2: CBP501 (16) + Cisplatin + Nivolumab Experimental Treatment 3 Interventions

CBP501 16mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously. Nivolumab 240mg will be administered following the completion of CBP501 and cisplatin infusions.

Group IV: Arm 1: CBP501 (25) + Cisplatin + Nivolumab Experimental Treatment 3 Interventions

CBP501 25mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously. Nivolumab 240mg will be administered following the completion of CBP501 and cisplatin infusions.

Who Is Running the Clinical Trial?

CanBas Co. Ltd.

Lead Sponsor

Trials

5

Recruited

400+

Findings from Research

Cis-diamminedichloroplatinum(II) (cis-DDP) is a highly effective antineoplastic agent, particularly against non-seminomatous testicular cancer, bladder cancer, and head and neck tumors, with mild myelosuppression allowing for combination therapies.

Despite its potential for nephrotoxicity, this side effect can be managed through forced diuresis, making cis-DDP a viable option for combination chemotherapy in treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diamminedichloroplatinum(II). A new antineoplastic agent derived from the group of heavy metal complexes (author's transl)]. Osieka, R., Schmidt, CG.[2019]

Cisplatin is an effective antitumor agent but has significant toxicities that limit its use, prompting the development of safer analogs like carboplatin (CBDCA) and iproplatin (CHIP).

Preclinical and early clinical trials indicate that both carboplatin and iproplatin retain antitumor activity against tumors responsive to cisplatin, suggesting they may offer improved safety profiles for treating certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A strategy for the development of two clinically active cisplatin analogs: CBDCA and CHIP. Foster, BJ., Harding, BJ., Wolpert-DeFilippes, MK., et al.[2019]

Cisplatin (CDDP) has been a key treatment for various cancers since 1972, but its use is limited by significant toxicities, particularly renal impairment.

Carboplatin (CBDCA), a second-generation analogue of cisplatin, has shown reduced renal toxicity and is effective against advanced cancers, although it can cause myelosuppression, particularly affecting platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. Ariyoshi, Y., Ota, K.[2013]

A phase II trial of cisdiammino-dichloro platinum (CDDP) showed significant effectiveness against testis embryonic carcinoma, ovarian carcinoma, and epidermoid cancers, particularly in head and neck and cervical cancers.

While CDDP demonstrates strong anti-cancer activity, it is associated with notable toxicity primarily affecting the digestive and renal systems, leading to its use in combination therapies for the indicated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. Hayat, M., Bayssas, M., Brulé, G., et al.[2013]

In a Phase I study involving 40 patients with urologic and gynecologic cancers, cis-diamminedichloroplatinum(II) (CIS-DDP) was found to have manageable side effects, primarily nausea, vomiting, and anorexia, which resolved quickly after stopping the treatment.

The study indicated low levels of hematopoietic and renal toxicities, with no reported cases of hearing disturbances or tinnitus, suggesting a favorable safety profile for CIS-DDP at doses of 50 mg/m2 for single administration and 20 mg/m2/day for five consecutive days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

Cis-diamminedichloroplatinum (DDP) has shown strong efficacy against germinal tumors of the testis and promising results in various epithelial cancers, including ovarian and bladder cancers, based on renewed clinical interest and research.

Recent advancements, such as induced diuresis to reduce nephrotoxicity and the identification of safer dosing strategies, suggest that DDP could have a significant future role in cancer treatment, although further investigation into its clinical potential and mechanisms of action is still needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platinum complexes in cancer chemotherapy. [2013]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Cis-diamminedichloroplatinum(II). A new antineoplastic agent derived from the group of heavy metal complexes (author's transl)]. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

A strategy for the development of two clinically active cisplatin analogs: CBDCA and CHIP. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

[Second-generation cisplatin analogs]. [2013]

4. China pubmed.ncbi.nlm.nih.gov

[A randomized phase II trial of paclitaxel in combination chemotherapy with platinum in the treatment of non-small cell lung cancer]. [2010]

5. France pubmed.ncbi.nlm.nih.gov

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

[Phase I study of a new antineoplastic agent, cis-diamminedichloroplatinum (II)]. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Platinum complexes in cancer chemotherapy. [2013]

8. Ireland pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and pharmacokinetics of cis-platinum and analogs. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

The mismatch-repair protein hMSH2 binds selectively to DNA adducts of the anticancer drug cisplatin. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

In vitro interactions between platinum analogues in human ovarian-carcinoma cell lines. [2019]

13. Ireland pubmed.ncbi.nlm.nih.gov

Increased in vitro and in vivo sensitivity of BRCA2-associated pancreatic cancer to the poly(ADP-ribose) polymerase-1/2 inhibitor BMN 673. [2017]