CBP501 + Cisplatin + Nivolumab for Pancreatic Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of different combinations of three drugs—CBP501 (an experimental treatment), cisplatin, and nivolumab—in treating advanced exocrine pancreatic cancer. The goal is to assess the effectiveness and tolerability of these drug combinations for patients who have already undergone other treatments. Eligible participants have stage IV exocrine pancreatic cancer, have completed at least two previous treatment rounds, and have a white blood cell count under 10,000/mm³. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of CBP501, cisplatin, and nivolumab is generally safe for treating advanced pancreatic cancer. Studies indicate that patients tolerate this treatment well without severe problems.

Research also shows that the combination of CBP501 and cisplatin alone is both safe and effective.

Previous studies have noted some common side effects, such as vomiting, with cisplatin and nivolumab together, and less often, more serious issues like infections. However, this treatment is generally considered safe, especially since both drugs are already approved for other types of cancer.

Overall, the safety data for these treatments are promising, with studies reporting manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced pancreatic cancer because they combine CBP501, a novel agent, with standard drugs like Cisplatin and Nivolumab to potentially enhance cancer-fighting effects. Unlike traditional chemotherapy options that primarily target rapidly dividing cells, CBP501 may work by modifying the tumor environment to increase cancer cells' sensitivity to chemotherapy. This unique approach aims to improve the overall efficacy of the treatment, offering hope for better outcomes compared to current therapies. The combination could also leverage the immune-boosting capabilities of Nivolumab, giving the body's own defenses a better chance to fight the cancer.

What evidence suggests that this trial's treatments could be effective for stage IV exocrine pancreatic cancer?

Research has shown that combining CBP501, cisplatin, and nivolumab yields promising results for advanced pancreatic cancer. In this trial, some participants will receive this combination, which early findings suggest benefits patients who haven't responded to other treatments. Previous patients found the side effects manageable. Other participants will receive different combinations, such as CBP501 with cisplatin or cisplatin with nivolumab. Earlier trials confirmed that patients responded well to these treatments. Additionally, nivolumab and cisplatin together have improved survival rates in other cancers, suggesting potential effectiveness for pancreatic cancer as well. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• CBP501
• Cisplatin
• Nivolumab

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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]

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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38422585/

A multicenter, randomized phase 2 study to establish ...

This study aimed to (1) confirm efficacy of CBP501/cisplatin/nivolumab for metastatic PDAC observed in a previous phase 1 study, (2) identify combinations that ...

2.

ejcancer.com

ejcancer.com/article/S0959-8049(24)00126-6/fulltext

A multicenter, randomized phase 2 study to establish ...

Safety and efficacy results, based on the 3MPFS primary endpoint, suggested the combination of 25 mg/m2 CBP501 + 60 mg/m2 cisplatin + 240 mg ...

3.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(23)03411-7/fulltext

1625P Multicenter, randomized, parallel group, phase II ...

Preliminary results indicate clinically meaningful improvement and tolerable safety of CBP501, cisplatin and nivolumab as 3rd line treatment for metastatic PDAC ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04953962

NCT04953962 | Study of CBP501/Cisplatin/Nivolumab ...

This design yields a type I error rate of 2.5% and power of 80% when the true percentage of patients progression-free at 3 months is 35%. Official Title.

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3059

Phase Ib clinical study of CBP501, cisplatin, and nivolumab ...

We report safety and efficacy outcomes from dose-escalation and expansion cohorts of a Phase Ib study of CBP501 combined with cisplatin and nivolumab.

6.

withpower.com

withpower.com/trial/phase-3-pancreatic-neoplasms-8-2021-d836b

Study of CBP501/Cisplatin/Nivolumab Combinations in ...

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 ...