Study of CBP501 + Pemetrexed + Cisplatin in Patients With Solid Tumors (Phase I) and Patients With Malignant Pleural Mesothelioma (Phase II)

Primary Outcome Measures:

• Ph I: To determine the MTD of CBP501 + pemetrexed + cisplatin in patients with advanced solid tumors. Ph II: To evaluate the efficacy and safety profile of CBP501 + pemetrexed + cisplatin in patients with malignant pleural mesothelioma [ Time Frame: End of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

• Ph I: To determine the recommended CBP501 dose for exploration in the phase II part [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
• Ph I: To undertake a preliminary characterization of the safety profile of the triplet combination [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
• Ph I: Determine the pharmacokinetics of CBP501 when co-administered with cisplatin and pemetrexed and investigate any potential interactions [ Time Frame: End of study ] [ Designated as safety issue: No ]
• Ph I: To evaluate the pharmacodynamics of the triplet combination [ Time Frame: End of study ] [ Designated as safety issue: No ]
• Ph II: To characterize the efficacy according to Modified RECIST criteria, of cisplatin combined with pemetrexed in this patient population and to aid in formulation of the hypothesis for an eventual phase III trial [ Time Frame: End of study ] [ Designated as safety issue: No ]
• Ph II: To evaluate clinical benefit of patients [ Time Frame: End of study ] [ Designated as safety issue: Yes ]
• Ph II: To evaluate the pharmacodynamics of the combination [ Time Frame: End of study ] [ Designated as safety issue: No ]
• Ph II: Determine the pharmacokinetics of CBP501 when co-administered with cisplatin and pemetrexed and investigate any potential interactions (only in cycle 1 of the first 6 patients in each arm in the US only) [ Time Frame: End of study ] [ Designated as safety issue: No ]

Eligibility Criteria

Inclusion Criteria:

1. Signed informed consent obtained prior to initiation of any study-specific procedures
2. Phase I: Histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective or would otherwise be eligible for cisplatin and pemetrexed as first-line therapy
   Phase II: Histologically or cytologically confirmed diagnosis of malignant pleural mesothelioma (MPM), not amenable for radical resection, who has not received previous chemotherapy or other systemic treatment
3. Measurable disease according to the modified Response Evaluation Criteria in Solid Tumors (RECIST, see below)
4. Male or female patients aged at least 18 years
5. ECOG Performance Status (PS): 0-2
6. Previous anticancer treatment must be discontinued at least 3 weeks prior to first dose of study treatment (6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, with the exception of 8 weeks for bicalutamide)
7. Life expectancy greater than 3 months
8. Adequate organ function
9. Female patients of child-bearing potential must have a negative pregnancy test and be using at least one form of contraception as approved by the Investigator for 4 weeks prior to the study and 4 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 one year or are surgically sterile”
10. Male patients must use a form of barrier contraception approved by the investigator during the study and for 4 months after the last dose of study drug
11. Ability to cooperate with the treatment and follow-up

Exclusion Criteria:

1. Radiation therapy to more than 30% of the bone marrow prior to entry into the study
2. Phase II only: Mesothelioma originating outside the pleura (e.g.: peritoneum)
3. Absence of measurable lesions
4. The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator.
5. Any previous history of another malignancy within 5 years of study entry (other than cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix)
6. Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient’s compliance
7. Evidence of peripheral neuropathy > grade 1 according to NCI-CTCAE Version 3
8. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to study entry
9. Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception
10. Known HIV, HBV, HCV infection
11. Presence of CNS metastases