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Three treatment cycles, intravenous infusion of Promitil

Patients treated with the selected RP2D of PROMITIL (3 mg/kg) intravenously administered on their first cycle and reduced dose of 2 mg/kg from cycle 2 and onwards.

Only for mCRC patients.

Patients treated with one cycle of 2.5mg/kg Promitil day 1 together with Capecitabine 1,000 mg bid po days 1-21 followed by two cycles of 2.0 mg/kg Promitil day 1 together with Capecitabine 1,000 mg bid po days 1-21, at four-week intervals.

Only for mCRC patients.

Patients treated with one cycle of 2mg/kg Promitil I.v and 5 mg/kg Bevacizumab i.v on day 1 together with Capecitabine 1,000 mg bid p.o days 1-14 at four-week intervals.

Only for mCRC patients.

Patients treated with one cycle of 2mg/kg Promitil I.v and 7.5 mg/kg Bevacizumab i.v on day 1 together at three-week intervals.

Only for mCRC patients.

Promitil

1000 mg dose BID PO for days 1-21 for Combination Cohort and on day 1-14 on Triple combination Cohort

for Triple combination cohort an IV dose of 5 mg/kg on day 1 at 4 week interval. For the 3 weekly cohort an IV dose of 7.5 mg/kg at 3 week interval.

This is a Phase I, multi-center, Dose-Escalating, Safety Study of an Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer Patients with Solid Tumors. The study comprised of:

Escalated cohorts A-H: 27 male or female participants, ages 18-80, BMI 18-36 diagnosed with inoperable, recurrent or metastatic malignant solid tumors, deemed incurable, and who have failed to respond to standard therapy or for whom no standard therapy is available. Eligible subjects will be assigned, successively in order of accrual, to one of eight cohorts, to receive escalating doses of intravenously infused PROMITIL. PROMITIL will be administered as an intravenous infusion. Dose escalation will only proceed in the absence of dose-limiting toxicity (DLT). For this purpose, each cohort will only begin its first cycle of PROMITIL when the cohort preceding it has successfully completed its first 4-week cycle without any signs of DLT.

Expanded cohort: 17 adult patients with metastatic CRC. The purpose of this expanded cohort is to further evaluate the safety of Promitil and to search for signs of antitumor activity of Promitil in this specific patient population.

Combination Cohort (Promitil concomitantly with Capecitabine): 23 adult patients with metastatic CRC.

Triple combination Cohort: 13 additional subjects with metastatic CRC, received combination of Promitil concomitantly with Bevacizumab (5 mg/kg) on day 1 of a 28 day cycle and Capecitabine on days 1-14 of a 28 day cycle.

3 weekly cohort- 9 subjects with metastatic CRC will receive Promitil and Bevacizumab (7.5 mg/kg) on day 1 of a 21 day cycle.

For all cohorts, PROMITIL will be administered as an intravenous infusion at an initial rate of 0.25mg/min followed by gradual increase to a maximal rate of 2mg/min until completion of dosing, if absence of infusion reactions is established and in line with most updated version of IFU available for this study.

For each subject, subsequent dosing will take place 28 days after the previous treatment, provided they are deemed fit to be dosed again.

Patients will return to the study center on days 8, 15, 22 of cycle 1, and on day 15 of cycles 2 and 3, for monitoring assessments.

All patients will be followed-up for survival and post-Promitil treatment. Patients who did not received 3 cycles of PROMITIL will be followed up only until PD.

For the 3 weekly cohort Promitil will be administered at 3 week interval together with Bevacizumab (7.5 mg/kg). Patients will return to the study center on days 8 and 15 of cycle 1, and on day 15 of cycles 2 and 3, for monitoring assessments.

Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PROMITIL) in Cancer Patients With Solid Tumors.

A Phase I, Dose-Escalating, Safety Study of an Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, PROMITIL) in Cancer Patients With Solid Tumors.

Only DLTs occurring during the first cycle of treatment for each participant will determine MTD endpoint

PK assessments will monitor plasma levels of MLP and metabolite (MMC), as well as PK parameters (Cmax, AUC0-t, AUC 0-∞, MRT, t½ , Kel, Cl, VD).

Lipomedix Pharmaceuticals Inc.

DCBCI0901 7.5mg/m2, iv infusion for day 1-day 5 and day 15-day 20

DCBCI0901 7.5mg/m2 iv infusion for day 1 to day 5 and day 15 to day 20

DCBCI0901

Chia-Chi Lin, Ph.D.

* Investigate the safety and tolerability of multiple DCBCI0901 infusions in patients with advanced solid tumor
* Pharmacokinetic parameters will be calculated for DCBCI0901, if data permit.
* Anti tumor activity: The efficacy endpoint will be the overall response rate (ORR) defined as the proportion of patients who continuously receive treatment after Cycle 1 with a best overall response of complete response (CR) or partial response (PR).

This is a Phase I, open label, first in human study designed to evaluate the safety, tolerability and PK of escalating doses of DCBCI0901 in patients with advanced solid tumors. Each treatment cycle will be 28 days in duration with no gap between cycles. During each cycle, DCBCI0901 will be administered slowly as a 30 minute intravenous (IV) infusion (use of infusion pump preferred) once daily (QD) in the first 5 day dosing period (Days 1 to 5), which will be followed by 9 days of recovery and observation (Days 6 14). DCBCI0901 will be administered intravenously QD in a second 5 day dosing period (Days 15 through 19), followed again by 9 days of recovery and observation (Days 20 through 28).

Patients may continue to receive treatment in 28 day cycles after completion of Cycle 1. To qualify for continued treatment beyond Cycle 1, all of the following criteria must be fulfilled:

* The patient is willing to receive further treatment
* Toxicity induced by the IP is not considered to be unbearable as judged by the Investigator
* The patient does not have PD as defined by Response Evaluation Criteria in Solid Tumors
* The patient satisfies the criteria for dosing
* The patient does not meet any of the criteria for withdrawal

After the first cycle, CT/MRI assessment will be performed once every 8 weeks (2 cycles) for efficacy evaluation, or per Investigator judgment. After the first year of treatment, the Investigator will assess the patient using CT/MRI based on his/her discretion.

Safety data will be evaluated according to normal practice.

Upon discontinuation of study treatment (if applicable), assessments for the Early termination visit (if discontinuation occurs in Cycle 1) or End of Treatment visit (if discontinuation occurs in Cycle 2 or onwards) should occur within 3 days of discontinuation. Assessments for the Follow up visit (10 days \[±1 day\] after the last dose of IP) and End of Study (EOS) visit (30 days \[±3 days\] after the last dose of IP)

Safety, Tolerability and Pharmacokinetics of DCBCI0901 in Patients With Advanced Solid Tumor

Phase I, Sequential Dose Escalation Clinical Study to Investigate the Safety, Tolerability and Pharmacokinetics of in Patients With Advanced Solid Tumor

The efficacy endpoint will be the overall response rate (ORR) defined as the proportion of patients who continuously receive treatment after Cycle 1 with a best overall response of complete response (CR) or partial response (PR).

AE and SAE, physical examination, vital signs, weight, clinical laboratory examinations (hematology, blood chemistry, blood coagulation, and urinalysis), pulmonary function tests, pulse oximetry, and ECGs. Adverse events and SAEs will be collected from the time of informed consent, throughout the study, until the EOS visit or up to 1 year of treatment.

Pharmacokinetic parameters will be determined from DCBCI0901 plasma concentrations using noncompartmental methods. DCBCI0901 PK parameters to be calculated (if adequate data are available for estimation) will include Cmax, time to Cmax (tmax), applicable AUC parameters such as AUC from time zero to the last quantifiable time point (AUC(0 last)), AUC from time zero to infinity (AUC(0 inf)), and/or AUC over the dosing interval tau (AUC(0 tau)), terminal half life (t1/2), systemic clearance (CL), steady state volume of distribution and volume of distribution in the terminal phase (Vss and Vz, respectively), and multiple/single dose accumulation parameters for Cmax and AUC (RCmax and RAUC).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Intravenously Administered Pegylated Liposomal Mitomycin-C Lipid-based Prodrug (PROMITIL) in Cancer Patients With Solid Tumors.	NCT01705002	Cancer Solid Tumor Metastatic Colo...	Promitil Capecitabine Bevacizumab	18 Years - 80 Years	Lipomedix Pharmaceuticals Inc.
Safety, Tolerability and Pharmacokinetics of DCBCI0901 in Patients With Advanced Solid Tumor	NCT02151357	Cancer	DCBCI0901	20 Years - 80 Years	Standard Chem. & Pharm. Co., Ltd.

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