Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Digestive System Diseases

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Prostatic Neoplasms

Neoplasm Metastasis

Stomach Neoplasms

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Head and Neck Neoplasms

Stomach Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Taxane

Altretamine

CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks).

CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) with the option to administer G-CSF in cycle one. Starting dose will be 45 mg/m2.

CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with taxane naïve advanced solid tumors of gastric, head and neck, lung, and ovarian.

CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with taxane naïve advanced breast cancer.

CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with taxane naïve advanced prostate cancer.

CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) at the recommended Phase 2 dose (X mg/m2) in 15 patients with either ovarian or/and breast cancer who have failed prior taxane treatment (ie, either progressed on a taxane regimen or within 6 months of receiving a taxane regimen).

CPO-100

Study Officials

Christopher Lim

Ingrid Palma, MHS

AnaArlene SJ Ramirez, RN, OCN

Ashley McClain Wallace

Cancer Answer Line

Joanathan Huntzinger

Carrie Friedman

This is a Phase 1, multicenter, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) in adult patients with advanced solid tumors.

The study has three parts. Part A-1 is a dose-escalation phase with a modified "3+3" design in patients with metastatic or unresectable advanced solid tumors to evaluate the safety, tolerability and pharmacokinetics (PK) as a single agent. Two patients will be enrolled at each of the first 2 dose levels and observed for safety during the first cycle. If there are no ≥Grade 2 treatment emergent adverse events (TEAE) that are clinically significant and attributed to the study drug as assessed by the investigator during Cycle 1 for any of the patients in the first two dose levels, the 3rd dose level and beyond will follow the traditional 3+3 design. Dose escalation during the "3+3" period for each subsequent cohort of patients will be guided by the incidence of CPO-100-related adverse events (AE) as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) CTCAE v5.0 in the first 4 weeks of dosing \[the Dose Limiting Toxicity (DLT) evaluation period\].

In Part A-2, the starting dose for this part will be 45 mg/m2. This dose was established in Part A-1 as being that dose at which the use of Granulocyte-colony stimulating factor ()G-CSF is indicated given that the only Grade 3 treatment-related adverse events noted were related to neutropenia and was well managed with G-CSF support. Prophylactic use of G-CSF will be permitted in Cycle 1 based on the investigator judgement.

This additional intervention of primary prophylaxis will be explored in order to determine if the risk of febrile neutropenia (FN) under these circumstances is reduced. Dose escalation during the 3+3 period for each subsequent cohort of patients will be guided by the incidence of CPO-100-related adverse events (AE) as graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in the first 4 weeks of dosing (the DLT evaluation period).

After the Maximum Tolerated Dose (MTD) of weekly dosing schedule has been established, a recommended Phase 2 dose will be selected based on evaluation of the PK, and safety and tolerability profile on all available Part A study data by the Safety Review Committee (SRC). The selection of the Recommended Phase 2 Dose (RP2D) will consider all available clinical and non-clinical CPO-100 data as well as relevant docetaxel published data.

Part B expansion phase will further evaluate the safety and tolerability as well as the preliminary antitumor activity at the selected RP2D. Four cohorts of patients are included in Part B:

* Cohort 1: taxane naïve advanced/metastatic gastric, head and neck, lung, and ovarian cancers
* Cohort 2: taxane naïve advanced/metastatic breast cancer
* Cohort 3: taxane naïve advanced /metastatic prostate cancer
* Cohort 4: advanced/metastatic breast or ovarian cancer who have either progressed on a taxane or have developed progressive disease within 6 months of receiving a taxane.

The taxane naïve patient population is defined as patients who have not received taxane or taxane-based therapies for their metastatic diseases or patients who had suboptimal taxane exposure defined as having received less than 2 cycles of taxane or taxane-based therapies due to intolerability for their metastatic diseases. Patients who have received taxane or taxane-based therapies for their neoadjuvant treatment or patients who have received taxane or taxane-based therapies for their adjuvant treatment without disease progression during treatment are also considered taxane naïve, as long as they have not received taxane or taxane-based therapies to treat the metastatic diseases.

It is estimated that approximately 60 patients can be enrolled in Parts A-1 and A-2. The exact number of patients will depend on the number of dose levels tested. A total of 60 patients, 15 patients in each cohort will be enrolled in Part B.

The total duration of the study is estimated to be approximately 5 years. Patients may continue receiving CPO-100 until criteria for withdrawal are met. Patients deriving clinical benefit may continue to receive study medication for as long as they are benefiting from treatment. In the event the study closes or terminates while patients are still benefiting from and receiving CPO-100, every effort will be made to continue drug supply.

Modified "3+3" dose escalation design followed by dose expansion at the MTD (maximum tolerated dose).

Dose Escalation and Dose Expansion Study of CPO-100 in Patients With Advanced Solid Tumors

A Phase 1, Multicenter, Single Agent Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of CPO-100 in Adult Patients With Advanced Solid Tumors

Incidence of dose-limiting toxicities (DLT) during the DLT evaluation period. DLTs assessed per CTCAE v5.0, include grade ≥ 4 neutropenia, thrombocytopenia, anemia; grade ≥ 3 febrile neutropenia, nausea, vomiting, diarrhea, skin rash, fatigue, infusion reaction; any other grade ≥ 2 non-hematologic toxicity judged to be dose limiting; and treatment delay \>14 days due to unresolved toxicities.

Incidence and severity of Adverse Events per CTCAE v5.0, including changes of Clinical Laboratory Values, Physical Exams, Vital Signs, Weight, Eastern Cooperative Oncology Group (ECOG) and ECG from baseline. Dosing delays and dosing intensity.

Area under the plasma concentration curve (AUC0-t) will be from time zero to last quantifiable concentration.

Area under the plasma concentration curve (AUC0-∞) will be from time zero to infinity.

Cmax will be estimated from the maximum post-dose concentration recorded for each patient.

Tmax will be estimated from the relative time of the maximum post-dose concentration recorded for each patient.

The proportion of patients achieving a partial response (PR) or complete response (CR) per RECIST 1.1 supplemented by recommendations from the Prostate Cancer Clinical Trials Working Group 3 (PCCTWG3).

The proportion of patients achieving a stable disease (SD), PR, CR per RECIST 1.1 supplemented by recommendations from the Prostate Cancer Clinical Trials Working Group 3 (PCCTWG3).

Time from first PR or CR until progression of death using definition of PR and CR per (RECIST) 1.1 supplemented by recommendations from the Prostate Cancer Clinical Trials Working Group 3 (PCCTWG3).

Time from first dose until disease progression or death using RECIST 1.1 supplemented by recommendations from the Prostate Cancer Clinical Trials Working Group 3 (PCCTWG3) for progression.

Spots Global Cancer Trial Database for taxane naïve