Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Irinotecan

Fluorouracil

Cisplatin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Orally twice a day for 14 days (dosage will vary)

Continuous infusion 24 hours a day for 14 days (Days 1-14) Dosage will vary

5-Fluorouracil (5-FU)

Intravenously weekly for 2 weeks (given after cisplatin) followed by a one-week rest period

Intravenously weekly for 2 weeks followed by a one week rest period

Peter C. Enzinger, MD

The purpose of this study is to test the safety of irinotecan and cisplatin in combination with either capecitabine or continuous infusion 5-fluorouracil and to see what effects (good and bad) these have on patients with unresectable, advanced solid tumors.

* This is a Phase I dose escalation study. The dose of drug the patient receives will be assigned based upon when they enter the study. Since we are looking for the highest dose of capecitabine or 5-fluorouracil that can be given safely in combination with cisplatin and irinotecan, not everyone who participates in this study will be receiving the same amount of the drug.
* There are four parts to this study: 1)Choice of treatment, 2)Evaluation, 3)Chemotherapy and 4)Follow-up.
* The patient and the patient's doctor will decide which form of chemotherapy is best for the patient, either pill form or continuous infusion. Chemotherapy pills (capecitabine) are given twice per day for 14 days is a row every 3 weeks. Continuous infusion (5-fluorouracil) is given through a pump 24 hours a day for 14 days every 3 weeks.
* Prior to initiation to therapy the extent of the patients cancer will be evaluated. This includes a CT scan, chest x-ray, EKG and bloodwork.
* Patient's will receive chemotherapy for 2 weeks followed by a one week break. This will constitute one cycle. The medications cisplatin and irinotecan will be given intravenously on the 1st and 8th day of each cycle. Following the rest period the next cycle of chemotherapy begins.
* Following 2 cycles of chemotherapy, the patients cancer will be re-evaluated. A CT scan and bloodwork will be obtained and will be compared to the previous studies. Treatment will resume if the cancer is the same size or smaller than before and the patient is tolerating the chemotherapy well. The cancer will be re-evaluated every 2 cycles of chemotherapy.

Capecitabine or 5-Fluorouracil in Combination With Irinotecan and Cisplatin in Patients With Solid Tumor Malignancies

A Phase I Trial of Capecitabine or Continuous Infusion 5-Fluorouracil in Combination With Weekly Irinotecan and Cisplatin in Patients With Advanced Solid Tumor Malignancies

Brigham and Women's Hospital

Massachusetts General Hospital

Dana-Farber Cancer Institute

Principal Investigator

Docetaxel

Tubulin Modulators

Antimitotic Agents

Given intravenously on days 1 and 8 of a 21-day cycle. Participants can continue to receive study drug as long as there disease does not worsen and they do not experience serious side effects.

Taxotere

CPT-11

Charles S. Fuchs, MD

The purpose of this study is to find the highest dose of the combination of taxotere, cisplatin and CPT-11, that can be given without causing severe side effects. We also want to test the safety of this drug combination and see what effects (good and bad) it has on patients with advanced cancer for which there is no known curable treatment.

* This is a Phase I clinical trial. We are unsure of the safest and most effective dose of the drugs and therefore are planning on treating 3-6 patients with a given dose before increasing to higher dose levels.
* Each patient will receive approximately two cycles of therapy. On day one and day eight, they will receive taxotere, cisplatin and CPT-11 intravenously. The cycle will begin again on day 22.
* The following tests and procedures will be performed: CAT scan prior to beginning therapy, after every 2 cycles of therapy, and at the end of the study; physical exam before each course of therapy; vital signs before and with each dose of therapy; routine blood tests before starting therapy and weekly during treatment; chest x-ray and echocardiogram before starting therapy and; toxicity assessment each week of therapy.
* Patients will remain on the study as long as their cancer responds to treatment and they do not have unacceptable side effects.

Taxotere, Cisplatin, and CPT-11 in Advanced Solid Tumor Malignancies

Phase I Study of Taxotere, Cisplatin, and CPT-11 in Advanced Solid Tumor Malignancies

CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off

CRLX301

Elizabeth Dees, MD

A Phase 1/2a, open-label, dose-escalation study with enrollment in Phase 1 to continue until determination of the Maximum Tolerated Dose (MTD) /Recommended Phase 2a Dose (RP2D), and then enrollment into Phase 2a expansion cohorts will be initiated.

Phase 1 is an open-label, dose-escalation protocol. It is anticipated that up to 36 patients will be enrolled in Phase 1. All patients will be assigned to treatment with CRLX301 as the single agent.

For the first 2 cohorts a 1+5 study design will be utilized. A single patient will be enrolled sequentially into cohort 1 and cohort 2. If either patient in cohort 1 or 2 experiences a dose limiting toxicity (DLT) during Cycle 1, then the cohort will be expanded to enroll additional patients up to a total of 6.

As of cohort 3 and for all subsequent cohorts, a 3+3 dose escalation schema will be utilized.

MTD/RP2D will be determined at the dose level when \<2 of 6 patients experience a DLT in a cohort.

The Phase 2a part of the study will be an open-label expansion cohort study. An additional 24 patients with advanced, histologically confirmed solid tumor malignancies will be enrolled. All patients will be assigned to treatment at the MTD/RP2D with CRLX301 as the single agent.

All patients will be followed for safety, tumor response, and progression free survival (PFS) all per RECIST version 1.1 guidelines. Patients will remain on study treatment until they experience progression of disease, unacceptable toxicity, or other specified reason for discontinuation.

Phase 1 dose escalation study followed by phase 2a expansion cohort

Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumors

Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumor Malignancies

Determination of MTD is dependent upon number of dose limiting toxicities and significant adverse events observed.

Safety variables will include AEs, SAEs, Severe AEs, Related AEs and AEs leading to Discontinuation in phase 2a subjects.

Area under the concentration vs time curve of released docetaxel in blood and/or urine specimens of patients receiving at least 1 dose of CRLX301.

Best overall tumor response will be provided per dose cohort using RECIST 1.1

NewLink Genetics Corporation

CRLX301 7.5 mg/m2 IV given every 3 weeks

CRLX301

Schedule 1 Cohort 1

CRLX301 15 mg/m2 IV given every 3 weeks

CRLX301

Schedule 1 Cohort 2

CRLX301 30 mg/m2 IV given every 3 weeks

CRLX301

Schedule 1 Cohort 3

CRLX301 60 mg/m2 IV given every 3 weeks

CRLX301

Schedule 1 Cohort 5

CRLX301 75 mg/m2 IV given every 3 weeks

CRLX301

Schedule 1 Cohort 6

CRLX301 90 mg/m2 IV given every 3 weeks

CRLX301

Schedule 1 Cohort 7

CRLX301 25 mg/m2 IV given weekly

CRLX301

Schedule 2 Cohort 1

CRLX301 35 mg/m2 IV given weekly

CRLX301

Schedule 2 Cohort 2

CRLX301 45 mg/m2 IV given weekly

CRLX301

Schedule 2 Cohort 3

CRLX301 54 mg/m2 IV given weekly

CRLX301

Schedule 2 Cohort 4

CRLX301 54 mg/m2 given weekly for 3 weeks with 1 week off

CRLX301

Schedule 2 Cohort 5

CRLX301 75mg/m2 IV given every 3 weeks

CRLX301

Phase 2a Expansion Cohort

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Primary Site of Disease at Study Entry

Patients were assessed by systemic assessment using the ECOG performance scale. All patients had to be 0 or 1 for inclusion in the study. ECOG performance score of 0 = Fully active, able to carry on all pre-disease performance without restriction. ECOG performance score of 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, etc.

Baseline ECOG Status

Baseline BMI (kg/m^2)

Manager, Clinical Operations

At least one TEAE

At least one Serious TEAE

At least one DLT

At least one severe TEAE

At least one related TEAE

At least one TEAE leading to discontinuation

The phase 1 safety population were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study.

Number of Phase 1 Participants With Treatment Emergent Adverse Events and Dose Limiting Toxicities

The safety population (all patients) were analyzed for dose limiting toxicities and treatment emergent adverse events. Treatment totals include all patients that received the specific dose at any point during the study.

Number of Phase 2a Participants With Adverse Events as a Measure of Safety and Tolerability

Evaluate the Pharmacokinetic (PK) Profile of CRLX301

Complete Response

Partial Response

Stable Disease

Progressive Disease

Not Evaluated

All patients treated on study (safety population) were evaluated for overall tumor response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Capecitabine or 5-Fluorouracil in Combination With Irinotecan and Cisplatin in Patients With Solid Tumor Malignancies	NCT00215501	Solid Tumor	Capecitabine 5-Fluorouracil ... Irinotecan Cisplatin	18 Years -	Dana-Farber Cancer Institute
Capecitabine or 5-Fluorouracil in Combination With Irinotecan and Cisplatin in Patients With Solid Tumor Malignancies	NCT00215501	Solid Tumor	Capecitabine 5-Fluorouracil ... Irinotecan Cisplatin	18 Years -	Dana-Farber Cancer Institute
Capecitabine or 5-Fluorouracil in Combination With Irinotecan and Cisplatin in Patients With Solid Tumor Malignancies	NCT00215501	Solid Tumor	Capecitabine 5-Fluorouracil ... Irinotecan Cisplatin	18 Years -	Dana-Farber Cancer Institute
Taxotere, Cisplatin, and CPT-11 in Advanced Solid Tumor Malignancies	NCT00251407	Solid Tumor	Taxotere Cisplatin CPT-11	18 Years -	Dana-Farber Cancer Institute
Phase 1/2a Dose-Escalation Study of CRLX301 in Patients With Advanced Solid Tumors	NCT02380677	Advanced Solid ...	CRLX301	18 Years -	Lumos Pharma

Spots Global Cancer Trial Database for advanced solid tumor malignancy