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All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Levoleucovorin

Folic Acid

Camptothecin

Vitamin B Complex

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

CT-2106 as 10 minute infusion on days 1, 15 \& 29 of each 42-day cycle

CT-2106

Folinic acid 200 mg IV 1 hour after CT-2106 infusion on days 1, 2, 15, 16, 29 and 30

Folinic acid

5-FU following CT-2106 and folinic acid infusions @ 400 mg/m² IV bolus then 5-FU 600 mg/m² as a 22 hour IV infusion on Days 1, 2, 15, 16, 29, and 30.

5-FU (fluorouracil)

Barone C., M.D.

CT-2106, a camptothecin (CPT) conjugate, is a new generation of topoisomerase I inhibitors designed to deliver higher, more effective chemotherapy to tumor tissue with less toxicity to normal tissues. The objective of this study is to determine the dose limiting toxicities, safety profile and antitumor activity of CT-2016 in combination with 5-FU and folic acid for the treatment of colorectal cancer.

Phase I/II CT 2106 and 5-FU/FA in Colorectal Cancer

Phase I/II Study of CT-2106 in Combination With Infusional 5-fluorouracil/Folinic Acid (5-FU/FA)(de Gramont Schedule) as Second Line in Patients With Metastatic Colorectal Cancer Failing an Oxaliplatin Plus 5-FU/FA Regimen

CTI BioPharma

Igor Gorbatchevsky,M.D.

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Lung Neoplasms

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Small Cell Lung Cancer

Etoposide

Cisplatin

Etoposide phosphate

Belotecan

Enzyme Inhibitors

Topoisomerase I Inhibitors

Belotecan : 0.5mg/㎡/day for Day 1 to 4, repeated every 3 weeks

Etoposide 100mg/㎡/day for Day 1 to 3, repeated every 3 weeks

Cisplatin 60mg/㎡/day for Day 1, repeated every 3 weeks

In-Jae Oh, M.D.,Ph.D.

Belotecan (Camtobell, CKD-602, Chong Kun Dang Pharm., Korea) is a new camptothecin derivative, that exhibits anticancer effects by inhibiting topoisomerase I. The investigators will have a randomized prospective multicenter trial of Belotecan/Cisplatin versus Etoposide/Cisplatin in patients with previously untreated, extensive-stage small cell lung cancer.

Primary endpoints

* to assess Response Rate

Secondary endpoints

* to assess Overall response duration, Time to progression, Overall survival

Trial of Belotecan/Cisplatin in Chemotherapy Naive Small Cell Lung Cancer Patient

A Randomized Prospective Multicenter Trial of Belotecan/Cisplatin Versus Etoposide/Cisplatin in Patients With Previously Untreated, Extensive-stage Small-cell Lung Cancer

Chong Kun Dang Pharmaceutical

Chonnam National University Hospital

Assistant Professor

Namitecan

ST1968 once a week for 2 weeks every 3 weeks (protocol amendment: once every 3 weeks

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ST1968 once a week for 2 weeks every 3 weeks (protocol amendment: once every 3 weeks

ST1968

Dagmar Hess, MD

ST1968 is a novel camptothecin derivative which interacts with topoisomerase I-DNA complex, inducing S-Phase specific cytotoxicity. It is endowed with a potent antitumor activity and an increased Therapeutic Index with respect to the clinically used analogues (i.e.irinotecan and topotecan) in some xenograft models (ovary, colon, head \& neck, cervix). Anti-tumor activity has been also noted in platinum resistant ovarian cell xenografts and in topoisomerase I mutant prostate cell lines. The acceptable toxicity profile in animals and the activity in camptothecin-resistant cell lines make ST1968 a good candidate for clinical trials.

Multicenter, open label, uncontrolled Phase I pharmacokinetic trial to determine the Maximum Tolerated Dose (MTD) of ST1968 given intravenously (I.V.) once every week for 2 consecutive weeks every 3 weeks and the MTD of ST1968 given I.V. once every 3 weeks. A starting dose of 1.5mg/m2 given as a flat dose of 2.5mg is defined, given once on Day 1, Day 8 every 21 Days (D1, D8 Q21D schedule), over 2 h. Starting dose for the Day 1 every 21 Days (D1 Q21D schedule) has to be determined from the MTD of D1, D8 Q21D schedule.

Plasma, urine pharmacokinetics in all patients (minimum of 3 pts for each cohort) during the first cycle of treatment and in at least 6 patients at the Recommended Dose (RD).

During the study any hints of anti-tumor activity will also be evaluated by RECIST criteria.

ST1968 Intravenous (Weekly) in Solid Tumors

Phase I Dose Finding and Pharmacokinetic Study of the Intravenous Camptothecin ST1968 in Patients With Solid Tumors

2/6 patients with a Dose Limiting Toxicity (DLT) at the first cycle (21 days)

safety assessments (routine physical examinations and laboratory evaluations) and severity of adverse events based on the NCI-Common Terminology Criteria for Adverse Events V. 3.0 (NCI-CTCAE)

objective tumor response based on RECIST criteria

Southern Europe New Drug Organization

sigma-tau i.f.r. S.p.A.

Bevacizumab

Irinotecan

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

EZN-2208

Shivaani Kummar, M.D.

Background:

- The anticancer drug bevacizumab works by reducing the formation of new blood vessels in tumors, which can slow or stop the growth of cancer cells and supporting blood vessels. The experimental drug EZN-2208 works by limiting how well cancer cells can divide. Drugs similar to EZN-2208 also work by turning off the production of the HIF protein, which otherwise can help cancer cells to grow even when blood supply is limited. Researchers are interested in determining if EZN-2208 turns off HIF in patient tumors, and whether combining it with bevacizumab is an effective treatment for cancers that have not responded to standard treatment.

Objectives:

- To assess the safety and effectiveness of the combination of EZN-2208 and bevacizumab for solid tumors that have not responded to standard treatment.

Eligibility:

- Individuals at least 18 years of age who have solid tumors that have not responded to standard treatment.

Design:

* Participants will be screened with a full physical examination and medical history, blood and urine samples, and tumor imaging studies.
* Participants will receive EZN-2208 and bevacizumab intravenously on an outpatient basis in 4-week cycles (with the exception of the first cycle, which will be 5 weeks).
* Cycle 1: Participants will receive EZN-2208 once a week for 3 weeks in a row (days 1, 8, and 15), followed by 1 week without the drug. Participants will receive bevacizumab 1 week before EZN-2208 (day - 7) and then 3 weeks later (day 15).
* Subsequent cycles: Participants will receive EZN-2208 once a week for 3 weeks in a row (days 1, 8, and 15), followed by 1 week without the drug. Participants will receive bevacizumab every 2 weeks (days 1 and 15).
* Participants will have clinic visits with physical examinations and blood tests in the first 3 weeks of each cycle. Clinic visits may also include tumor imaging studies and tumor biopsies as directed by the study researchers.
* Participants will continue to take the study drugs for as long as the tumor shrinks or does not grow, and as long as they do not experience intolerable or unsafe side effects from the drugs.

Background

One reason postulated for the limited efficacy of anti-angiogenic or anti-VEGF agents such as bevacizumab is that they cause intra-tumoral hypoxia, resulting in the induction and up-regulation of hypoxia-inducible factors (HIF) such as HIF-1Alpha. These in turn play a central role in tumor progression by acting as master regulators of how cancer cells adapt to hypoxic conditions. HIF-1Alpha therefore represents an attractive target in oncology.

Camptothecin analogues (including SN-38, topotecan, and irinotecan) have been shown to consistently reduce the translation, expression, and transcriptional activity of HIF-1Alpha in vitro and in vivo, and therefore have the potential to inhibit the HIF-1? induction that occurs with anti-angiogenic agents.

The central rationale of this study is that HIF-1alpha induction by bevacizumab will be offset by weekly administration of EZN-2208 (PEGylated SN-38), and that this will result in synergistic anti-tumor effects.

Objectives

Determine the modulation of HIF-1alpha protein (by ELISA) in solid tumors after treatment with EZN-2208 and bevacizumab.

Determine the safety and tolerability of the combination of EZN-2208 and bevacizumab with EZN-2208 administered weekly times 3 (Days 1, 8, and 15) and bevacizumab administered every 2 weeks in 28-day cycles.

Perform correlative studies to assess changes in angiogenesis in tumor tissue.

Evaluate antitumor responses as determined by RECIST.

Eligibility

Adults with histologically documented solid tumors, whose disease has progressed following standard therapy or who have no acceptable standard treatment.

Performance status ECOG 0-2; adequate organ function; life expectancy at least 3 months; no major surgery, radiation or chemotherapy within 4 weeks prior to study enrollment; recovered from toxicities of prior therapies to at least eligibility levels.

Willingness to undergo tumor biopsies for research purposes.

Study Design

This is a single-arm pilot study.

Patients will receive EZN-2208 IV on Day 1, 8, and 15 of a 28-day cycle at a dose of 9 mg/m(2); bevacizumab will be administered IV every 2 weeks at a dose of 5 mg/kg.

For cycle 1: Bevacizumab will be administered on Day -7 (i.e., 1 week prior to EZN-2208) and Day 15.

For subsequent cycles: Bevacizumab will be administered on Day 1 and 15.

EZN-2208 (Pegylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

Pilot Study of Weekly EZN-2208 (Pegylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors

National Cancer Institute (NCI)

Rectal Neoplasms

Herbal and Botanical

Capecitabine

Cola

During Phase Ib, we will evaluate the safety and determine the MTD/RP2D of CRLX101 + capecitabine (Cape) and radiation therapy (XRT) in patients with rectal cancer using the traditional 3+3 dose escalation design. Adverse events (AEs) will be evaluated via the CTCAE version 4.0. Patients in Phase Ib will also be followed for pathological response if they have resectable disease.

In Phase II, CRLX101 will be administered at the RP2D in combination with capecitabine and radiation in patients with locally advanced rectal cancer for a total of 5-6 weeks, depending on the total radiation dose. A total of 3 doses of CRLX101 will be administered every other week. Surgery will take place at least 6 weeks after the completion of chemoradiotherapy.

CRLX101 is an experimental nanoparticle formulation of the anticancer agent camptothecin manufactured by Cerulean Pharma Inc..

CRLX101

Capecitabine is an oral fluoropyrimidine pro-drug, metabolically converted to 5-fluorouracil after administration. It is indicated as adjuvant treatment in patients with stage III colorectal cancer (Dukes' C colon cancer), and as first-line treatment of metastatic colorectal cancer.

This protocol allows physician discretion as to the use of Intensity Modulated Radiation Therapy (IMRT) or 3D conformal planning techniques.

Radiation begins on Day1 of neoadjuvant chemotherapy and continues for 28 (if \<T4) or 30 (T4 disease) consecutive weekdays. Patient will receive 1.8 Gy daily fractions of radiotherapy without a break except for weekends and holidays.

Dose is to be prescribed to an isodose surface that encompasses the planning target volume (PTV) and that satisfies the dose uniformity guidelines below. The minimum dose to PTV 1 and PTV 2 shall be no less than 95% of the protocol specified dose for that volume.

Radiotherapy

Surgery will take place at least 6 weeks post completion of chemoradiotherapy in patients with resectable disease; tissue from surgical resection will be preserved for correlative studies in those patients who do not achieve a pCR.

Surgery

Andrew Wang, MD

This trial will enroll patients with locally advanced rectal cancer (resectable and non-resectable).The phase Ib dose escalation portion of trial is designed to determine the maximum tolerated dose (MTD) of CRLX101 when combined with standard neoadjuvant therapies capecitabine (Cape) and radiation therapy (XRT). CRLX101 is a nanopharmaceutical (NP) formulation of camptothecin. These results will determine the recommended phase II dose (RP2D) for CRLX101 in this setting. The phase II portion of the trial is designed to evaluate the efficacy and safety of CRLX101 at the RP2D, when combined with capecitabine and radiation therapy prior to surgery.

This is an open label, single-arm, multi-center, Phase Ib/II study designed to evaluate CRLX101, which is a NP formulation of camptothecin, dosed in combination with capecitabine and radiation therapy in patients with advanced rectal carcinoma.

The purpose of the Phase Ib portion of this study is to identify the MTD of CRLX101 when added to standard neoadjuvant chemo-radiotherapy. The MTD will be based on the rate of dose-limiting toxicity (DLT) in Phase Ib, and will be assessed via NCI's CTCAE v4.0 toxicity criteria. The MTD will be assigned as the RP2D in this trial.

If CRLX101 can be safely administered in combination with capecitabine and radiation at doses \>/= 9 mg/m\^2 IV in the Phase Ib study, then the trial will proceed to Phase II. Patients in the Phase Ib study will be included in the Phase II outcome analyses when applicable. The phase II study is designed to evaluate the efficacy of this regimen by assessing the rate of pathological complete response (pCR) while monitoring safety and tolerability.

We anticipate accrual of up to 25 patients per year for the Phase II study, with a slightly faster accrual of 2-3 patients per month for Phase Ib given the broader inclusion criteria.

During Phase Ib, we will evaluate the safety and determine the MTD/RP2D of CRLX101 + capecitabine (Cape) and radiation therapy (XRT) in patients with rectal cancer using the traditional 3+3 dose escalation design. Adverse events (AEs) will be evaluated via the CTCAE version 4.0. Patients in Phase Ib will also be followed for pathological response if they have resectable disease.

If CRLX101 can be safely administered in combination with capecitabine and radiation at doses \>/=9 mg/m\^2 IV in the Phase Ib study, then the trial will proceed to Phase II with a primary objective of estimating the rate of pCR. Non-metastatic patients with resectable disease and treated at the MTD/RP2D in Phase Ib will be included in the Phase II study population.

In Phase II, CRLX101 will be administered at the RP2D in combination with capecitabine and radiation in patients with locally advanced rectal cancer for a total of 5-6 weeks, depending on the total radiation dose. A total of 3 doses of CRLX101 will be administered every other week. Surgery will take place at least 6 weeks after the completion of chemoradiotherapy.

For our non-metastatic Phase I patients and our Phase II population, postoperative adjuvant therapy is indicated regardless of whether a pCR is achieved or not. While there are a number of regimens used in the adjuvant setting, national guidelines do not specify one of these regimens over the other. Given the consistent application of adjuvant therapies in this population, we also plan to follow Phase II patients for both disease free survival (DFS) and overall survival (OS).

Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Rectal Cancer

Phase Ib/II Study of Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Locally Advanced Rectal Cancer

The MTD is the highest dose of CRLX101 at which ≤1 out of 6 patients had a dose limiting toxicity (DLT) using CTCAE v4.0 toxicity criteria. DLTs include Grade (G) \>3 neutropenia for ≥7 days; G 3 or 4 neutropenia with fever; G 4 anemia not related to cancer-associated bleeding; G 4 thrombocytopenia or G 3 with clinically significant bleeding; G ≥3 nausea or vomiting \>48 hours despite anti-emetics; G 2 cystitis not resolved within 14 days; second G 2 cystitis; G 3 or 4 cystitis; diarrhea requiring dose reduction; Any other non-hematologic toxicity G ≥3 requiring a dose reduction (G ≥3 infusion-related reactions were not a DLT unless they recur despite slowing down the infusion); Other CRLX101 related treatment emergent adverse effect (TEAE) that requires patient withdrawal prior to completing all doses; Radiotherapy interruption due to TEAEs ≥5 days; or Dose interruption or reduction of capecitabine due to TEAE that results in \<50% of the scheduled capecitabine dose for entire course

Primary Objective Phase II: Pathological response will be made based on microscopic assessment of the surgical specimen at the primary treatment site. A pCR must include no gross or microscopic tumor identified anywhere within the surgical specimen. This must include:No evidence of malignant cells in the primary tumor specimen and No lymph nodes that contain tumor.

Pathologic response will be made based on microscopic assessment of the surgical specimen at the primary treatment site, including regional nodes and any peritumoral satellite nodules in the specimen, and categorized as outlined below as per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 7th edition.Determination of pathological response will be reported by the local pathologist.

* Pathologic Complete Response (pCR): No gross or microscopic tumor identified anywhere within the surgical specimen. This must include: No evidence of malignant cells in the primary tumor specimen and No lymph nodes that contain tumor.
* Moderate response: Single cells or small groups of cancer cells
* Minimal response: Residual cancer outgrown by fibrosis
* Poor response:Minimal or no tumor kill; extensive residual cancer

Toxicity profile of CRLX101 when combined with capecitabine + radiotherapy to treat patients with locally advanced rectal cancer. Phase Ib and Phase II - Safety is the reported adverse event (AE) profile characterized by NCI CTCAE v4.0. The profile was limited to grade 3 or higher, treatment related AEs.

Phase II only - DFS will be defined as the time from surgical resection until disease recurrence or death as a result of any cause, reported as the count of participants still alive without recurrence at the end of study follow-up.

Phase II only - OS is defined as the time from surgical resection until death reported as the count of participants still alive at the end of study follow-up.

Phase II only - a comparison of DFS for patients who achieve pCR and those who do not. DFS will be defined as the time from surgical resection until disease recurrence or death as a result of any cause, reported as the count of participants still alive without recurrence at the end of study follow-up.

Phase II only - a comparison of OS for patients who achieve pCR and those who do not. OS is defined as the time from surgical resection until death reported as the count of participants still alive at the end of study follow-up.

Cerulean Pharma Inc.

UNC Lineberger Comprehensive Cancer Center

All patients were evaluated for serious adverse events (SAEs)

12mg/m\^2 CRLX101 every other week + 825mg/m\^2 BID Capecitabine + XRT

Cohort A, Phase Ib, Level 1

15mg/m\^2 CRLX101 every other week + 825mg/m\^2 BID Capecitabine + XRT

Cohort A, Phase Ib, Level 2

15mg/m\^2 CRLX101 IV weekly + 825mg/m\^2 BID Capecitabine + XRT

Cohort A, Phase II, Level 2

12mg/m\^2 CRLX101 IV weekly + 825mg/m\^2 BID Capecitabine + XRT

Cohort B, Phase Ib, Level 1

Cohort B, Phase Ib, Level 2

CRLX101 12mg/ m\^2 , via intravenous catheter (IV), on Monday, every other week for the first five weeks of chemoradiation.

Capecitabine 825mg/ m\^2 by mouth two times a day (PO BID), Monday through Friday (M-F) XRT 180 centigray (cGy)/day, M-F for 6 weeks

Cohort A, Phase Ib, Dose Level 1

CRLX101 15mg/ m\^2 , via intravenous catheter (IV), on Monday, every other week for the first five weeks of chemoradiation.

Capecitabine 825mg/ m\^2 PO BID, M-F XRT 180 cGy/day, M-F for 6 weeks

Cohort A, Phase Ib, Dose Level 2

Cohort A, Phase II, Dose Level 2

CRLX101 12mg/ m\^2 , via intravenous catheter (IV), on Monday, every week for the first five weeks of chemoradiation.

Capecitabine 825mg/ m\^2 PO BID, M-F XRT 180 cGy/day, M-F for 6 weeks

Cohort B, Phase Ib, Dose Level 1, Weekly

CRLX101 15mg/ m\^2 , via intravenous catheter (IV), on Monday, every week for the first five weeks of chemoradiation.

Capecitabine 825mg/ m\^2 PO BID, M-F XRT 180 cGy/day, M-F for 6 weeks

Cohort B, Phase Ib, Dose Level 2, Weekly

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Follow-up of participants was ended early, resulting in few or no observed events (progression or death) for all survival endpoints.

Robin Johnson

Phase Ib patients who received at least one dose of CRLX101 at either 12mg/m2 or 15mg/m2 either every other week (Cohort A) or weekly (Cohort B)

Dose Escalation Phase Ib

Since this objective applies only to Phase Ib patients, the Phase II cohort patients were not included

Maximum Tolerated Dose (MTD) of CRLX101 When Added to Standard Neoadjuvant Chemoradiotherapy Consisting of Capecitabine + Radiotherapy in Locally Advanced Rectal Cancer

All resectable participants who received CRLX101 + capecitabine (Cape) and radiation therapy (XRT) regardless of dose and timing of treatment

All Participants

Pathological Complete Response (pCR) Rate

Pathological Response Rate

Colitis

Dermatitis, radiation

Diarrhea

Hypophosphatemia

Lymphocyte count decreased

Rectal obstruction

White blood cell decreased

Number of Participants With Grade 3 or Higher, Treatment-related Toxicities

14 of 32 participants were enrolled in the Phase II portion of the study. Of these 14, one participant withdrew prior to surgery and was therefore not evaluable for this outcome

Disease-free Survival (DFS) Rate

Overall Survival (OS) Rate

pathological complete response (pCR)

Did not achieve pCR

Disease-free Survival (DFS) Rate Based on Pathological Complete Response (pCR).

Overall Survival (OS) Based on Pathological Complete Response (pCR).

CRLX101 12mg/ m\^2 , via intravenous catheter (IV), on Monday, every other week for the first five weeks of chemoradiation.

Capecitabine 825mg/ m\^2 PO BID, M-F XRT 180 cGy/day, M-F for 6 weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I/II CT 2106 and 5-FU/FA in Colorectal Cancer	NCT00291785	Colorectal Canc...	CT-2106 Folinic acid 5-FU (fluoroura...	18 Years -	CTI BioPharma
Trial of Belotecan/Cisplatin in Chemotherapy Naive Small Cell Lung Cancer Patient	NCT00826644	Carcinoma, Smal...	Belotecan Etoposide Cisplatin	19 Years - 80 Years	Chonnam National University Hospital
Trial of Belotecan/Cisplatin in Chemotherapy Naive Small Cell Lung Cancer Patient	NCT00826644	Carcinoma, Smal...	Belotecan Etoposide Cisplatin	19 Years - 80 Years	Chonnam National University Hospital
Trial of Belotecan/Cisplatin in Chemotherapy Naive Small Cell Lung Cancer Patient	NCT00826644	Carcinoma, Smal...	Belotecan Etoposide Cisplatin	19 Years - 80 Years	Chonnam National University Hospital
ST1968 Intravenous (Weekly) in Solid Tumors	NCT01748019	Solid Tumors	ST1968	18 Years -	sigma-tau i.f.r. S.p.A.
EZN-2208 (Pegylated SN-38) in Combination With Bevacizumab in Refractory Solid Tumors	NCT01251926	Neoplasms	EZN-2208 Bevacizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Neoadjuvant Chemoradiotherapy With CRLX-101 and Capecitabine for Rectal Cancer	NCT02010567	Rectal Cancer	CRLX101 Capecitabine Radiotherapy Surgery	18 Years -	UNC Lineberger Comprehensive Cancer Center

Spots Global Cancer Trial Database for camptothecin

Every month we try and update this database with for camptothecin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.