Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Subcutaneous dose of dalantercept once every 3 weeks.

Dalantercept

Dalantercept, a soluble form of the activin receptor-like kinase-1 protein, is being studied in patients with squamous cell carcinoma of the head and neck (SCCHN). Dalantercept blocks the development of blood vessels that supply tumors.

For cancer cells to grow, they need to have nutrients supplied to them through blood vessels. The study drug, dalantercept, is designed to work by blocking the growth of those blood vessels and preventing cancer cells from growing. The purpose of this study is to find out if dalantercept can cause SCCHN tumors to shrink or stop growing. This study will also evaluate the safety of dalantercept in patients with SCCHN.

Study of Dalantercept in Patients With Squamous Cell Carcinoma of the Head and Neck

An Open-label Phase 2 Study of Dalantercept in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

ORR is defined as the proportion of patients who met criteria for complete response or partial response. Patients were evaluable for ORR if they had at least one measurable lesion at baseline and at least one disease assessment after baseline. RECIST version 1.1 was used to evaluate efficacy. In addition, patients who developed clinical or radiological progression of disease prior to the scheduled tumor assessment were also considered evaluable for response. The response rate was estimated as the proportion of patients evaluable for response who meet the criteria for complete (CR) and partial response (PR). Per RECIST v1.1 for target lesions and assessed by MRI: complete response (CR), disappearance of all target lesions; partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR + PR.

Number of participants with at least one adverse event as a measure of safety and tolerability.

Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is AUC0-t (cycle 1).

Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is Cmax (cycle 1).

PFS is defined as the date of the first dose to the first observation of disease progression (according to RECIST v.1.1) or death due to any cause. Progression is defined using RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

OS is calculated as the number of months from date of the first dose to the date of death. The last patient treated will be followed for overall survival for 1 year following treatment initiation.

Disease control rate will be estimated as the proportion of patients evaluable for response who meet the criteria for complete response, partial response, or stable disease.

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

Subcutaneous 80 mg dose of dalantercept once every 3 weeks.

Dalantercept 80 mg

Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.

Dalantercept 0.6 mg/kg

Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.

Dalantercept 1.2 mg/kg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Senior Vice President, Global Clinical Development

Subcutaneous 0.6-mg/kg dose of dalantercept once every 3 weeks.

Subcutaneous 1.2-mg/kg dose of dalantercept once every 3 weeks.

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol had been amended to incorporate weight-based dosing for the remainder of the study population. 40 received at least one dose of study drug in either the 0.6 mg/kg or 1.2 mg/kg dose groups and had at least one on-treatment tumor assessment.

Objective Response Rate (ORR)

Safety and Tolerability

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol was amended to incorporate weight-based dosing for the remainder of the study population. 2 patients in the 0.6-mg/kg and 6 in the 1.2-mg/kg cohort had less than 2 measurable serum dalantercept concentrations and were excluded from PK analysis.

Dalantercept Serum Concentration After Single and Multiple Doses

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol had been amended to incorporate weight-based dosing for the remainder of the study population.

Progression Free Survival (PFS)

Overall Survival (OS)

Disease Control Rate

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Disease Attributes

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

All Drugs and Chemicals

Antibodies

Immunoglobulins

Immunoglobulins, Intravenous

Immunoglobulin Fc Fragments

Immunologic Factors

Patients receive dalantercept SC on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Robert A Burger

This phase II trial studies the side effects and how well dalantercept works in treating patients with ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer that has returned. Dalantercept may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Dalantercept may also stop the growth of tumor cells by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial) in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, treated with dalantercept.

II. To determine the frequency and severity of adverse events associated with treatment with dalantercept as assessed by the Active Version of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

SECONDARY OBJECTIVES:

I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

TERTIARY OBJECTIVES:

I. To measure the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-B), activin receptor-like kinase 1 (ALK1), cluster of differentiation 105 (CD105), and other markers via immunohistochemistry (IHC) and determine if there is correlation between expression and clinical response to treatment.

II. To determine the correlation between ALK1 gene expression, other markers, and clinical response to treatment.

III. To determine the correlation between concentration of VEGF, bone morphogenetic protein (BMP)9, BMP10, and ALK1 in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay (ELISA), and clinical response to treatment.

OUTLINE:

Patients receive dalantercept subcutaneously (SC) on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Dalantercept in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

A Phase II Evaluation of Dalantercept (NSC #757172), a Novel Soluble Recombinant Activin Receptor-Like Kinase 1 (ALK-1) Inhibitor Receptor-Fusion Protein, in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Associated with measures of clinical response to treatment, including PFS and OS.

Percentage of participants who survive progression-free for at least 6 months without non-protocol therapy after study entry. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.

Number of participants with a maximum grade of 3 or higher during the treatment period.

Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.

National Cancer Institute (NCI)

Gynecologic Oncology Group

Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg\*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.

\*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.

30-39 years

40-49 years

50-59 years

60-69 years

70-79 years

Age, Customized

Angela Kuras on behalf of Wei Deng, PhD

Progression-free for at Least 6 Months Without Non-protocol Therapy From Study Entry

Neutropenia

Other Investigations

Cardiac disorders

Gastrointestinal disorders

General disorders and administration site conditio

Infections and infestations

Metabolism and nutrition disorders

Musculoskeletal and connective tissue disorders

Renal and urinary disorders

Reproductive system and breast disorders

Respiratory, thoracic and mediastinal disorders

Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 4.0

Objective Tumor Response

Overall Survival

Progression-free Survival

Gene Expression Levels of ALK1 and Other Markers

IHC Expression Levels of VEGF, FGF, TGFB, ALK1, CD105 and Other Markers

Pre-treatment Plasma Concentration Levels of VEGF, BMP9, BMP10, and ALK1

Adenocarcinoma

Carcinoma, Transitional Cell

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Transitional Cell Carcinoma

Adenocarcinoma of the Appendix

Patients receive dalantercept SC on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Vicky Makker

This phase II trial studies how well dalantercept works in treating patients with endometrial cancer that has come back or is persistent. Dalantercept may stop the growth of endometrial cancer by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To estimate the proportion of patients with persistent or recurrent endometrial cancer who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with dalantercept (ACE-041).

II. To determine the nature and degree of toxicity of dalantercept in this cohort of patients.

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent endometrial cancer treated with dalantercept.

TERTIARY OBJECTIVES:

I. To measure the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), activin receptor-like kinase 1 (ALK1), endoglin (CD105), and other markers via immunohistochemistry (IHC) and determine if there is correlation between expression and clinical response to treatment.

II. To determine the correlation between ALK1 gene expression, other markers, and clinical response to treatment.

III. To determine the correlation between concentration of VEGF, bone morphogenetic protein 9 (BMP9), bone morphogenetic protein 10 (BMP10), and ALK1 in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay (ELISA), and clinical response to treatment.

IV. To correlate somatic mutations in candidate genes with response to therapy.

OUTLINE:

Patients receive dalantercept subcutaneously (SC) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Dalantercept in Treating Patients With Recurrent or Persistent Endometrial Cancer

A Phase II Evaluation of Dalantercept, a Novel Soluble Recombinant Activin Receptor-Like Kinase 1 (ALK-1) Inhibitor Receptor-Fusion Protein, in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Response was defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and based on imaging done every other cycle. Responses can be either partial or complete. Per RECIST v1.1 target and non-target lesions are assessed by MRI or CT scan: Complete Response (CR), Disappearance of all target and non-target lesions and all lymph nodes must be \< 10 mm in short axis; Partial Response (PR), \>=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD.

Treatment and Progression-free Survival is defined as the duration alive from study entry until progression is documented, death or non-protocol treatment is initiated; whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

Non-protocol treatment initiation prior to disease progression and prior to 6 months from study entry was counted as an event for treatment and progression-free survival at 6 months. Disease progression within 6 months of study entry or death within 6 months of study entry and prior to disease progression counts as an event for treatment and progression-free survival at 6 months.

Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

Disease progression within 6 months of study entry or death within 6 months of study entry and prior to disease progression counts as an event for progression-free survival at 6 months.

Progression-free survival is defined as the duration alive from study entry until progression is documented or death, whichever comes sooner. Progressive disease is defined as at least a 5 mm absolute increase and a 20% relative increase in the sum of measurable target lesions' longest dimensions relative to the smallest sum at baseline or on study or the appearance of new lesions or unequivocal progression of existing non-target lesions.

Duration of survival is defined as the duration alive from study entry until death or last contact.

The frequencies of the maximum grade of any acute adverse event, regardless of attribution are reported during treatment and up to 30 days after stopping the study treatment are reported.

The frequencies of the maximum grade of any serious adverse event or all other adverse events by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported

Dalantercept 1.2 mg/kg (maximum starting dose of 120 mg) subcutaneously once every three weeks. One cycle is defined as three weeks.

Patients weighing more than 100 kg start treatment at 120 mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.

A CT of the chest, abdomen and pelvis to assess response by RECIST 1.1 is required every two cycles. Treatment was to continue until disease progression or adverse effects prohibit further therapy.

Patients receive dalantercept SC on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Dalantercept: Given SC

Laboratory Biomarker Analysis: Correlative studies

Treatment (Dalantercept)

40-49

50-59

60-69

70-79

Linda Gedeon, BA, CCRP Clinical Research Coordinator

Response

Treatment and Progression-free Survival at 6 Months

Progression-free Survival at 6 Months

Duration of Progression-free Survival

Duration of Survival

Anemia

Abdominal Distention

Abdominal Pain

Ascites

Constipation

Diarrhea

Gastric Hemorrhage

Nausea

Rectal Fistula

Rectal Hemorrhage

Vomiting

Edema Face

Edema Limbs

Fatigue

Prolonged activated partial thromboplastin time

Alkaline Phosphatase Increased

Creatinine Increased

Lymphocyte Count Decreased

Weight Loss

Anorexia

Dehydration

Hyperglycemia

Hypoalbuminemia

Hypoglycemia

Hypokalemia

Arthralgia

Back Pain

Myalgia

Dizziness

Headache

Neuralgia

Urinary Tract Obstruction

Dyspnea

Epistaxis

Pleural Effusion

Hypertension

Thromboembolic Event

Number of patients who did not experience the specified AE.

Grade 0

Number of patients who experienced a grade 1 event using Common Terminology Criteria version 4.0

Grade 1 (CTCAE v4.0)

Number of patients who experienced a grade 2 event using Common Terminology Criteria version 4.0

Grade 2 (CTCAE v4.0)

Number of patients who experienced a grade 3 event using Common Terminology version 4.0

Grade 3 (CTCAE v 4.0)

Number of patients who experienced a grade 4 event using Common Terminology Criteria version 4.0

Grade 4 (CTCAE v 4.0)

Number of patients who experienced a grade 5 event using Common Terminology Criteria version 4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Dalantercept in Patients With Squamous Cell Carcinoma of the Head and Neck	NCT01458392	Squamous Cell C...	Dalantercept	18 Years -	Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Dalantercept in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer	NCT01720173	Recurrent Fallo... Recurrent Ovari... Recurrent Prima...	Dalantercept Laboratory Biom...	18 Years -	GOG Foundation
Dalantercept in Treating Patients With Recurrent or Persistent Endometrial Cancer	NCT01642082	Endometrial Ade... Endometrial Cle... Endometrial Mix... Endometrial Muc... Endometrial Ser... Endometrial Squ... Endometrial Tra... Endometrial Und... Recurrent Uteri...	Dalantercept Laboratory Biom...	18 Years -	GOG Foundation

Spots Global Cancer Trial Database for dalantercept

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