Trial Outcomes & Findings for Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia (NCT NCT00003702)

Last Updated: 2018-05-15

Results Overview

Primary outcome is measured as a difference in proportion responding between treatment arms and evaluated using a chi square test. A complete response was defined as a normal hCG sustained over four weekly measurements.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

240 participants

Primary outcome timeframe

Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months.

Results posted on

2018-05-15

Participant Flow

This trial opened to patient accrual on 6/14/1999 and closed to accrual on 2/26/2007.

Participant milestones

Participant milestones
Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks
Overall Study STARTED	120	120
Overall Study COMPLETED	107	109
Overall Study NOT COMPLETED	13	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks
Overall Study Ineligible cell types	2	2
Overall Study Did not meet criteria for persistence	8	5
Overall Study WHO score > 6	2	1
Overall Study Inadequate documentation of disease	1	3

Baseline Characteristics

Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly n=107 Participants Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks n=109 Participants Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks	Total n=216 Participants Total of all reporting groups
Age, Continuous	28.8 years STANDARD_DEVIATION 7.9 • n=93 Participants	30.4 years STANDARD_DEVIATION 8.6 • n=4 Participants	29.6 years STANDARD_DEVIATION 8.3 • n=27 Participants
Sex: Female, Male Female	107 Participants n=93 Participants	109 Participants n=4 Participants	216 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Endpoint was assessed by hCG measurements taken weekly, once normal, treatment was bi-weekly, then monthly, up to 12 months.

Population: Eligible patients who received a random treatment allocation

Outcome measures

Outcome measures
Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly n=107 Participants Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks n=109 Participants Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks
Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay Complete/Cure	57 Participants	76 Participants
Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay Non-response	48 Participants	29 Participants
Response Based on Blood Human Chorionic Gonadotropin (hCG) Assay Inevaluable	2 Participants	4 Participants

PRIMARY outcome

Timeframe: Prior to study entry, weekly during treatment, up to 12 months after normal titer, an average of 7 months.

Population: Eligible and treated patients

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

Outcome measures

Outcome measures
Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly n=107 Participants Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks n=109 Participants Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0	14 Participants	20 Participants

SECONDARY outcome

Timeframe: Prior to study entry and on Day 1 of treatment

Population: Eligible and evaluated patients

Number of patients with a decline in hCG on day 1 of treatment relative to the level at enrollment. A decline is defined as a decrease by 1 or more units between enrollment and treatment start.

Outcome measures

Outcome measures
Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly n=178 Participants Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks
Number of Patients With a Decline of hCG on Day 1 of Treatment	72 Participants	—

Adverse Events

Arm 1: Methotrexate 30 mg/m2 IM Weekly

Serious events: 0 serious events

Other events: 50 other events

Deaths: 0 deaths

Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks

Serious events: 1 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly n=107 participants at risk Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks n=107 participants at risk Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.

Other adverse events

Additional Information

Angela M. Kuras on behalf of Virginia Filiaci

NRG Oncology

Phone: 7168455702

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm 1: Methotrexate 30 mg/m2 IM Weekly n=107 participants at risk Arm 1: Methotrexate 30 mg/m2 IM weekly	Arm 2: Dactinomycin 1.25 mg/m2 IV Push Every 2 Weeks n=107 participants at risk Arm 2: Dactinomycin 1.25 mg/m2 IV push every 2 weeks
Blood and lymphatic system disorders Leukopenia	2.8% 3/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	6.5% 7/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Blood and lymphatic system disorders Neutropenia	5.6% 6/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	18.7% 20/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Blood and lymphatic system disorders Thrombocytopenia	1.9% 2/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Blood and lymphatic system disorders Anemia	6.5% 7/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	13.1% 14/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Blood and lymphatic system disorders Other Hemotologic	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Immune system disorders Allergy	1.9% 2/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Ear and labyrinth disorders Auditory	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Cardiac disorders Cardiovascular	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	1.9% 2/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Vascular disorders Coagulation	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
General disorders Constitutional	11.2% 12/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	14.0% 15/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Skin and subcutaneous tissue disorders Dermatologic	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Endocrine disorders Endocrine	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	1.9% 2/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Gastrointestinal disorders Gastrointestinal	6.5% 7/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	13.1% 14/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Gastrointestinal disorders Nausea	7.5% 8/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	19.6% 21/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Gastrointestinal disorders Vomiting	2.8% 3/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	13.1% 14/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Gastrointestinal disorders Diarrhea	1.9% 2/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Gastrointestinal disorders Stomatitis	4.7% 5/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Renal and urinary disorders Genitourinary/Renal	2.8% 3/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Blood and lymphatic system disorders Hemorrhage	8.4% 9/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	12.1% 13/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Hepatobiliary disorders Hepatic	1.9% 2/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	2.8% 3/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Infections and infestations Infection/Fever	6.5% 7/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	3.7% 4/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Metabolism and nutrition disorders Metabolic	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	1.9% 2/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Musculoskeletal and connective tissue disorders Musculoskeletal	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Nervous system disorders Neurologic	5.6% 6/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	4.7% 5/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Eye disorders Ocular/Visual	4.7% 5/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	3.7% 4/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
General disorders Pain	12.1% 13/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	13.1% 14/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Respiratory, thoracic and mediastinal disorders Pulmonary	0.00% 0/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	7.5% 8/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.
Reproductive system and breast disorders Sexual	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.	0.93% 1/107 • Through Study completion, an average of 7 months. The frequencies of any serious adverse event or other adverse events (grade 2 or higher) by category or specific term occurring during treatment and up to 30 days after stopping the study treatment are reported. Adverse events were collected by Organ System Class.