CClinicalTrials.gg
CompletedNCT03494166Updated Oct 19, 2023Results posted

Post-chemotherapy Symptom Management SMART

An interventional study of Start with SMSH+TIPC and Start with SMSH alone in Cancer, sponsored by University of Arizona. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-19.

Sponsored by University of Arizona · Not applicable, Interventional, and Supportive care

Phase
Not applicable
Study type
Interventional
Enrollment
498
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Survivors of solid tumors (N=451) who completed curative intent chemotherapy for a solid tumor within the past 2 years were interviewed at baseline and stratified as high or low need for symptom management based on comorbidity and depressive symptoms.

High need survivors were randomized initially to the 12-week Symptom Management and Survivorship Handbook (SMSH, N=282) or 12-week SMSH Telephone Interpersonal Counseling (TIPC, N=93) added during weeks 1-8. After 4 weeks of the SMSH alone, non-responders on depression were re-randomized to continue with SMSH alone (N=30) or add TIPC (N=31).

Read the detailed description

Nearly 15.5 million Americans have survived cancer and virtually all have experienced symptoms from cancer treatment. Numerous symptom management interventions have been tested during active treatment, yet few have addressed the continuing fatigue, pain, depression, etc. that endure following the end of treatment.

Existing post-treatment symptom management research has targeted survivors months after the end of active treatment, overlooking the immediate post-treatment period. During this period, some survivors have their symptoms resolve naturally (low need for intervention), while others suffer from high symptom burden (high need for intervention), with 30% experiencing depression. Sample: Survivors of solid tumors (N=451) who completed curative intent chemotherapy for a solid tumor within the past 2 years.

Design: The SMART design incorporates two interventions with proven efficacy and addresses heterogeneity of survivors' responses by following the clinical logic of starting with one intervention, assessing its success, and continuing it when effective. High need survivors will be initially randomized to receive 1) weekly symptom assessment with referral for elevated symptoms to a printed Symptom Management and Survivorship Handbook (SMSH) or 2) a more intensive intervention adding Telephone Interpersonal Counselling (TIPC) to the SMSH. After 4 weeks, non-responders to SMSH alone on depression were re-randomized to continue SMSH for 8 more weeks to allow for symptom resolution, or TIPC added for the remaining 8 weeks.

The primary outcome was symptom severity index, secondary outcome was depressive symptoms. The hypotheses tests included comparisons of primary and secondary outcomes according tp first randomization and second randomization for non-responders.

02

Conditions studied

  • Cancer

Keywords

  • Chemotherapy, symptom management
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Survivors must have a new diagnosis or localized recurrence of solid tumor cancer
  • Be finishing curative intent adjuvant chemotherapy or chemoradiation, and do not have any subsequent cancer treatments planned, except for radiation therapy, hormonal therapy or trastuzumab for breast cancer.
  • 18 years of age or older
  • Have access to a telephone
  • Understand English or Spanish
  • Are not currently receiving counseling and/or psychotherapy

Exclusion criteria

Exclusion Criteria:

  • Diagnosis of a psychotic disorder in medical record verified by the recruiter
  • Nursing home resident
  • Bedridden
  • Currently receiving counseling and/or psychotherapy.
04

Study design

Phase
Not applicable
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Single (Outcomes assessor)
Enrollment
498 participants (actual)

Study arms

  • No intervention
    Low Need Benchmark or Follow-up

    In the low need benchmark or follow-up group, survivors completed detailed baseline and 13-week assessments (about 30-40 minutes) over the telephone. A brief assessment (about 5 minutes) at week 4 over the telephone was used to assess symptoms.

  • Experimental
    High Need A: Start with SMSH alone for 4 weeks

    Participants were mailed the printed Symptom Management and Survivorship Handbook (SMH). The Group A participant was called every week for 4 weeks to ask about symptoms and suggest strategies from the SMH to relieve symptoms. After 4 weeks, participants were re-randomized to continue in SMH for 8 more weeks or to add Telephone Interpersonal Counseling (TIPC) Intervention for the subsequent 8 weeks. If the TIPC was added, the counselor called the participant once per week for about 35-40 minutes to assess and discuss interpersonal relationships, communication, social support, managing symptoms and survivorship. At week 13, the participant completed the second assessment.

    Behavioral: Start with SMSH alone

  • Experimental
    High Need B: Start with SMSH+TIPC

    Participants were called every week for the first 8 weeks using a combination of TIP-C and SMH. The counselor called to assess and discuss interpersonal relationships, communication, social support, managing symptoms and survivorship. At the end of 8 weeks, the final 4 calls followed the SMSH alone protocol. At week 13, the second assessment was conducted.

    Behavioral: Start with SMSH+TIPC

Interventions

  • BehavioralStart with SMSH+TIPC

    See arm/group descriptions

  • BehavioralStart with SMSH alone

    See arm/group descriptions

05

What researchers measure

Primary outcomes

  1. Symptom Severity Index- Comparison of Two Groups Created by First Randomization

    Symptoms were measured using the modified General Symptom Distress Scale (GSDS) allowing for a quick assessment of 18 symptoms: fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicated the severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 1-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, with higher score indicating worse outcome (greater severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable.

    Time frame: Weeks 1-13

  2. Symptom Severity Index- Comparison of Two Groups Created by Second Randomization

    Symptoms were measured using the modified General Symptom Distress Scale (GSDS) allowing for a quick assessment of 18 symptoms: fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicated severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 5-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, higher value reflect worse outcome (greater symptom severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable.

    Time frame: Weeks 5-13

Secondary outcomes

  1. Depressive Symptoms- Comparison of Two Groups Created by First Randomization.

    Measured using Center for Epidemiological Studies-Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms).

    Time frame: Week 13

  2. Depressive Symptoms - Comparison of Two Groups Created by Second Randomization

    Measured using Center for Epidemiological Studies-Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms).

    Time frame: Week 13

06

Results

Posted Oct 19, 2023
Limitations and caveats
The larger than anticipated proportion of high need survivors resulted in a larger sample size for tests of hypotheses associated with first randomization. The higher than anticipated response rate to the SMSH at week 4 resulted in a lower number of survivors in the second randomization compared to the requirements of power analysis. On the other hand, a higher than anticipated rate of response to the SMSH alone led to a larger than planned number of responders.

Participant flow

Cancer survivors were recruited at a comprehensive cancer center, a federally qualified health center, and community settings in the Southwestern United States. Participants were informed they would be 1) randomized to SMSH or TIPC+SMSH and may be rerandomized after 4 weeks to continue with SMSH alone or add TIPC; 2) telephone assessment and intervention sessions were weekly for 13 weeks; 3) interventions were designed to help reduce symptoms and there were study incentives.

Participant flow — Overall Study
MilestoneLow Need Benchmark or Follow-upHigh Need- SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12Drop-outs From SMSH Alone Prior to Week 4
Started7120430319317
Completed581952823720
Not completed139282117
Withdrew: Death000130
Withdrew: Lost to follow-up2222140
Withdrew: Withdrawal by subject10705317
Withdrew: Screen failure100010

Outcome measures

PrimarySymptom Severity Index- Comparison of Two Groups Created by First Randomization

Symptoms were measured using the modified General Symptom Distress Scale (GSDS) allowing for a quick assessment of 18 symptoms: fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicated the severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 1-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, with higher score indicating worse outcome (greater severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable.

Time frame:
Weeks 1-13
Reported as:
Least squares mean · score on a scale
Symptom Severity Index- Comparison of Two Groups Created by First Randomization
score on a scaleHigh Need A; Start With SMSH AloneHigh Need B: Start With SMSH+TIPC
Symptom Severity Index- Comparison of Two Groups Created by First Randomization24.53 ± 0.6825.86 ± 1.15
Statistical analysis
  • High Need A; Start With SMSH Alone vs High Need B: Start With SMSH+TIPC · Mixed Models Analysis · p = .31 (P-value was not adjusted for multiple comparisons. A priori threshold for statistical significance was set at .05.) · Mean difference (final values): -1.31 · 95% CI -3.90 to 1.25The mean of the group that started with SMSH alone minus the mean of the group that started with SMSH+TIPC (average over time).
PrimarySymptom Severity Index- Comparison of Two Groups Created by Second Randomization

Symptoms were measured using the modified General Symptom Distress Scale (GSDS) allowing for a quick assessment of 18 symptoms: fatigue, sleep difficulties, pain, headache, difficulty concentrating, lack of appetite, nausea, vomiting, constipation, diarrhea, numbness or tingling, skin rashes or sores, swelling, weakness, shortness of breath, cough, depression, and anxiety. Respondents indicated severity of each symptom (0 = not present to 10 = worst possible). A summed symptom severity index for 17 symptoms other than depression was averaged over weeks 5-13 from each weekly contact, baseline, and 13-week interviews. Potential range 0-170, higher value reflect worse outcome (greater symptom severity). Because the collection of symptoms does not form a scale, internal consistency reliability was not applicable.

Time frame:
Weeks 5-13
Reported as:
Least squares mean · score on a scale
Symptom Severity Index- Comparison of Two Groups Created by Second Randomization
score on a scaleContinue With SMSH Alone After Week 4Add TIPC to SMSH After Week 4
Symptom Severity Index- Comparison of Two Groups Created by Second Randomization35.94 ± 2.3838.11 ± 2.49
Statistical analysis
  • Continue With SMSH Alone After Week 4 vs Add TIPC to SMSH After Week 4 · Mixed Models Analysis · p = .52 (The p-value was not adjusted for multiple comparisons. A priori threshold for statistical significance was .05.) · Mean difference (final values): -2.18 · 95% CI -8.91 to 4.55The mean of the group that continued with SMSH alone minus the mean of the group that had TIPC added to the SMSH after week 4.
SecondaryDepressive Symptoms- Comparison of Two Groups Created by First Randomization.

Measured using Center for Epidemiological Studies-Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms).

Time frame:
Week 13
Reported as:
Least squares mean · score on a scale
Depressive Symptoms- Comparison of Two Groups Created by First Randomization.
score on a scaleHigh Need A-SMSH or TIP-CHigh Need B-TIP-C+SMSH
Depressive Symptoms- Comparison of Two Groups Created by First Randomization.11.89 ± .5512.30 ± .99
Statistical analysis
  • High Need A-SMSH or TIP-C vs High Need B-TIP-C+SMSH · Regression, Linear · p = .71 (P-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was .05.) · Median difference (final values): -0.41 · 95% CI -2.63 to 1.81The mean of group that started with SMSH alone minus the mean of the group that started with SMSH+TIPC.
SecondaryDepressive Symptoms - Comparison of Two Groups Created by Second Randomization

Measured using Center for Epidemiological Studies-Depression (CES-D) 20-item scale. Potential score range is 0-60. Higher scores indicated worse outcome (higher depressive symptoms).

Time frame:
Week 13
Reported as:
Least squares mean · score on a scale
Depressive Symptoms - Comparison of Two Groups Created by Second Randomization
score on a scaleContinue With SMSH Alone After Week 4Add TIPC to SMSH After Week 4
Depressive Symptoms - Comparison of Two Groups Created by Second Randomization16.05 ± 1.9316.81 ± 2.11
Statistical analysis
  • Continue With SMSH Alone After Week 4 vs Add TIPC to SMSH After Week 4 · Regression, Linear · p = .79 (P-value was not adjusted for multiple comparisons. The a priori threshold for statistical significance was .05.) · Mean difference (final values): -0.76 · 95% CI -6.53 to 5.01The mean of the group that continued with SMSH alone minus the mean of the group that had TIPC added to the SMSH after week 4.

Adverse events

Collected over Each participant was assessed for adverse events at baseline (week 0) and weekly for 13 weeks or up until their attrition date if applicable.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Low Need Benchmark or Follow-up0/71 (0%)0/71 (0%)0/71 (0%)
High Need A-SMH or TIP-C1/282 (0.4%)0/282 (0%)0/282 (0%)
High Need B-TIP-C+SMH3/93 (3.2%)0/93 (0%)0/93 (0%)

Baseline characteristics

Of 500 individuals who consented, 451 completed a baseline and 5 were ineligible.

Age, Continuous
Age, Continuous(years)Low Need Benchmark or Follow-upHigh Need-SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12Drop-outs From SMSH Alone Prior to Week 4Total
Mean53.56 ± 13.1358.76 ± 12.3160.63 ± 12.8853.83 ± 15.3158.26 ± 12.9360.18 ± 9.0457.67 ± 12.73
Sex/Gender, Customized
Sex/Gender, Customized(Participants)Low Need Benchmark or Follow-upHigh Need-SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12Drop-outs From SMSH Alone Prior to Week 4Total
Male22324614280
Female4917225257815364
Other0010001
Missing0000101
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Low Need Benchmark or Follow-upHigh Need-SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12Drop-outs From SMSH Alone Prior to Week 4Total
American Indian or Alaska Native0010102
Asian1002328
Black or African American3001206
White3612119145611257
More than one race1002306
Unknown or not reported30831012284167
Hispanic or Latino39921313458210
Not Hispanic or Latino321111718489235
Unknown0100001
Symptom Severity
Symptom Severity(units on a scale)Low Need Benchmark or Follow-upHigh Need-SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12Drop-outs From SMSH Alone Prior to Week 4Total
Mean24.70 ± 20.3536.32 ± 25.4846.97 ± 22.8148.13 ± 26.4637.28 ± 24.6556.06 ± 34.1836.96 ± 24.85
Depressive Symptoms
Depressive Symptoms(units on a scale)Low Need Benchmark or Follow-upHigh Need-SMSH Alone for 4 Weeks, Depression Responders Continued With SMSH Alone for Weeks 5-12High Need-SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH Alone for Weeks 5-12High Need- SMSH Alone for 4 Weeks, Depression Non-responders Continued With SMSH+TIPC for Weeks 5-12High Need- SMSH+TIPC During Weeks 1-8 Followed by SMSH Alone During Weeks 9-12Drop-outs From SMSH Alone Prior to Week 4Total
Mean6.01 ± 4.6613.01 ± 11.0823.35 ± 12.6923.72 ± 2.7216.36 ± 13.4219.25 ± 13.7214.28 ± 11.92
07

Study locations

2 sites
  • Cancer Center at St. Joseph's
    Phoenix, Arizona 85004, United States
  • University of Arizona
    Tucson, Arizona 85721, United States
08

References and documents

Publications

  • Sikorskii A, Badger T, Segrin C, Crane TE, Chalasani P, Arslan W, Hadeed M, Morrill KE, Given C. A Sequential Multiple Assignment Randomized Trial of Symptom Management After Chemotherapy. J Pain Symptom Manage. 2023 Jun;65(6):541-552.e2. doi: 10.1016/j.jpainsymman.2023.02.005. Epub 2023 Feb 17. PubMed 36801353 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 10, 2021
  • Informed consent form · Dec 14, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — We will share the findings and data with other researchers, the public, and key stakeholders based on the principles that NIH has articulated regarding the sharing of study results and resources. The University of Arizona agrees that data sharing is essential for expedited translation of research results into knowledge, products, and procedures to improve health. Sharing of study results Manuscript based on results from the proposed study will be published in peer-reviewed journals. We will select "open access" options for these manuscripts whenever possible. Data Sharing Data from this study will be available to other researchers under the following conditions: 1) appropriate human subjects protection is in place; 2) data have been de-identified; and 3) study investigators have publicly presented and published key findings. Data and safety monitoring plan is described under Human Subjects.

Supporting information: Study protocol, Sap

09

Registry details

Key details

Study ID
NCT03494166
Lead sponsor
University of Arizona
Collaborators
Michigan State University, National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 11, 2018
Start date
Jul 1, 2018
Primary completion
Jun 3, 2022
Completion
Jun 3, 2022
Results posted
Oct 19, 2023
Last update
Oct 19, 2023

Study contacts

Terry Badger, PhD
principal investigator · University of Arizona

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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